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Entry
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- *300841 - COAGULATION FACTOR VIII; F8
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*300841</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#history">History</a>
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</li>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/300841">Table View</a>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000185010;t=ENST00000360256" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=2157" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=300841" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000185010;t=ENST00000360256" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000132,NM_019863" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000132" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=300841" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.proteinatlas.org/search/F8" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/31499,119767,182317,182383,182803,182818,579768,2196906,3421393,4503647,4582649,5739349,7544140,7544142,7544144,10518506,18490690,31746297,39963662,56385012,68534650,81170802,83627910,83627916,83627922,83627928,83627934,83627945,83627951,83627957,83627963,83627969,83627975,83627981,83627987,83627993,83627999,83628005,83628011,83628017,83628023,83628029,83628035,83628041,83628047,83628053,83628059,83628065,83628071,83628077,83628083,83628089,83628095,83628101,83628107,83628113,83628119,83628125,83628131,83628137,83628143,83628149,83628155,83628161,83628167,83628173,83628179,83628185,83628191,83628197,83628203,83628209,85567063,85567444,112950084,116008313,116008315,116008317,116008319,116008321,116008323,116008325,116008327,116008329,116008331,116008333,116008335,116008337,116008339,116008341,116008343,116008345,116008347,116008349,116090373,116090375,116090377,116090379,116090381,116090383,116710840,116710842,116710844,116710846,116710848,119593051,119593052,119593053,147744697,158259265,158260917,185178589,189053945,218421769,221040638,295007368,309323300,309323302,309323304,309323306,309323308,326415915,336169341,354334633,1004122737,1004122739,1198812681,1215172046,1215959750" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/P00451" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=2157" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000185010;t=ENST00000360256" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=F8" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=F8" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+2157" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/F8" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:2157" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/2157" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chrX&hgg_gene=ENST00000360256.9&hgg_start=154835792&hgg_end=155022723&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:3546" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:3546" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/f8" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=300841[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
|
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=300841[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/F8/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000185010" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=F8" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=F8" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=F8" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=F8&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA27952" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:3546" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:88383" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/F8#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:88383" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/2157/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA000437/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=2157" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-090629-2" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
|
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
|
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<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
|
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</span>
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</span>
|
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</div>
|
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:2157" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=F8&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
|
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
|
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<a id="number" class="mim-anchor"></a>
|
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 16872008, 26029002, 28293008<br />
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<strong>ICD10CM:</strong> D66<br />
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<strong>ICD9CM:</strong> 286.0<br />
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">ICD+</a>
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</div>
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<div>
|
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<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
300841
|
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</span>
|
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</span>
|
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</div>
|
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</div>
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<div>
|
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<a id="preferredTitle" class="mim-anchor"></a>
|
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<h3>
|
|
<span class="mim-font">
|
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|
|
COAGULATION FACTOR VIII; F8
|
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|
</span>
|
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</h3>
|
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</div>
|
|
<div>
|
|
<br />
|
|
</div>
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<div>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
|
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<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
FACTOR VIII<br />
|
|
COAGULATION FACTOR VIIIC, PROCOAGULANT COMPONENT; F8C
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
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</div>
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<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=F8" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">F8</a></em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/X/878?start=-3&limit=10&highlight=878">Xq28</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chrX:154835792-155022723&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">X:154,835,792-155,022,723</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=306700,301071" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/X/878?start=-3&limit=10&highlight=878">
|
|
Xq28
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Hemophilia A
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/306700"> 306700 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</abbr>
|
|
|
|
</span>
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<p>The F8 gene encodes coagulation factor VIII, a large plasma glycoprotein that functions in the blood coagulation cascade as a cofactor for the factor IXa (<a href="/entry/300746">300746</a>)-dependent activation of factor X (F10; <a href="/entry/613872">613872</a>). Factor VIII is activated proteolytically by a variety of coagulation enzymes, including thrombin (F2; <a href="/entry/176930">176930</a>). Factor VIII is tightly associated in the blood with von Willebrand factor (VWF; <a href="/entry/613160">613160</a>), which serves as a protective carrier protein for factor VIII (summary by <a href="#127" class="mim-tip-reference" title="Toole, J. J., Knopf, J. L., Wozney, J. M., Sultzman, L. A., Buecker, J. L., Pittman, D. D., Kaufman, R. J., Brown, E., Shoemaker, C., Orr, E. C., Amphlett, G. W., Foster, W. B., Coe, M. L., Knutson, G. J., Fass, D. N., Hewick, R. M. <strong>Molecular cloning of a cDNA encoding human antihaemophilic factor.</strong> Nature 312: 342-347, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438528</a>] [<a href="https://doi.org/10.1038/312342a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438528">Toole et al., 1984</a>; review by <a href="#60" class="mim-tip-reference" title="Hoyer, L. W. <strong>Hemophilia A.</strong> New Eng. J. Med. 330: 38-45, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8259143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8259143</a>] [<a href="https://doi.org/10.1056/NEJM199401063300108" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8259143">Hoyer, 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6438528+8259143" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#39" class="mim-tip-reference" title="Fay, P. J., Chavin, S. I., Schroeder, D., Young, F. E., Marder, V. J. <strong>Purification and characterization of a highly purified human factor VIII consisting of a single type of polypeptide chain.</strong> Proc. Nat. Acad. Sci. 79: 7200-7204, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6818542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6818542</a>] [<a href="https://doi.org/10.1073/pnas.79.23.7200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6818542">Fay et al. (1982)</a> isolated a highly purified human factor VIII that consisted of a single high molecular weight polypeptide chain having the highest specific activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6818542" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#127" class="mim-tip-reference" title="Toole, J. J., Knopf, J. L., Wozney, J. M., Sultzman, L. A., Buecker, J. L., Pittman, D. D., Kaufman, R. J., Brown, E., Shoemaker, C., Orr, E. C., Amphlett, G. W., Foster, W. B., Coe, M. L., Knutson, G. J., Fass, D. N., Hewick, R. M. <strong>Molecular cloning of a cDNA encoding human antihaemophilic factor.</strong> Nature 312: 342-347, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438528</a>] [<a href="https://doi.org/10.1038/312342a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438528">Toole et al. (1984)</a> isolated clones corresponding to the F8 gene from a human cDNA library. Independently and simultaneously, <a href="#44" class="mim-tip-reference" title="Gitschier, J., Wood, W. I., Goralka, T. M., Wion, K. L., Chen, E. Y., Eaton, D. H., Vehar, G. A., Capon, D. J., Lawn, R. M. <strong>Characterization of the human factor VIII gene.</strong> Nature 312: 326-330, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438525</a>] [<a href="https://doi.org/10.1038/312326a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438525">Gitschier et al. (1984)</a> and <a href="#136" class="mim-tip-reference" title="Wood, W. I., Capon, D. J., Simonsen, C. C., Eaton, D. L., Gitschier, J., Keyt, B., Seeburg, P. H., Smith, D. H., Hollingshead, P., Wion, K. L., Delwart, E., Tuddenham, E. G. D., Vehar, G. A., Lawn, R. M. <strong>Expression of active human factor VIII from recombinant DNA clones.</strong> Nature 312: 330-337, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438526</a>] [<a href="https://doi.org/10.1038/312330a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438526">Wood et al. (1984)</a> also cloned and expressed the F8 gene. The deduced precursor protein has 2,351 amino acids and a molecular mass of 267 kD. The leader sequence of the proprotein contains 19 amino acids, yielding a mature protein of 2,332 amino acids. The protein has an obvious domain structure, contains sequence repeats, and is structurally related to factor V (F5; <a href="/entry/612309">612309</a>) and ceruloplasmin (CP; <a href="/entry/117700">117700</a>). F8 has 3 copies of an A domain of 330 to 380 amino acids, a B domain of about 925 amino acids, and 2 C domains of about 160 amino acids. The domains are arranged A1-A2-B-A3-C1-C2. Both A and C repeats show conservation of cysteines, and the B region contains most potential N-glycosylation sites. Northern blot analysis detected a 9-kb F8 transcript. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6438525+6438526+6438528" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The F8 gene is expressed in human liver, spleen, lymph nodes, and a variety of other tissues, but not in bone marrow, peripheral blood lymphocytes, or endothelial cells (<a href="#135" class="mim-tip-reference" title="Wion, K. L., Kelly, D., Summerfield, J. A., Tuddenham, E. G., Lawn, R. M. <strong>Distribution of factor VIII mRNA and antigen in human liver and other tissues.</strong> Nature 317: 726-729, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3932885/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3932885</a>] [<a href="https://doi.org/10.1038/317726a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3932885">Wion et al., 1985</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3932885" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The F8 gene contains 26 exons and spans 186 kb (<a href="#44" class="mim-tip-reference" title="Gitschier, J., Wood, W. I., Goralka, T. M., Wion, K. L., Chen, E. Y., Eaton, D. H., Vehar, G. A., Capon, D. J., Lawn, R. M. <strong>Characterization of the human factor VIII gene.</strong> Nature 312: 326-330, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438525</a>] [<a href="https://doi.org/10.1038/312326a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438525">Gitschier et al., 1984</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6438525" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#77" class="mim-tip-reference" title="Levinson, B., Kenwrick, S., Lakich, D., Hammonds, G., Gitschier, J. <strong>A transcribed gene in an intron of the human factor VIII gene.</strong> Genomics 7: 1-11, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2110545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2110545</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90512-s" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2110545">Levinson et al. (1990)</a> found a curious example of a gene within a gene. In looking for transcripts from the Xq28 region, they found one referred to as the A gene that hybridized to a region in exon 22 of the F8 gene. The A or F8A gene (<a href="/entry/305423">305423</a>) was in reverse orientation to F8 and was contained entirely in intron 22. Computer analysis of the sequence suggested that the A gene encodes a protein, with the complication that codon usage analysis suggested a frameshift halfway through the gene. The A gene cDNA also bound to mouse, monkey, and rat genomic DNA in a 'zoo blot.' The mouse A gene was also found to be on the X chromosome but not within the mouse F8 gene as it is in the human. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2110545" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#41" class="mim-tip-reference" title="Freije, D., Schlessinger, D. <strong>A 1.6-Mb contig of yeast artificial chromosomes around the human factor VIII gene reveals three regions homologous to probes for the DXS115 locus and two for the DXYS64 locus.</strong> Am. J. Hum. Genet. 51: 66-80, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1609806/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1609806</a>]" pmid="1609806">Freije and Schlessinger (1992)</a> demonstrated that the X chromosome contains 3 copies of F8A and its adjacent regions, 1 in intron 22 and 2 telomeric and upstream to the F8 gene transcription start site. Gene F8A, which is transcribed in the opposite direction to F8, is intronless and completely nested within intron 22. Approximately 500 kb upstream of the F8 gene, there are 2 additional transcribed copies of the F8A gene. <a href="#73" class="mim-tip-reference" title="Lakich, D., Kazazian, H. H., Jr., Antonarakis, S. E., Gitschier, J. <strong>Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A.</strong> Nature Genet. 5: 236-241, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8275087/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8275087</a>] [<a href="https://doi.org/10.1038/ng1193-236" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8275087">Lakich et al. (1993)</a> pointed out that intron 22 is unusual in many respects. At 32 kb, it is the largest intron in the F8 gene. It also contains a CpG island, located about 10 kb downstream of exon 22. This island appears to serve as a bidirectional promoter for the F8A and F8B (<a href="/entry/305424">305424</a>) genes. The F8B gene is also located in intron 22 and is transcribed in the opposite direction from F8A; its first exon lies within intron 22 and is spliced to exons 23-26. The F8A and B genes are both expressed ubiquitously. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1609806+8275087" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Having previously reported the existence of 5 CpG islands close to the F8 gene, 4 of which they cloned by genomic walking, Gitschier's group (<a href="#70" class="mim-tip-reference" title="Kenwrick, S., Levinson, B., Taylor, S., Shapiro, A., Gitschier, J. <strong>Isolation and sequence of two genes associated with a CpG island 5-prime of the factor VIII gene.</strong> Hum. Molec. Genet. 1: 179-186, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1303175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1303175</a>] [<a href="https://doi.org/10.1093/hmg/1.3.179" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1303175">Kenwrick et al., 1992</a>) reported the isolation of the remaining island, located approximately 70 kb telomeric of the 5-prime end of the F8 gene. They identified cDNA clones corresponding to 2 transcribed sequences, C6.1A (BRCC3; <a href="/entry/300617">300617</a>) and C6.1B (MTCP1; <a href="/entry/300116">300116</a>), that originate from this CpG island. The C6.1A gene was highly conserved between species and expressed abundantly in many human and mouse tissues. No striking homologies to existing genes could be found for either sequence. <a href="#70" class="mim-tip-reference" title="Kenwrick, S., Levinson, B., Taylor, S., Shapiro, A., Gitschier, J. <strong>Isolation and sequence of two genes associated with a CpG island 5-prime of the factor VIII gene.</strong> Hum. Molec. Genet. 1: 179-186, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1303175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1303175</a>] [<a href="https://doi.org/10.1093/hmg/1.3.179" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1303175">Kenwrick et al. (1992)</a> found that both genes were deleted in 2 brothers who suffered from mental handicap and dysmorphism as well as hemophilia A (<a href="/entry/306700">306700</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1303175" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By in situ hybridization, <a href="#126" class="mim-tip-reference" title="Tantravahi, U., Murty, V. V. V. S., Jhanwar, S. C., Toole, J. J., Woozney, J. M., Chaganti, R. S. K., Latt, S. A. <strong>Physical mapping of the factor VIII gene proximal to two polymorphic DNA probes in human chromosome band Xq28: implications for factor VIII gene segregation analysis.</strong> Cytogenet. Cell Genet. 42: 75-79, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3013509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3013509</a>] [<a href="https://doi.org/10.1159/000132255" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3013509">Tantravahi et al. (1986)</a> concluded that the F8 gene is located in the proximal part of chromosome Xq28 with probes DX13 and St14 distally located. Using a hybrid cell line that contains only a terminal Xq28 fragment, <a href="#126" class="mim-tip-reference" title="Tantravahi, U., Murty, V. V. V. S., Jhanwar, S. C., Toole, J. J., Woozney, J. M., Chaganti, R. S. K., Latt, S. A. <strong>Physical mapping of the factor VIII gene proximal to two polymorphic DNA probes in human chromosome band Xq28: implications for factor VIII gene segregation analysis.</strong> Cytogenet. Cell Genet. 42: 75-79, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3013509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3013509</a>] [<a href="https://doi.org/10.1159/000132255" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3013509">Tantravahi et al. (1986)</a> found that F8 probes did not hybridize but the DX13 and St14 did hybridize to the DNA of that cell line. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3013509" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#104" class="mim-tip-reference" title="Patterson, M., Schwartz, C., Bell, M., Sauer, S., Hofker, M., Trask, B., van den Engh, G., Davies, K. E. <strong>Physical mapping studies on the human X chromosome in the region Xq27-Xqter.</strong> Genomics 1: 297-306, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3482420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3482420</a>] [<a href="https://doi.org/10.1016/0888-7543(87)90028-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3482420">Patterson et al. (1987)</a> showed that the G6PD (<a href="/entry/305900">305900</a>) and F8 genes lie within 500 kb of each other. <a href="#12" class="mim-tip-reference" title="Arveiler, B., Vincent, A., Mandel, J.-L. <strong>Toward a physical map of the Xq28 region in man: linking color vision, G6PD, and coagulation factor VIII genes to an X-Y homology region.</strong> Genomics 4: 460-471, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2501212/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2501212</a>] [<a href="https://doi.org/10.1016/0888-7543(89)90269-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2501212">Arveiler et al. (1989)</a> showed that G6PD and F8 are in the same 290-kb pulsed field gel electrophoresis fragment, but did not establish which of the genes is more proximal. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3482420+2501212" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#69" class="mim-tip-reference" title="Kenwrick, S., Gitschier, J. <strong>A contiguous, 3-Mb physical map of Xq28 extending from the colorblindness locus to DXS15.</strong> Am. J. Hum. Genet. 45: 873-882, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2589319/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2589319</a>]" pmid="2589319">Kenwrick and Gitschier (1989)</a> established the order: cen--R/GCP--GDX--G6PD--F8--DXS15--tel. The direction of transcription of the GDX, G6PD, and F8 genes is toward the centromere, i.e., the R/GCP end of the region. <a href="#103" class="mim-tip-reference" title="Patterson, M., Gitschier, J., Bloomfield, J., Bell, M., Dorkins, H., Froster-Iskenius, U., Sommer, S., Sobell, J., Schaid, D., Thibodeau, S., Davies, K. E. <strong>An intronic region within the human factor VIII gene is duplicated within Xq28 and is homologous to the polymorphic locus DXS115 (767).</strong> Am. J. Hum. Genet. 44: 679-685, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2565080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2565080</a>]" pmid="2565080">Patterson et al. (1989)</a> showed that the genomic sequences recognized by the anonymous probe 767 (DXS115) are localized to 2 sites within Xq28. One site lies within intron 22 of the F8 gene. The second site, which contains the RFLPs detected by 767, is located within 1.2 megabases of the F8 gene. Genetic data indicate tight linkage of F8 and DXS115; maximum lod = 8.30 at theta = 0.04. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2589319+2565080" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>G6PD (<a href="/entry/305900">305900</a>) is one of the 5 rather tightly linked loci located on Xq28, the others being CBD (<a href="/entry/303800">303800</a>), CBP (<a href="/entry/303900">303900</a>), HEMA, and ALD (<a href="/entry/300371">300371</a>). In a physical map of the most distal 12 Mb of Xq, <a href="#109" class="mim-tip-reference" title="Poustka, A., Dietrich, A., Langenstein, G., Toniolo, D., Warren, S. T., Lehrach, H. <strong>Physical map of human Xq27-qter: localizing the region of the fragile X mutation.</strong> Proc. Nat. Acad. Sci. 88: 8302-8306, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1924290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1924290</a>] [<a href="https://doi.org/10.1073/pnas.88.19.8302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1924290">Poustka et al. (1991)</a> found that the F8 gene lies about 1.1 Mb from the telomere, with G6PD proximal to it, and about 1.5 Mb from the telomere. This contradicted the earlier impression that the gene is located in the proximal part of Xq28. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1924290" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 9-year-old Malaysian female with de novo hemophilia A (<a href="/entry/306700">306700</a>) as well as a complex de novo translocation involving one X chromosome and one chromosome 17 (<a href="#89" class="mim-tip-reference" title="Muneer, R. S., Coffman, M. A., Thompson, L. M., Sexauer, C. L., Rennert, O. M. <strong>Classic hemophilia in a female with X/17 complex translocation and partial deletion of the long arm X chromosome (Xq11-13). (Abstract)</strong> Am. J. Hum. Genet. 39: A126, 1986."None>Muneer et al., 1986</a>), <a href="#85" class="mim-tip-reference" title="Migeon, B. R., McGinniss, M. J., Antonarakis, S. E., Axelman, J., Stasiowski, B. A., Youssoufian, H., Kearns, W. G., Chung, A., Pearson, P. L., Kazazian, H. H., Jr., Muneer, R. S. <strong>Severe hemophilia A in a female by cryptic translocation: order and orientation of factor VIII within Xq28.</strong> Genomics 16: 20-25, 1993. Note: Erratum: Genomics 16: 792 only, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8486358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8486358</a>] [<a href="https://doi.org/10.1006/geno.1993.1134" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8486358">Migeon et al. (1993)</a> identified a breakpoint within Xq28 with deletion of the 5-prime end of the factor VIII gene, leaving the more proximal G6PD locus intact on the derivative chromosome 17. As the deleted segment included the 5-prime half of F8C as well as the subtelomeric DXYS64 locus, they concluded that F8 is oriented on the chromosome with its 5-prime region closest to the telomere. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8486358" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Factor VII is a complex of a large inert carrier protein (VWF; <a href="/entry/613160">613160</a>) and a noncovalently bound small fragment which contains the procoagulant active site. <a href="#146" class="mim-tip-reference" title="Zacharski, L. R., Bowie, E. J. W., Titus, J. L., Owen, C. A., Jr. <strong>Synthesis of antihemophilic factor (factor VIII) by leukocytes: preliminary report.</strong> Mayo Clin. Proc. 43: 617-619, 1968.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5751674/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5751674</a>]" pmid="5751674">Zacharski et al. (1968)</a> showed that leukocytes synthesize some factor VIII in vitro; however, it is synthesized primarily in the liver. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5751674" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#30" class="mim-tip-reference" title="Cooper, H. A., Wagner, R. H. <strong>The defect in hemophilic and von Willebrand's disease. Plasmas studied by a recombination technique.</strong> J. Clin. Invest. 54: 1093-1099, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4213756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4213756</a>] [<a href="https://doi.org/10.1172/JCI107853" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4213756">Cooper and Wagner (1974)</a> presented evidence that the carrier molecule is normally present in the plasma of hemophilia A patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4213756" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#39" class="mim-tip-reference" title="Fay, P. J., Chavin, S. I., Schroeder, D., Young, F. E., Marder, V. J. <strong>Purification and characterization of a highly purified human factor VIII consisting of a single type of polypeptide chain.</strong> Proc. Nat. Acad. Sci. 79: 7200-7204, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6818542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6818542</a>] [<a href="https://doi.org/10.1073/pnas.79.23.7200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6818542">Fay et al. (1982)</a> isolated a highly purified human factor VIII that consisted of a single high molecular weight polypeptide chain having the highest specific activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6818542" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#111" class="mim-tip-reference" title="Ratnoff, O. D., Bennett, B. <strong>The genetics of hereditary disorders of blood coagulation.</strong> Science 179: 1291-1298, 1973.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4568863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4568863</a>] [<a href="https://doi.org/10.1126/science.179.4080.1291" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4568863">Ratnoff and Bennett (1973)</a> reviewed the genetics of hereditary disorders of blood coagulation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4568863" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Hemophilia A</em></strong></p><p>
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<a href="#46" class="mim-tip-reference" title="Gitschier, J., Wood, W. I., Tuddenham, E. G. D., Shuman, M. A., Goralka, T. M., Chen, E. Y., Lawn, R. M. <strong>Detection and sequence of mutations in the factor VIII gene of haemophiliacs.</strong> Nature 315: 427-430, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2987704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2987704</a>] [<a href="https://doi.org/10.1038/315427a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2987704">Gitschier et al. (1985)</a> identified truncating mutations in the F8 gene (see, e.g., <a href="#0001">300841.0001</a>-<a href="#0003">300841.0003</a>) as the basis for hemophilia A (<a href="/entry/306700">306700</a>). A severe hemophiliac with no detectable factor VIIIC activity had an R2307X mutation (<a href="#0001">300841.0001</a>). <a href="#45" class="mim-tip-reference" title="Gitschier, J., Wood, W. I., Shuman, M. A., Lawn, R. M. <strong>Identification of a missense mutation in the factor VIII gene of a mild hemophiliac.</strong> Science 232: 1415-1416, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3012775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3012775</a>] [<a href="https://doi.org/10.1126/science.3012775" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3012775">Gitschier et al. (1986)</a> found that the same codon was converted to glutamine (R2307Q; <a href="#0042">300841.0042</a>) in a mild hemophiliac with 10% of normal activity. A diminished level of factor VIII Ag in the latter patient coincided with the level of clotting activity, suggesting that the abnormal factor VIII was relatively unstable. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2987704+3012775" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a study of 83 patients with hemophilia A, <a href="#144" class="mim-tip-reference" title="Youssoufian, H., Kazazian, H. H., Jr., Phillips, D. G., Aronis, S., Tsiftis, G., Brown, V. A., Antonarakis, S. E. <strong>Recurrent mutations in haemophilia A give evidence for CpG mutation hotspots.</strong> Nature 324: 380-382, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3097553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3097553</a>] [<a href="https://doi.org/10.1038/324380a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3097553">Youssoufian et al. (1986)</a> identified 2 different point mutations, one in exon 18 and one in exon 22, that recurred independently in unrelated families. Each mutation produced a nonsense codon by a change of CG to TG. In the opinion of <a href="#144" class="mim-tip-reference" title="Youssoufian, H., Kazazian, H. H., Jr., Phillips, D. G., Aronis, S., Tsiftis, G., Brown, V. A., Antonarakis, S. E. <strong>Recurrent mutations in haemophilia A give evidence for CpG mutation hotspots.</strong> Nature 324: 380-382, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3097553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3097553</a>] [<a href="https://doi.org/10.1038/324380a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3097553">Youssoufian et al. (1986)</a>, these observations indicated that CpG dinucleotides are mutation hotspots. It had been postulated that methylated cytosines may be mutation hotspots because 5-methylcytosine can spontaneously deaminate to thymine, resulting in a C-to-T transition in DNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3097553" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#76" class="mim-tip-reference" title="Levinson, B., Janco, R., Phillips, J., III, Gitschier, J. <strong>A novel missense mutation in the factor VIII gene identified by analysis of amplified hemophilia DNA sequences.</strong> Nucleic Acids Res. 15: 9797-9805, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3122181/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3122181</a>] [<a href="https://doi.org/10.1093/nar/15.23.9797" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3122181">Levinson et al. (1987)</a> used RNAse A cleavage and DNA sequencing of the altered region to identify a mutation in the F8 gene in a patient with hemophilia. The mutation was a novel G-to-C transversion which resulted in a missense mutation, with proline being substituted for arginine in one of the active domains of the factor VIII molecule. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3122181" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#140" class="mim-tip-reference" title="Youssoufian, H., Antonarakis, S. E., Aronis, S., Tsiftis, G., Phillips, D. G., Kazazian, H. H., Jr. <strong>Characterization of five partial deletions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 84: 3772-3776, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3035554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3035554</a>] [<a href="https://doi.org/10.1073/pnas.84.11.3772" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3035554">Youssoufian et al. (1987)</a> characterized 5 different partial deletions of the F8 gene in 83 patients with hemophilia. None had developed circulating inhibitors. One of the deletions occurred de novo in a germ cell of the maternal grandmother, while a second deletion occurred in a germ cell of a maternal grandfather. The findings indicated that de novo deletions of X-linked genes can occur in either male or female gametes. <a href="#141" class="mim-tip-reference" title="Youssoufian, H., Antonarakis, S. E., Bell, W., Griffin, A. M., Kazazian, H. H., Jr. <strong>Nonsense and missense mutations in hemophilia A: estimate of the relative mutation rate at CG dinucleotides.</strong> Am. J. Hum. Genet. 42: 718-725, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2833855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2833855</a>]" pmid="2833855">Youssoufian et al. (1988)</a> reported 6 other partial F8 gene deletions in severe hemophilia A, bringing to 12 the number of deletions among 240 patients. No association was observed between the size or location of deletions and the presence of inhibitors to factor VIII. Furthermore, no 'hotspots' for deletion breakpoints were identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2833855+3035554" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#141" class="mim-tip-reference" title="Youssoufian, H., Antonarakis, S. E., Bell, W., Griffin, A. M., Kazazian, H. H., Jr. <strong>Nonsense and missense mutations in hemophilia A: estimate of the relative mutation rate at CG dinucleotides.</strong> Am. J. Hum. Genet. 42: 718-725, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2833855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2833855</a>]" pmid="2833855">Youssoufian et al. (1988)</a> screened 240 patients with hemophilia A and found CG to TG transitions in an exon in 9. They identified novel missense mutations leading to severe hemophilia A and estimated that the extent of hypermutability of CpG dinucleotides is 10 to 20 times greater than the average mutation rate for hemophilia A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2833855" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#29" class="mim-tip-reference" title="Cooper, D. N., Youssoufian, H. <strong>The CpG dinucleotide and human genetic disease.</strong> Hum. Genet. 78: 151-155, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3338800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3338800</a>] [<a href="https://doi.org/10.1007/BF00278187" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3338800">Cooper and Youssoufian (1988)</a> collated reports of single basepair mutations within gene coding regions causing human genetic disease. They found that 35% of mutations occurred within CpG dinucleotides. Over 90% of these mutations were C-to-T or G-to-A transitions, which thus occur within coding regions at a frequency 42-times higher than that predicted from random mutation. <a href="#29" class="mim-tip-reference" title="Cooper, D. N., Youssoufian, H. <strong>The CpG dinucleotide and human genetic disease.</strong> Hum. Genet. 78: 151-155, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3338800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3338800</a>] [<a href="https://doi.org/10.1007/BF00278187" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3338800">Cooper and Youssoufian (1988)</a> believed these findings were consistent with methylation-induced deamination of 5-methylcytosine and suggested that methylation of DNA within coding regions may contribute significantly to the incidence of human genetic disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3338800" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#56" class="mim-tip-reference" title="Higuchi, M., Kochhan, L., Olek, K. <strong>A somatic mosaic for haemophilia A detected at the DNA level.</strong> Molec. Biol. Med. 5: 23-27, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3131627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3131627</a>]" pmid="3131627">Higuchi et al. (1988)</a> found deletion of about 2,000 bases spanning exon 3 and part of IVS3 of the F8 gene in a patient with severe hemophilia A. The mother was judged to be a somatic mosaic because the defective gene could be identified in only a portion of the leukocytes and cultured fibroblasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3131627" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By use of a cDNA probe corresponding to exons 14-26 of F8, <a href="#13" class="mim-tip-reference" title="Bardoni, B., Sampietro, M., Romano, M., Crapanzano, M., Mannucci, P. M., Camerino, G. <strong>Characterization of a partial deletion of the factor VIII gene in a haemophiliac with inhibitor.</strong> Hum. Genet. 79: 86-88, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2835307/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2835307</a>] [<a href="https://doi.org/10.1007/BF00291718" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2835307">Bardoni et al. (1988)</a> studied 49 Italian patients with severe hemophilia A. They found no TaqI site mutations, but did find a partial deletion, eliminating exons 15-18 and spanning about 13 kb (<a href="#0046">300841.0046</a>), in a patient with anti-factor VIII antibodies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2835307" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a case of hemophilia A, <a href="#68" class="mim-tip-reference" title="Kazazian, H. H., Jr., Wong, C., Youssoufian, H., Scott, A. F., Phillips, D. G., Antonarakis, S. E. <strong>Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in man.</strong> Nature 332: 164-166, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2831458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2831458</a>] [<a href="https://doi.org/10.1038/332164a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2831458">Kazazian et al. (1988)</a> described the first instance of insertional mutagenesis in man caused by a long inserted element (LINE) in the F8 gene. L1 (LINE-1) sequences are a human-specific family of long, interspersed, repetitive elements, present in about 100,000 copies dispersed throughout the genome. The full-length L1 sequence is 6.1 kilobases, but most L1 elements are truncated at the 5-prime end, resulting in a 5-fold higher copy number of 3-prime sequences. <a href="#68" class="mim-tip-reference" title="Kazazian, H. H., Jr., Wong, C., Youssoufian, H., Scott, A. F., Phillips, D. G., Antonarakis, S. E. <strong>Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in man.</strong> Nature 332: 164-166, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2831458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2831458</a>] [<a href="https://doi.org/10.1038/332164a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2831458">Kazazian et al. (1988)</a> found insertions of L1 elements into exon 14 of the F8 gene in 2 of 240 unrelated patients with hemophilia A. Both of these insertions (3.8 and 2.3 kb, respectively) contained 3-prime portions of the L1 sequence. They interpreted these results as indicating that certain L1 sequences in man can be dispersed, presumably by an RNA intermediate, and cause disease by insertional mutation. Both of the above insertions were de novo events, appearing either during embryogenesis in the patient or in the mother's germ cells. The L1 element transposed into one of these patients was demonstrated by <a href="#35" class="mim-tip-reference" title="Dombroski, B. A., Mathias, S. L., Nanthakumar, E., Scott, A. F., Kazazian, H. H., Jr. <strong>Isolation of an active human transposable element.</strong> Science 254: 1805-1808, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1662412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1662412</a>] [<a href="https://doi.org/10.1126/science.1662412" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1662412">Dombroski et al. (1991)</a> to have come from a retrotransposable element located on chromosome 22 (see <a href="/entry/151626">151626</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2831458+1662412" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#137" class="mim-tip-reference" title="Woods-Samuels, P., Wong, C., Mathias, S. L., Scott, A. F., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>Characterization of a nondeleterious L1 insertion in an intron of the human factor VIII gene and further evidence of open reading frames in functional L1 elements.</strong> Genomics 4: 290-296, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2497061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2497061</a>] [<a href="https://doi.org/10.1016/0888-7543(89)90332-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2497061">Woods-Samuels et al. (1989)</a> characterized a third L1 insertion in intron 10 of the F8 gene of a hemophilia A patient. This L1 insertion was not a cause of hemophilia in the patient because it was also present in the maternal grandfather, who did not have the disease. Altogether the L1 insertion was present in 4 generations of the family. All 3 of the L1 insertions discovered by <a href="#35" class="mim-tip-reference" title="Dombroski, B. A., Mathias, S. L., Nanthakumar, E., Scott, A. F., Kazazian, H. H., Jr. <strong>Isolation of an active human transposable element.</strong> Science 254: 1805-1808, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1662412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1662412</a>] [<a href="https://doi.org/10.1126/science.1662412" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1662412">Dombroski et al. (1991)</a> have open reading frames (ORFs), and the 3 derived amino acid sequences are 98 to 99% identical. They show similarity in the sequence of the L1 3-prime ORFs, and the polymerase domain of reverse transcriptase was observed in all 3 L1 insertions. The presence of ORFs and the close sequence similarity of these recently inserted L1 elements provide indirect evidence for the existence of a set of functional L1 elements that encodes 1 or more proteins necessary for their retrotransposition. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2497061+1662412" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In studies of 83 unrelated Finnish patients with hemophilia A, <a href="#77" class="mim-tip-reference" title="Levinson, B., Kenwrick, S., Lakich, D., Hammonds, G., Gitschier, J. <strong>A transcribed gene in an intron of the human factor VIII gene.</strong> Genomics 7: 1-11, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2110545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2110545</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90512-s" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2110545">Levinson et al. (1990)</a> identified specific mutations, falling into 3 classes, in 10 patients: 5 mutations caused loss of TaqI restriction sites; 1 point mutation resulted in a new TaqI site; and 4 represented partial gene deletions. Although exons 5 and 6 were involved in 3 of the 4 partial gene deletions, the extent of the DNA loss differed in each. The fourth deletion was located entirely within intron 1. There was no history of hemophilia in 8 of the 10 families. The origin of the mutation was determined in 6 of these pedigrees, 2 of which showed evidence for maternal mosaicism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2110545" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#25" class="mim-tip-reference" title="Brocker-Vriends, A. H. J. T., Briet, E., Dreesen, J. C. F. M., Bakker, B., Reitsma, P., Pannekoek, H., van de Kamp, J. J. P., Pearson, P. L. <strong>Somatic origin of inherited haemophilia A.</strong> Hum. Genet. 85: 288-292, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1975557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1975557</a>] [<a href="https://doi.org/10.1007/BF00206748" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1975557">Brocker-Vriends et al. (1990)</a> described a case of hemophilia A due to partial deletion of the F8 gene of about 2 kb, spanning exon 5 and part of introns 4 and 5; the mother was a somatic and presumably gonadal mosaic for the mutation although coagulation assays and RFLP analysis in the family did not suggest a carrier status. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1975557" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#84" class="mim-tip-reference" title="McGinniss, M. J., Kazazian, H. H., Jr., Hoyer, L. W., Bi, L., Inaba, H., Antonarakis, S. E. <strong>Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A.</strong> Genomics 15: 392-398, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8449505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8449505</a>] [<a href="https://doi.org/10.1006/geno.1993.1073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8449505">McGinniss et al. (1993)</a> reported that half of hemophilia A patients have no detectable factor VIII; about 5% have normal levels of dysfunctional factor VIII as protein and are termed CRM-+, whereas the rest ( 45%) have plasma factor VIII Ag protein reduced to an extent roughly comparable to the level of factor VIIIC activity and are designated CRM-reduced. They found in an analysis of mutations that almost all CRM-positive/reduced mutations (24/26) were missense, and many (12/26) occurred at CpG dinucleotides. They showed that 18 of 19 amino acid residues altered by mutation in these patients were conserved in the porcine and murine sequences. Almost half of the mutations (11/26) were clustered in the A2 domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8449505" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a review, <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> collected the findings of more than 1,000 hemophilia subjects examined for F8 gene mutations. These include point mutations, inversions, deletions, and unidentified mutations which constitute 46%, 42%, 8%, 4%, and 91%, 0%, 0%, and 9%, respectively, of those with severe versus mild to moderate disease, respectively, in selected studies. The 266 point mutations described as of April, 1994 comprised missense (53%), CpG-to-TpG (16%), small deletions (12%), nonsense (9%), small inversions and splicing (3% each), and missense polymorphisms and silent mutations in exons (2% each). In addition to these point mutations 100 different larger deletions and 9 insertion mutations had been reported. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a study of 147 sporadic cases of severe hemophilia A, <a href="#16" class="mim-tip-reference" title="Becker, J., Schwaab, R., Moller-Taube, A., Schwaab, U., Schmidt, W., Brackmann, H. H., Grimm, T., Olek, K., Oldenburg, J. <strong>Characterization of the factor VIII defect in 147 patients with sporadic hemophilia A: family studies indicate a mutation type-dependent sex ratio of mutation frequencies.</strong> Am. J. Hum. Genet. 58: 657-670, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8644728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8644728</a>]" pmid="8644728">Becker et al. (1996)</a> were able to identify the causative defect in the F8 gene in 126 patients (85.7%). An inversion of the gene was found in 55 patients (37.4%), a point mutation in 47 (32%), a small deletion in 14 (9.5%), a large deletion in 8 (5.4%), and a small insertion in 2 (1.4%). In 4 (2.7%), mutations were localized but not yet sequenced. No mutation was identified in 17 patients (11.6%). The identified mutations occurred in the B domain in 16 (10.9%); 4 of these were located in an adenosine nucleotide stretch at codon 1192, indicating a mutation hotspot. Somatic mosaicism was detected in 3 (3.9%) of 76 patients' mothers, comprising 3 of 16 de novo mutations in the patients' mothers. Investigation of family relatives allowed detection of a de novo mutation in 16 of 76 2-generation and 28 of 34 3-generation families. On the basis of these data, <a href="#16" class="mim-tip-reference" title="Becker, J., Schwaab, R., Moller-Taube, A., Schwaab, U., Schmidt, W., Brackmann, H. H., Grimm, T., Olek, K., Oldenburg, J. <strong>Characterization of the factor VIII defect in 147 patients with sporadic hemophilia A: family studies indicate a mutation type-dependent sex ratio of mutation frequencies.</strong> Am. J. Hum. Genet. 58: 657-670, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8644728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8644728</a>]" pmid="8644728">Becker et al. (1996)</a> estimated the male:female ratio of mutation frequencies (k) to be 3.6. By use of the quotients of mutation origin in maternal grandfather to patients' mother or to maternal grandmother, k values were directly estimated as 15 and 7.5, respectively. Considering each mutation type separately, they found a mutation type-specific sex ratio of mutation frequencies. Point mutations showed a 5-to-10-fold-higher and inversions a more than 10-fold-higher mutation rate in male germ cells, whereas deletions showed a more than 5-fold-higher mutation rate in female germ cells. Consequently, and in accordance with the data of other disorders such as Duchenne muscular dystrophy, the results indicated to <a href="#16" class="mim-tip-reference" title="Becker, J., Schwaab, R., Moller-Taube, A., Schwaab, U., Schmidt, W., Brackmann, H. H., Grimm, T., Olek, K., Oldenburg, J. <strong>Characterization of the factor VIII defect in 147 patients with sporadic hemophilia A: family studies indicate a mutation type-dependent sex ratio of mutation frequencies.</strong> Am. J. Hum. Genet. 58: 657-670, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8644728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8644728</a>]" pmid="8644728">Becker et al. (1996)</a> that at least for X-chromosomal disorders the male:female mutation rate is determined by its proportion of the different mutation types. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8644728" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The molecular diagnosis of hemophilia A is challenging because of the high number of different causative mutations that are distributed through the large F8 gene. The putative role of the novel mutations, especially missense mutations, may be difficult to interpret as causing hemophilia A. <a href="#53" class="mim-tip-reference" title="Guillet, B., Lambert, T., d'Oiron, R., Proulle, V., Plantier, J.-L., Rafowicz, A., Peynet, J., Costa, J.-M., Bendelac, L., Laurian, Y., Lavergne, J.-M. <strong>Detection of 95 novel mutations in coagulation factor VIII gene F8 responsible for hemophilia A: results from a single institution.</strong> Hum. Mutat. 27: 676-685, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16786531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16786531</a>] [<a href="https://doi.org/10.1002/humu.20345" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16786531">Guillet et al. (2006)</a> identified 95 novel mutations out of 180 different mutations found among 515 patients with hemophilia A from 406 unrelated families followed up at a single hemophilia treatment center in a Paris hospital. The 95 novel mutations comprised 55 missense mutations, 12 nonsense mutations, 11 splice site mutations, and 17 small insertions/deletions. They used a strategy in interpreting the causality of novel F8 mutations based on a combination of the familial segregation of the mutation, the resulting biologic and clinical hemophilia A phenotype, and the molecular consequences of the amino acid substitution. For the latter, they studied the putative biochemical modifications: its conservation status with cross-species factor VIII and homologous proteins, its putative location in known factor VIII functional regions, and its spatial position in the available factor VIII 3D structures. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16786531" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Among 1,410 Italian patients with hemophilia A, <a href="#118" class="mim-tip-reference" title="Santacroce, R., Acquila, M., Belvini, D., Castaldo, G., Garagiola, I., Giacomelli, S. H., Lombardi, A. M., Minuti, B., Riccardi, F., Salviato, R., Tagliabue, L., Grandone, E., Margaglione, M., the AICE-Genetics Study Group. <strong>Identification of 217 unreported mutations in the F8 gene in a group of 1,410 unselected Italian patients with hemophilia A.</strong> J. Hum. Genet. 53: 275-284, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18217193/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18217193</a>] [<a href="https://doi.org/10.1007/s10038-007-0238-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18217193">Santacroce et al. (2008)</a> identified 382 different mutations in the F8 gene, 217 (57%) of which had not previously been reported. Mutations leading to a null allele accounted for 82%, 15%, and less than 1% of severe, moderate, or mild hemophilia, respectively. Missense mutations were identified in 16%, 68%, and 81% of severe, moderate, or mild hemophilia, respectively, yielding a good genotype/phenotype correlation useful for treatment and genetic counseling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18217193" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To establish a national database of F8 mutations, <a href="#50" class="mim-tip-reference" title="Green, P. M., Bagnall, R. D., Waseem, N. H., Giannelli, F. <strong>Haemophilia A mutations in the UK: results of screening one-third of the population.</strong> Brit. J. Haemat. 143: 115-128, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18691168/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18691168</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2008.07310.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18691168">Green et al. (2008)</a> identified and cataloged multiple mutations in approximately one-third of the U.K. hemophilia A population. The risk of developing inhibitors for patients with nonsense mutations was greater when the stop codon was in the 3-prime half of the mRNA. The most common change was the intron 22 inversion (<a href="#0067">300841.0067</a>), which accounted for 16.6% of all mutations and for 38% of those causing severe disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18691168" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Inversion Mutations in Intron 22 of the F8 Gene</em></strong></p><p>
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Intron 22 of the human F8 gene is hypomethylated on the active X and methylated on the inactive X. <a href="#62" class="mim-tip-reference" title="Inaba, H., Fujimaki, M., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>MspI polymorphic site in intron 22 of the factor VIII gene in the Japanese population.</strong> Hum. Genet. 84: 214-215, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1688823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1688823</a>] [<a href="https://doi.org/10.1007/BF00208947" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1688823">Inaba et al. (1990)</a> described an MspI RFLP in intron 22 of the F8 gene. Japanese showed 45% heterozygosity and Asian Indians showed 13%; polymorphism was not found in American blacks or Caucasians. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1688823" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#96" class="mim-tip-reference" title="Naylor, J. A., Green, P. M., Rizza, C. R., Giannelli, F. <strong>Factor VIII gene explains all cases of haemophilia A.</strong> Lancet 340: 1066-1067, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1357455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1357455</a>] [<a href="https://doi.org/10.1016/0140-6736(92)93080-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1357455">Naylor et al. (1992)</a> found an unusual cluster of mutations involving regions of intron 22 not examined earlier and leading to defective joining of exons 22 and 23 in the mRNA (<a href="#0067">300841.0067</a>) as the cause of hemophilia A in 10 of 24 severely affected UK patients. These results confirmed predictions about the efficacy of the mRNA-based method suggested by <a href="#95" class="mim-tip-reference" title="Naylor, J. A., Green, P. M., Montandon, A. J., Rizza, C. R., Giannelli, F. <strong>Detection of three novel mutations in two haemophilia A patients by rapid screening of whole essential region of factor VIII gene.</strong> Lancet 337: 635-639, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1671991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1671991</a>] [<a href="https://doi.org/10.1016/0140-6736(91)92450-g" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1671991">Naylor et al. (1991)</a>, and also excluded hypotheses proposing that mutations outside the F8 gene are responsible for a large proportion of severe hemophilia A. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1671991+1357455" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Of the 28 patients reported by <a href="#97" class="mim-tip-reference" title="Naylor, J. A., Green, P. M., Rizza, C. R., Giannelli, F. <strong>Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients.</strong> Hum. Molec. Genet. 2: 11-17, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490618</a>] [<a href="https://doi.org/10.1093/hmg/2.1.11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490618">Naylor et al. (1993)</a>, 5 had mild or moderate disease and all had a missense mutation. The other 23 patients were severely affected; unexpectedly, intron 22 seemed to be the target of approximately 40% of the mutations causing severe hemophilia A. <a href="#97" class="mim-tip-reference" title="Naylor, J. A., Green, P. M., Rizza, C. R., Giannelli, F. <strong>Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients.</strong> Hum. Molec. Genet. 2: 11-17, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490618</a>] [<a href="https://doi.org/10.1093/hmg/2.1.11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490618">Naylor et al. (1993)</a> found that the basis of the unique F8 mRNA defect that prevented PCR amplification across the boundary between exons 22 and 23 was an abnormality in the internal regions of intron 22. They showed that exons 1-22 of the F8 mRNA had become part of a hybrid message containing new multiexonic sequences expressed in normal cells. The novel sequences were not located in a YAC containing the whole F8 gene. Southern blots from patients probed by novel sequences and clones covering intron 22 showed no obvious abnormalities. <a href="#97" class="mim-tip-reference" title="Naylor, J. A., Green, P. M., Rizza, C. R., Giannelli, F. <strong>Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients.</strong> Hum. Molec. Genet. 2: 11-17, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490618</a>] [<a href="https://doi.org/10.1093/hmg/2.1.11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490618">Naylor et al. (1993)</a> also suggested that inversions involving intron 22 repeated sequences are the basis of the mRNA defect. These mutations in severely affected patients occur at the surprising rate of approximately 4 x 10(-6) per gene per gamete per generation. Furthermore, it has been shown that these de novo inversions occur more frequently in males than females with a ratio of 302:1 estimated in male:female germ cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8490618" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The F8A gene (<a href="/entry/305423">305423</a>) is contained entirely within intron 22 of the F8 gene and is transcript in the reverse orientation from the F8 gene (<a href="#77" class="mim-tip-reference" title="Levinson, B., Kenwrick, S., Lakich, D., Hammonds, G., Gitschier, J. <strong>A transcribed gene in an intron of the human factor VIII gene.</strong> Genomics 7: 1-11, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2110545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2110545</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90512-s" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2110545">Levinson et al., 1990</a>). <a href="#73" class="mim-tip-reference" title="Lakich, D., Kazazian, H. H., Jr., Antonarakis, S. E., Gitschier, J. <strong>Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A.</strong> Nature Genet. 5: 236-241, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8275087/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8275087</a>] [<a href="https://doi.org/10.1038/ng1193-236" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8275087">Lakich et al. (1993)</a> proposed that many of the previously unidentified mutations resulting in severe hemophilia A are based on recombination between the homologous F8A sequences within intron 22 and upstream of the F8 gene. Such a recombination would lead to an inversion of all intervening DNA and a disruption of the gene. <a href="#73" class="mim-tip-reference" title="Lakich, D., Kazazian, H. H., Jr., Antonarakis, S. E., Gitschier, J. <strong>Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A.</strong> Nature Genet. 5: 236-241, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8275087/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8275087</a>] [<a href="https://doi.org/10.1038/ng1193-236" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8275087">Lakich et al. (1993)</a> presented evidence to support this model and described a Southern blot assay that detects the inversion. They suggested that this assay should permit genetic prediction of hemophilia A in approximately 45% of families with severe disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2110545+8275087" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#116" class="mim-tip-reference" title="Rossiter, J. P., Young, M., Kimberland, M. L., Hutter, P., Ketterling, R. P., Gitschier, J., Horst, J., Morris, M. A., Schaid, D. J., de Moerloose, P., Sommer, S. S., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>Factor VIII gene inversions causing severe hemophilia A originate almost exclusively in male germ cells.</strong> Hum. Molec. Genet. 3: 1035-1039, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7981669/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7981669</a>] [<a href="https://doi.org/10.1093/hmg/3.7.1035" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7981669">Rossiter et al. (1994)</a> hypothesized that pairing of Xq with its homolog inhibits the intrachromosomal inversion that is responsible for nearly half of all cases of severe hemophilia A. This would predict that the event originates predominantly in male germ cells. They presented findings supporting the hypothesis: in all 20 informative cases in which the inversion originated in a maternal grandparent, DNA polymorphism analysis determined that it occurred in the male germline. In addition, all but 1 of 50 mothers of sporadic cases due to an inversion were carriers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7981669" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Inversion mutations resulting from recombinations between DNA sequences in the A gene in intron 22 of the F8 gene and 1 of 2 other A genes upstream to F8 have been shown to cause a large portion of cases. From data on more than 2,000 samples, <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> concluded that the common inversion mutations are found in 42% of all severe hemophilia A subjects. Whereas 98% of the mothers of those with inversions were carriers of the inversion, only about 1 de novo inversion was found in maternal cells for every 25 mothers of sporadic cases. When the maternal grandparental origin of inversions was examined the ratio of de novo occurrences in male:female germ cells was 69:1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Brinke, A., Tagliavacca, L., Naylor, J., Green, P., Giangrande, P., Giannelli, F. <strong>Two chimaeric transcription units result from an inversion breaking intron 1 of the factor VIII gene and a region reportedly affected by reciprocal translocations in T-cell leukaemia.</strong> Hum. Molec. Genet. 5: 1945-1951, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968748</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1945" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968748">Brinke et al. (1996)</a> reported the presence of a novel inversion in 2 hemophilic monozygotic twins. These patients showed an inversion that affects the first intron of the F8 gene, displacing the most telomeric exon (exon 1) of F8 further towards the telomere and close to the C6.1A gene (BRCC3; <a href="/entry/300617">300617</a>). <a href="#23" class="mim-tip-reference" title="Brinke, A., Tagliavacca, L., Naylor, J., Green, P., Giangrande, P., Giannelli, F. <strong>Two chimaeric transcription units result from an inversion breaking intron 1 of the factor VIII gene and a region reportedly affected by reciprocal translocations in T-cell leukaemia.</strong> Hum. Molec. Genet. 5: 1945-1951, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968748</a>] [<a href="https://doi.org/10.1093/hmg/5.12.1945" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8968748">Brinke et al. (1996)</a> noted that this novel inversion creates 2 hybrid transcription units. One of these is formed by the promoter and first exon of F8 and widely expressed sequences that map telomeric to the C6.1A sequence. The other hybrid transcription unit contains the CpG island and all of the known sequence of C6.1A and the 3-prime section of most of the F8 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8968748" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>It is hypothesized that the inversion mutations occur almost exclusively in germ cells during meiotic cell division by an intrachromosomal recombination between a 9.6-kb sequence within intron 22 and 1 of 2 almost identical copies located about 300 kb distal to the F8 gene at the telomeric end of the X chromosome. Most inversion mutations originate in male germ cells, where the lack of bivalent formation may facilitate flipping of the telomeric end of the single X chromosome. <a href="#102" class="mim-tip-reference" title="Oldenburg, J., Rost, S., El-Maarri, O., Leuer, M., Olek, K., Muller, C. R., Schwaab, R. <strong>De novo factor VIII gene intron 22 inversion in a female carrier presents as a somatic mosaicism.</strong> Blood 96: 2905-2906, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11023529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11023529</a>]" pmid="11023529">Oldenburg et al. (2000)</a> reported the first instance of intron 22 inversion presenting as somatic mosaicism in a female, affecting only about 50% of lymphocyte and fibroblast cells of the proposita. Supposing a postzygotic de novo mutation as the usual cause of somatic mosaicism, the finding implies that the intron 22 inversion mutation is not restricted to meiotic cell divisions but can also occur during mitotic cell divisions, either in germ cell precursors or in somatic cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11023529" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Hemophilia A with Inhibitors</em></strong></p><p>
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Approximately 10 to 20% of patients with severe hemophilia A develop antibodies, known as inhibitors, to factor VIII following treatment with exogenous factor VIII. Most of these patients have nonsense mutations or deletions in the F8 gene (<a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al., 1995</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Antonarakis, S. E., Copeland, K. L., Carpenter, R. J., Jr., Carta, C. A., Hoyer, L. W., Caskey, C. T., Toole, J. J., Kazazian, H. H., Jr. <strong>Prenatal diagnosis of haemophilia A by factor VIII gene analysis.</strong> Lancet 325: 1407-1409, 1985. Note: Originally Volume I.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2861360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2861360</a>] [<a href="https://doi.org/10.1016/s0140-6736(85)91842-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2861360">Antonarakis et al. (1985)</a> identified several molecular defects in families with hemophilia A. One family had a deletion of about 80 kb in the F8 gene, whereas another had a single nucleotide change in the coding region of the gene, resulting in a nonsense codon and premature termination. In addition, they used 2 common polymorphic sites in the F8 gene to differentiate the normal gene from the defective gene in 4 of 6 obligate carriers from families with patients in whom inhibitors did not develop. In both the family with a large deletion and the family with premature termination, affected persons developed inhibitors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2861360" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>A variety of F8 gene mutations have been found in patients with hemophilia A due to inhibitors. Among 30 such cases, <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> found that 87 and 13% had different nonsense and missense mutations, respectively. F8 gene inversions do not seem to be a major predisposing factor for the development of inhibitors. Among severe hemophilia A cases, 16% of those without inversions and 20% of those with inversions developed inhibitors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#119" class="mim-tip-reference" title="Schwaab, R., Brackmann, H.-H., Meyer, C., Seehafer, J., Kirchgesser, M., Haack, A., Olek, K., Tuddenham, E. G. D., Oldenburg, J. <strong>Haemophilia A: mutation type determines risk of inhibitor formation.</strong> Thromb. Haemost. 74: 1402-1406, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8772209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8772209</a>]" pmid="8772209">Schwaab et al. (1995)</a> found that the probability of developing factor VIII inhibitors is greater in patients with large deletions in the F8 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8772209" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#133" class="mim-tip-reference" title="Viel, K. R., Ameri, A., Abshire, T. C., Iyer, R. V., Watts, R. G., Lutcher, C., Channell, C., Cole, S. A., Fernstrom, K. M., Nakaya, S., Kasper, C. K., Thompson, A. R., Almasy, L., Howard, T. E. <strong>Inhibitors of factor VIII in black patients with hemophilia.</strong> New Eng. J. Med. 360: 1618-1627, 2009. Note: Erratum: New Eng. J. Med. 361: 544 only, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19369668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19369668</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19369668[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1056/NEJMoa075760" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19369668">Viel et al. (2009)</a> sequenced the F8 gene in 78 black patients with hemophilia to identify the causative mutations and background haplotypes, which the authors designated H1 to H5. They found that 24% of the patients had an H3 or H4 haplotype, and that the prevalence of inhibitors was higher among patients with either of those haplotypes than among patients with haplotypes H1 or H2 (odds ratio, 3.6; p = 0.04), despite a similar spectrum of hemophilic mutations and degree of severity of illness in the 2 subgroups. Noting that Caucasians carry only the H1 or H2 haplotypes and that most blood donors are Caucasian, <a href="#133" class="mim-tip-reference" title="Viel, K. R., Ameri, A., Abshire, T. C., Iyer, R. V., Watts, R. G., Lutcher, C., Channell, C., Cole, S. A., Fernstrom, K. M., Nakaya, S., Kasper, C. K., Thompson, A. R., Almasy, L., Howard, T. E. <strong>Inhibitors of factor VIII in black patients with hemophilia.</strong> New Eng. J. Med. 360: 1618-1627, 2009. Note: Erratum: New Eng. J. Med. 361: 544 only, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19369668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19369668</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19369668[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1056/NEJMoa075760" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19369668">Viel et al. (2009)</a> suggested that mismatched factor VIII replacement therapy might be a risk factor for the development of anti-factor VIII alloantibodies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19369668" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Thrombophilia, X-Linked, due to Factor VIII Defect</em></strong></p><p>
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<a href="#121" class="mim-tip-reference" title="Shen, W., Gu, Y., Zhu, R., Zhang, L., Zhang, J., Ying, C. <strong>Copy number variations of the F8 gene are associated with venous thromboembolism.</strong> Blood Cells Molec. Dis. 50: 259-262, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23403259/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23403259</a>] [<a href="https://doi.org/10.1016/j.bcmd.2013.01.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23403259">Shen et al. (2013)</a> evaluated F8 activity and F8 gene copy number in 179 patients with venous thromboembolism and 176 healthy controls. Patients with venous thromboembolism had significantly higher F8 activity compared to controls and also had a significantly greater number of copies of the F8 gene. F8 activity was also correlated to F8 gene copy number in patients versus controls, although this was not true for every individual patient. The F8 copy number was significantly higher in males compared to females. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23403259" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 7 individuals from 2 Italian families with thrombophilia (THPH13; <a href="/entry/301071">301071</a>), <a href="#123" class="mim-tip-reference" title="Simioni, P., Cagnin, S., Sartorello, F., Sales, G., Pagani, L., Bulato, C., Gavasso, S., Nuzzo, F., Chemello, F., Radu, C. M., Tormene, D., Spiezia, L., Hackeng, T. M., Campello, E., Castoldi, E. <strong>Partial F8 gene duplication (factor VIII Padua) associated with high factor VIII levels and familial thrombophilia.</strong> Blood 137: 2383-2393, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33275657/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33275657</a>] [<a href="https://doi.org/10.1182/blood.2020008168" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33275657">Simioni et al. (2021)</a> identified a tandem duplication in the factor VIII gene (<a href="#0272">300841.0272</a>). The 2 families shared a 3-Mb haplotype, indicating a shared common ancestor. F8 mRNA was increased in patient lymphocytes. Increased transcriptional activity of fragments of the duplicated region was demonstrated by luciferase assay and was highest in a region (region C) that overlapped a major DNase I hypersensitivity cluster. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33275657" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a Japanese family with mild to moderately severe hemophilia A, <a href="#139" class="mim-tip-reference" title="Young, M., Inaba, H., Hoyer, L. W., Higuchi, M., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>Partial correction of a severe molecular defect in hemophilia A, because of errors during expression of the factor VIII gene.</strong> Am. J. Hum. Genet. 60: 565-573, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9042915/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9042915</a>]" pmid="9042915">Young et al. (1997)</a> found a deletion of a single nucleotide T within an A(8)TA(2) sequence of exon 14 of the F8 gene. The severity of the clinical phenotype did not correspond to that expected of a frameshift mutation. A small amount of functional factor VIII protein was detected in the patient's plasma. Analysis of DNA and RNA molecules from normal and affected individuals and in vitro transcription/translation suggested a partial correction of the molecular defect, because of the following: (i) DNA replication/RNA transcription errors resulted in restoration of the reading frame and/or (ii) 'ribosomal frameshifting' resulted in the production of normal factor VIII polypeptide and, thus, in a milder-than-expected hemophilia A. All of these mechanisms probably were promoted by the longer run of adenines, A(10) instead of A(8)TA(2), after the deleted T. <a href="#139" class="mim-tip-reference" title="Young, M., Inaba, H., Hoyer, L. W., Higuchi, M., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>Partial correction of a severe molecular defect in hemophilia A, because of errors during expression of the factor VIII gene.</strong> Am. J. Hum. Genet. 60: 565-573, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9042915/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9042915</a>]" pmid="9042915">Young et al. (1997)</a> concluded that errors in the complex steps of gene expression therefore may partially correct a severe frameshift defect and ameliorate an expected severe phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9042915" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#31" class="mim-tip-reference" title="Cutler, J. A., Mitchell, M. J., Smith, M. P., Savidge, G. F. <strong>The identification and classification of 41 novel mutations in the factor VIII gene (F8C).</strong> Hum. Mutat. 19: 274-278, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11857744/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11857744</a>] [<a href="https://doi.org/10.1002/humu.10056" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11857744">Cutler et al. (2002)</a> identified 81 mutations in the F8C gene in 96 unrelated patients, all of whom had previously typed negative for the common IVS22 inversion mutation (<a href="#0067">300841.0067</a>). Forty-one of these mutations were not recorded in F8C gene mutation databases. Analysis of these 41 mutations with regard to location, possible cross-species conservation, and type of substitution, in correlation with the clinical severity of the disease, supported the view that the phenotypic result of a mutation in the F8C gene correlates more with the position of the amino acid change within the 3-dimensional structure of the protein than with the actual nature of the alteration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11857744" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Early Mutation Detection Methods</em></strong></p><p>
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Since point mutations in the F8 gene are responsible for most cases of hemophilia A and only a small proportion of these mutations could be recognized by restriction endonuclease analysis, <a href="#128" class="mim-tip-reference" title="Traystman, M. D., Higuchi, M., Kasper, C. K., Antonarakis, S. E., Kazazian, H. H., Jr. <strong>Use of denaturing gradient gel electrophoresis to detect point mutations in the factor VIII gene.</strong> Genomics 6: 293-301, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2106480/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2106480</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90569-g" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2106480">Traystman et al. (1990)</a> used PCR and denaturing gradient gel electrophoresis (DGGE) to characterize single nucleotide substitutions. A GC clamp was attached to the 5-prime PCR primer to allow detection of most single base changes in DNA fragments ranging in size from 249 to 356 bp. (A 'GC clamp' is a sequence rich in G and C such that it is relatively resistant to melting by heating; see Myers et al. (<a href="#91" class="mim-tip-reference" title="Myers, R. M., Fischer, S. G., Lerman, L. S., Maniatis, T. <strong>Nearly all single base substitutions in DNA fragments joined to a GC-clamp can be detected by denaturing gradient gel electrophoresis.</strong> Nucleic Acids Res. 13: 3131-3145, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4000972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4000972</a>] [<a href="https://doi.org/10.1093/nar/13.9.3131" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4000972">1985</a>, <a href="#92" class="mim-tip-reference" title="Myers, R. M., Fischer, S. G., Maniatis, T., Lerman, L. S. <strong>Modification of the melting properties of duplex DNA by attachment of a GC-rich DNA sequence as determined by denaturing gradient gel electrophoresis.</strong> Nucleic Acids Res. 13: 3111-3129, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2987873/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2987873</a>] [<a href="https://doi.org/10.1093/nar/13.9.3111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2987873">1985</a>) and <a href="#1" class="mim-tip-reference" title="Abrams, E. S., Murdaugh, S. E., Lerman, L. S. <strong>Comprehensive detection of single base changes in human genomic DNA using denaturing gradient gel electrophoresis and a GC clamp.</strong> Genomics 7: 463-475, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2387581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2387581</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90188-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2387581">Abrams et al., 1990</a>.) Ten of 11 known point mutations were definitively separated. <a href="#128" class="mim-tip-reference" title="Traystman, M. D., Higuchi, M., Kasper, C. K., Antonarakis, S. E., Kazazian, H. H., Jr. <strong>Use of denaturing gradient gel electrophoresis to detect point mutations in the factor VIII gene.</strong> Genomics 6: 293-301, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2106480/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2106480</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90569-g" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2106480">Traystman et al. (1990)</a> then used these methods, applied to exon 8, the 3-prime end of exon 14, exon 17, exon 18, and exon 24, in a study of 52 patients with unknown mutations. A 'new' disease-producing mutation was found in 2 of the patients: a missense mutation in exon 14 (tyr1709-to-cys and asn1922-to-asp). A previously described mutation in exon 24 (arg2209-to-gln) In addition, a new polymorphic nucleotide substitution was found in intron 7. <a href="#128" class="mim-tip-reference" title="Traystman, M. D., Higuchi, M., Kasper, C. K., Antonarakis, S. E., Kazazian, H. H., Jr. <strong>Use of denaturing gradient gel electrophoresis to detect point mutations in the factor VIII gene.</strong> Genomics 6: 293-301, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2106480/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2106480</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90569-g" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2106480">Traystman et al. (1990)</a> detected all of these mutations when the GC-clamped products from all 5 regions were run in the same denaturing gel. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2106480+4000972+2987873+2387581" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#71" class="mim-tip-reference" title="Kogan, S., Gitschier, J. <strong>Mutations and a polymorphism in the factor VIII gene discovered by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 87: 2092-2096, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2107542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2107542</a>] [<a href="https://doi.org/10.1073/pnas.87.6.2092" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2107542">Kogan and Gitschier (1990)</a> likewise used DGGE to identify mutations and found a DNA polymorphism, located in intron 7, which they thought might be useful for genetic prediction in cases in which the BclI and XbaI polymorphisms are uninformative. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2107542" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a> pointed out that whereas nearly all mutations resulting in mild to moderate hemophilia B could be detected by PCR and DGGE, these methods sufficed in only 16 of 30 (53%) patients with severe hemophilia A. They interpreted this to indicate that the mutations in DNA sequence lay outside the regions studied and may include locus-controlling regions, other sequences within introns or outside the gene that are important for its expression, or perhaps another gene involved in factor VIII expression that is very closely linked to the F8 gene. <a href="#54" class="mim-tip-reference" title="Higuchi, M., Antonarakis, S. E., Kasch, L., Oldenburg, J., Economou-Petersen, E., Olek, K., Arai, M., Inaba, H., Kazazian, H. H., Jr. <strong>Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 88: 8307-8311, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1924291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1924291</a>] [<a href="https://doi.org/10.1073/pnas.88.19.8307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1924291">Higuchi et al. (1991)</a> designed a total of 45 primer sets to amplify 99% of the coding region of the F8C gene and 41 of 50 splice junctions. After PCR amplification they used denaturing gradient gel electrophoresis (DGGE) to identify successfully the point mutations in 26 DNAs with different previously identified changes. Among 29 patients with unknown mutations, they identified the disease-producing change in 25 (86%). Two polymorphisms and 2 rare normal variants were also found. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1924291+1908096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#96" class="mim-tip-reference" title="Naylor, J. A., Green, P. M., Rizza, C. R., Giannelli, F. <strong>Factor VIII gene explains all cases of haemophilia A.</strong> Lancet 340: 1066-1067, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1357455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1357455</a>] [<a href="https://doi.org/10.1016/0140-6736(92)93080-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1357455">Naylor et al. (1992)</a> used an mRNA-based method to examine hemophilia A mutations and were able to explain the report of <a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a> that mutations could not be identified in 14 of 30 severely affected patients, although mutations were found in all but 1 of 17 less severely affected patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1357455+1908096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>272 Selected Examples</a>):</strong>
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<a href="/allelicVariants/300841" class="btn btn-default" role="button"> Table View </a>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=300841[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852354 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852354;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852354" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852354" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010797" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010797" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010797</a>
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<p><a href="#46" class="mim-tip-reference" title="Gitschier, J., Wood, W. I., Tuddenham, E. G. D., Shuman, M. A., Goralka, T. M., Chen, E. Y., Lawn, R. M. <strong>Detection and sequence of mutations in the factor VIII gene of haemophiliacs.</strong> Nature 315: 427-430, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2987704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2987704</a>] [<a href="https://doi.org/10.1038/315427a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2987704">Gitschier et al. (1985)</a> identified this mutation due to a CGA-to-TGA change in codon 2326 in exon 26 in a patient with severe hemophilia A (<a href="/entry/306700">306700</a>). Nonsense mutations and a different missense (arg-to-gln) mutation have previously been observed in the same codon. It was pointed out that the G-to-T transversion is contrary to the rule of CG-to-TG mutations at CG dinucleotides, which represent the overwhelming majority. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2987704" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852355 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852355;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852355" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852355" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010798 OR RCV003656621" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010798, RCV003656621" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010798...</a>
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<p>In a severe case of hemophilia A (<a href="/entry/306700">306700</a>), <a href="#46" class="mim-tip-reference" title="Gitschier, J., Wood, W. I., Tuddenham, E. G. D., Shuman, M. A., Goralka, T. M., Chen, E. Y., Lawn, R. M. <strong>Detection and sequence of mutations in the factor VIII gene of haemophiliacs.</strong> Nature 315: 427-430, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2987704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2987704</a>] [<a href="https://doi.org/10.1038/315427a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2987704">Gitschier et al. (1985)</a> found change in codon 2228 in exon 24 from CGA to TGA to result in conversion of arg2209 to stop. This mutation has also been found by others (<a href="#144" class="mim-tip-reference" title="Youssoufian, H., Kazazian, H. H., Jr., Phillips, D. G., Aronis, S., Tsiftis, G., Brown, V. A., Antonarakis, S. E. <strong>Recurrent mutations in haemophilia A give evidence for CpG mutation hotspots.</strong> Nature 324: 380-382, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3097553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3097553</a>] [<a href="https://doi.org/10.1038/324380a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3097553">Youssoufian et al., 1986</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2987704+3097553" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 HEMOPHILIA A</strong>
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F8, EX26DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010799" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010799" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010799</a>
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#46" class="mim-tip-reference" title="Gitschier, J., Wood, W. I., Tuddenham, E. G. D., Shuman, M. A., Goralka, T. M., Chen, E. Y., Lawn, R. M. <strong>Detection and sequence of mutations in the factor VIII gene of haemophiliacs.</strong> Nature 315: 427-430, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2987704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2987704</a>] [<a href="https://doi.org/10.1038/315427a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2987704">Gitschier et al. (1985)</a> found deletion of about 22 kb including exon 26. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2987704" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852356 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852356;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852356?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010800 OR RCV002284167" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010800, RCV002284167" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010800...</a>
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<p>In a case of severe hemophilia A (<a href="/entry/306700">306700</a>) (JH5), <a href="#144" class="mim-tip-reference" title="Youssoufian, H., Kazazian, H. H., Jr., Phillips, D. G., Aronis, S., Tsiftis, G., Brown, V. A., Antonarakis, S. E. <strong>Recurrent mutations in haemophilia A give evidence for CpG mutation hotspots.</strong> Nature 324: 380-382, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3097553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3097553</a>] [<a href="https://doi.org/10.1038/324380a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3097553">Youssoufian et al. (1986)</a> found change of codon 2135 from CGA to TGA, resulting in conversion of amino acid 2116 to stop. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3097553" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0005" class="mim-anchor"></a>
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<strong>.0005 HEMOPHILIA A</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010801" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010801" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010801</a>
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<p>In a case of severe hemophilia A (<a href="/entry/306700">306700</a>) (JH6), <a href="#140" class="mim-tip-reference" title="Youssoufian, H., Antonarakis, S. E., Aronis, S., Tsiftis, G., Phillips, D. G., Kazazian, H. H., Jr. <strong>Characterization of five partial deletions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 84: 3772-3776, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3035554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3035554</a>] [<a href="https://doi.org/10.1073/pnas.84.11.3772" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3035554">Youssoufian et al. (1987)</a> found deletion of exon 6. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3035554" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with severe hemophilia A (patient 2213), <a href="#77" class="mim-tip-reference" title="Levinson, B., Kenwrick, S., Lakich, D., Hammonds, G., Gitschier, J. <strong>A transcribed gene in an intron of the human factor VIII gene.</strong> Genomics 7: 1-11, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2110545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2110545</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90512-s" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2110545">Levinson et al. (1990)</a> found a deletion of exon 6 of the factor VIII gene. <a href="#120" class="mim-tip-reference" title="Schwaab, R., Oldenburg, J., Tuddenham, E. G. D., Brackmann, H. H., Olek, K. <strong>Mutations in haemophilia A.</strong> Brit. J. Haemat. 83: 450-458, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8485051/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8485051</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1993.tb04670.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8485051">Schwaab et al. (1993)</a> identified 2 patients with this deletion. See also <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> and <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8485051+2110545+7728145+8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0006 HEMOPHILIA A</strong>
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</h4>
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F8, EX14DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010802" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010802" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010802</a>
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<p>In a case of severe hemophilia A (<a href="/entry/306700">306700</a>) (JH7), <a href="#140" class="mim-tip-reference" title="Youssoufian, H., Antonarakis, S. E., Aronis, S., Tsiftis, G., Phillips, D. G., Kazazian, H. H., Jr. <strong>Characterization of five partial deletions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 84: 3772-3776, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3035554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3035554</a>] [<a href="https://doi.org/10.1073/pnas.84.11.3772" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3035554">Youssoufian et al. (1987)</a> found deletion of exon 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3035554" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 patients with severe hemophilia A, <a href="#72" class="mim-tip-reference" title="Krepelova, A., Vorlova, Z., Zavadil, J., Brdicka, R. <strong>Factor VIII gene deletions in haemophilia A patients in Czechoslovakia.</strong> Brit. J. Haemat. 81: 271-276, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1643024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1643024</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1992.tb08219.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1643024">Krepelova et al. (1992)</a> found a deletion of exon 14 of the factor VIII gene. See also <a href="#0029">300841.0029</a>, <a href="#0047">300841.0047</a>, and <a href="#0049">300841.0049</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1643024" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0007" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0007 HEMOPHILIA A</strong>
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</h4>
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F8, EX24-25DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010803" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010803" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010803</a>
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<p>In a case of severe hemophilia A (<a href="/entry/306700">306700</a>) (JH8), <a href="#140" class="mim-tip-reference" title="Youssoufian, H., Antonarakis, S. E., Aronis, S., Tsiftis, G., Phillips, D. G., Kazazian, H. H., Jr. <strong>Characterization of five partial deletions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 84: 3772-3776, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3035554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3035554</a>] [<a href="https://doi.org/10.1073/pnas.84.11.3772" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3035554">Youssoufian et al. (1987)</a> found deletion of exons 24 and 25. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3035554" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0008" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0008 HEMOPHILIA A</strong>
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F8, EX23-25DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010804" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010804" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010804</a>
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<p>In a case of severe hemophilia A (<a href="/entry/306700">306700</a>) (JH9), <a href="#140" class="mim-tip-reference" title="Youssoufian, H., Antonarakis, S. E., Aronis, S., Tsiftis, G., Phillips, D. G., Kazazian, H. H., Jr. <strong>Characterization of five partial deletions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 84: 3772-3776, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3035554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3035554</a>] [<a href="https://doi.org/10.1073/pnas.84.11.3772" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3035554">Youssoufian et al. (1987)</a> found deletion of exons 23-25. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3035554" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0009" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0009 HEMOPHILIA A</strong>
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F8, EX22DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010805" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010805" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010805</a>
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<p>In a case of moderately severe hemophilia A (<a href="/entry/306700">306700</a>) (JH10), <a href="#140" class="mim-tip-reference" title="Youssoufian, H., Antonarakis, S. E., Aronis, S., Tsiftis, G., Phillips, D. G., Kazazian, H. H., Jr. <strong>Characterization of five partial deletions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 84: 3772-3776, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3035554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3035554</a>] [<a href="https://doi.org/10.1073/pnas.84.11.3772" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3035554">Youssoufian et al. (1987)</a> found 'in-frame' deletion of exon 22. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3035554" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0010" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0010 HEMOPHILIA A</strong>
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</h4>
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F8, EX26DEL
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010806" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010806" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010806</a>
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<p>In a case of severe hemophilia A (<a href="/entry/306700">306700</a>) (JH12), <a href="#8" class="mim-tip-reference" title="Antonarakis, S. E., Rossiter, J. P., Young, M., Horst, J., de Moerloose, P., Sommer, S. S., Ketterling, R. P., Kazazian, H. H., Jr., Negrier, C., Vinciguerra, C., Gitschier, J., Goossens, M., and 54 others. <strong>Factor VIII inversions in severe hemophilia A: results from an international consortium.</strong> Blood 86: 2206-2212, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7662970/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7662970</a>]" pmid="7662970">Antonarakis et al. (1995)</a> found deletion of exon 26. The mother showed mosaicism for this mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7662970" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0011" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0011 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, EX1DEL
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010807" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010807" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010807</a>
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<span class="mim-text-font">
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<p>In a case of severe hemophilia A (<a href="/entry/306700">306700</a>) (JH13), <a href="#141" class="mim-tip-reference" title="Youssoufian, H., Antonarakis, S. E., Bell, W., Griffin, A. M., Kazazian, H. H., Jr. <strong>Nonsense and missense mutations in hemophilia A: estimate of the relative mutation rate at CG dinucleotides.</strong> Am. J. Hum. Genet. 42: 718-725, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2833855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2833855</a>]" pmid="2833855">Youssoufian et al. (1988)</a> found deletion of exon 1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2833855" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with severe hemophilia A (patient H309), <a href="#87" class="mim-tip-reference" title="Millar, D. S., Steinbrecher, R. A., Wieland, K., Grundy, C. B., Martinowitz, U., Krawczak, M., Zoll, B., Whitmore, D., Stephenson, J., Mibashan, R. S., Kakkar, V. V., Cooper, D. N. <strong>The molecular genetic analysis of haemophilia A: characterization of six partial deletions in the factor VIII gene.</strong> Hum. Genet. 86: 219-227, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2125022/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2125022</a>] [<a href="https://doi.org/10.1007/BF00197709" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2125022">Millar et al. (1990)</a> found a deletion of exon 1 of the factor VIII gene. See also <a href="#134" class="mim-tip-reference" title="Wehnert, M., Herrmann, F. H., Wulff, K. <strong>Partial deletions of factor VIII gene as molecular diagnostic markers in hemophilia A.</strong> Dis. Markers 7: 113-117, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2567219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2567219</a>]" pmid="2567219">Wehnert et al. (1989)</a>, <a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a>, <a href="#120" class="mim-tip-reference" title="Schwaab, R., Oldenburg, J., Tuddenham, E. G. D., Brackmann, H. H., Olek, K. <strong>Mutations in haemophilia A.</strong> Brit. J. Haemat. 83: 450-458, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8485051/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8485051</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1993.tb04670.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8485051">Schwaab et al. (1993)</a>, and <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a>, who reported patients with deletion of exon 1. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7728145+2567219+1908096+8485051+2125022" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852357 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852357;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852357" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852357" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010808" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010808" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010808</a>
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<p>In a case of severe hemophilia A (<a href="/entry/306700">306700</a>) (JH14), <a href="#141" class="mim-tip-reference" title="Youssoufian, H., Antonarakis, S. E., Bell, W., Griffin, A. M., Kazazian, H. H., Jr. <strong>Nonsense and missense mutations in hemophilia A: estimate of the relative mutation rate at CG dinucleotides.</strong> Am. J. Hum. Genet. 42: 718-725, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2833855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2833855</a>]" pmid="2833855">Youssoufian et al. (1988)</a> found a CGA to TGA change in codon 2166, resulting in a change in ARG2147 to a termination codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2833855" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs387906429 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906429;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs387906429?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906429" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906429" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010809 OR RCV003407314" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010809, RCV003407314" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010809...</a>
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<p>In a case of mild hemophilia A (<a href="/entry/306700">306700</a>) (JH17), <a href="#141" class="mim-tip-reference" title="Youssoufian, H., Antonarakis, S. E., Bell, W., Griffin, A. M., Kazazian, H. H., Jr. <strong>Nonsense and missense mutations in hemophilia A: estimate of the relative mutation rate at CG dinucleotides.</strong> Am. J. Hum. Genet. 42: 718-725, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2833855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2833855</a>]" pmid="2833855">Youssoufian et al. (1988)</a> found the creation of a new splice donor site created in intron 4 by a GAA to AAA change. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2833855" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852358 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852358;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852358" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852358" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010810 OR RCV000852189" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010810, RCV000852189" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010810...</a>
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<p>In 2 cases of severe hemophilia A (<a href="/entry/306700">306700</a>) (JH18, JH19), <a href="#141" class="mim-tip-reference" title="Youssoufian, H., Antonarakis, S. E., Bell, W., Griffin, A. M., Kazazian, H. H., Jr. <strong>Nonsense and missense mutations in hemophilia A: estimate of the relative mutation rate at CG dinucleotides.</strong> Am. J. Hum. Genet. 42: 718-725, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2833855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2833855</a>]" pmid="2833855">Youssoufian et al. (1988)</a> found a CGA-to-CAA change in codon 2228, resulting in substitution of glutamine for arginine as amino acid 2209. This mutation has also been found by others (<a href="#18" class="mim-tip-reference" title="Bernardi, F., Volinia, S., Patracchini, P., Gemmati, D., Boninsegna, S., Schwienbacher, C., Marchetti, G. <strong>A recurrent missense mutation (arg-to-gln) and a partial deletion in factor VIII gene causing severe haemophilia A.</strong> Brit. J. Haemat. 71: 271-276, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2493803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2493803</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1989.tb04266.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2493803">Bernardi et al., 1989</a>; <a href="#78" class="mim-tip-reference" title="Levinson, B., Lehesjoki, A.-E., de la Chapelle, A., Gitschier, J. <strong>Molecular analysis of hemophilia A mutations in the Finnish population.</strong> Am. J. Hum. Genet. 46: 53-62, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2104741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2104741</a>]" pmid="2104741">Levinson et al., 1990</a>; <a href="#128" class="mim-tip-reference" title="Traystman, M. D., Higuchi, M., Kasper, C. K., Antonarakis, S. E., Kazazian, H. H., Jr. <strong>Use of denaturing gradient gel electrophoresis to detect point mutations in the factor VIII gene.</strong> Genomics 6: 293-301, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2106480/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2106480</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90569-g" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2106480">Traystman et al., 1990</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2833855+2493803+2106480+2104741" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852359 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852359;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852359" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852359" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010811" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010811" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010811</a>
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<p><a href="#141" class="mim-tip-reference" title="Youssoufian, H., Antonarakis, S. E., Bell, W., Griffin, A. M., Kazazian, H. H., Jr. <strong>Nonsense and missense mutations in hemophilia A: estimate of the relative mutation rate at CG dinucleotides.</strong> Am. J. Hum. Genet. 42: 718-725, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2833855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2833855</a>]" pmid="2833855">Youssoufian et al. (1988)</a> demonstrated the usefulness of DNA amplification followed by direct nucleotide sequencing in the search for mutations in X-linked disorders because of the unambiguous sequencing data obtained when the amplified DNA is from a male patient. In a 17-year-old Greek male with moderately severe hemophilia A (<a href="/entry/306700">306700</a>) (JH20), they detected a mutation by analysis of genomic DNA with TaqI; contrary to previous experience, the mutation was not a C-to-T or G-to-A transition. (The unifying mechanism of these mutations is thought to be methylation-induced C-to-T transitions at CpG dinucleotides involving either the coding or the complementary strand of DNA; see <a href="#20" class="mim-tip-reference" title="Bird, A. P. <strong>DNA methylation and the frequency of CpG in animal DNA.</strong> Nucleic Acids Res. 8: 1499-1504, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6253938/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6253938</a>] [<a href="https://doi.org/10.1093/nar/8.7.1499" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6253938">Bird (1980)</a>.) In this case the point mutation was in exon 7, where codon 291 for glutamate (GAA) was changed to one for glycine (GGA), leading to a change in amino acid 272 of the mature factor VIII protein. The mutation had arisen de novo in a germ cell of the patient's mother. The patient had 2% factor VIII activity, 3.5% factor VIII antigen, and moderate hemophilia A. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2833855+6253938" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0016" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0016 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, EX2-3DEL
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010812" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010812" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010812</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a case of severe hemophilia A (<a href="/entry/306700">306700</a>) (JH21), <a href="#143" class="mim-tip-reference" title="Youssoufian, H., Kasper, C. K., Phillips, D. G., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>Restriction endonuclease mapping of six novel deletions of the factor VIII gene in hemophilia A.</strong> Hum. Genet. 80: 143-148, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3139545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3139545</a>] [<a href="https://doi.org/10.1007/BF00702857" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3139545">Youssoufian et al. (1988)</a> found deletion of exons 2 and 3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3139545" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with severe hemophilia A (patient 656), <a href="#56" class="mim-tip-reference" title="Higuchi, M., Kochhan, L., Olek, K. <strong>A somatic mosaic for haemophilia A detected at the DNA level.</strong> Molec. Biol. Med. 5: 23-27, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3131627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3131627</a>]" pmid="3131627">Higuchi et al. (1988)</a> found a deletion of exons 2-3 of the factor VIII gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3131627" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0017" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0017 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, EX3-13DEL
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010813" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010813" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010813</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a case of severe hemophilia A (<a href="/entry/306700">306700</a>) (JH22), <a href="#143" class="mim-tip-reference" title="Youssoufian, H., Kasper, C. K., Phillips, D. G., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>Restriction endonuclease mapping of six novel deletions of the factor VIII gene in hemophilia A.</strong> Hum. Genet. 80: 143-148, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3139545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3139545</a>] [<a href="https://doi.org/10.1007/BF00702857" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3139545">Youssoufian et al. (1988)</a> found deletion of exons 3-13. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3139545" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0018" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0018 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, EX4-25DEL
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010814" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010814" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010814</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In a case of severe hemophilia A (<a href="/entry/306700">306700</a>) (JH23), <a href="#143" class="mim-tip-reference" title="Youssoufian, H., Kasper, C. K., Phillips, D. G., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>Restriction endonuclease mapping of six novel deletions of the factor VIII gene in hemophilia A.</strong> Hum. Genet. 80: 143-148, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3139545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3139545</a>] [<a href="https://doi.org/10.1007/BF00702857" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3139545">Youssoufian et al. (1988)</a> found deletion of exons 4-25. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3139545" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0019" class="mim-anchor"></a>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0019 HEMOPHILIA A</strong>
|
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</span>
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, EX7-14DEL
|
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</div>
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</span>
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<span class="mim-text-font">
|
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010815" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010815" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010815</a>
|
|
</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a case of severe hemophilia A (<a href="/entry/306700">306700</a>) (JH24), <a href="#143" class="mim-tip-reference" title="Youssoufian, H., Kasper, C. K., Phillips, D. G., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>Restriction endonuclease mapping of six novel deletions of the factor VIII gene in hemophilia A.</strong> Hum. Genet. 80: 143-148, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3139545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3139545</a>] [<a href="https://doi.org/10.1007/BF00702857" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3139545">Youssoufian et al. (1988)</a> found deletion of exons 7-14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3139545" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0020" class="mim-anchor"></a>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0020 FACTOR VIII POLYMORPHISM</strong>
|
|
</span>
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
|
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F8, LINE INS, IVS10
|
|
</div>
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</span>
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<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010816" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010816" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010816</a>
|
|
</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a normal individual (JH25), <a href="#137" class="mim-tip-reference" title="Woods-Samuels, P., Wong, C., Mathias, S. L., Scott, A. F., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>Characterization of a nondeleterious L1 insertion in an intron of the human factor VIII gene and further evidence of open reading frames in functional L1 elements.</strong> Genomics 4: 290-296, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2497061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2497061</a>] [<a href="https://doi.org/10.1016/0888-7543(89)90332-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2497061">Woods-Samuels et al. (1989)</a> found insertion of 0.7 kb of LINE sequence in intron 10. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2497061" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0021" class="mim-anchor"></a>
|
|
<h4>
|
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<span class="mim-font">
|
|
<strong>.0021 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
|
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F8, EX26DEL
|
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</div>
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</span>
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<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010817" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010817" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010817</a>
|
|
</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) (JH26), <a href="#143" class="mim-tip-reference" title="Youssoufian, H., Kasper, C. K., Phillips, D. G., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>Restriction endonuclease mapping of six novel deletions of the factor VIII gene in hemophilia A.</strong> Hum. Genet. 80: 143-148, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3139545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3139545</a>] [<a href="https://doi.org/10.1007/BF00702857" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3139545">Youssoufian et al. (1988)</a> found deletion of exon 26. Also see <a href="#46" class="mim-tip-reference" title="Gitschier, J., Wood, W. I., Tuddenham, E. G. D., Shuman, M. A., Goralka, T. M., Chen, E. Y., Lawn, R. M. <strong>Detection and sequence of mutations in the factor VIII gene of haemophiliacs.</strong> Nature 315: 427-430, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2987704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2987704</a>] [<a href="https://doi.org/10.1038/315427a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2987704">Gitschier et al. (1985)</a> and <a href="#18" class="mim-tip-reference" title="Bernardi, F., Volinia, S., Patracchini, P., Gemmati, D., Boninsegna, S., Schwienbacher, C., Marchetti, G. <strong>A recurrent missense mutation (arg-to-gln) and a partial deletion in factor VIII gene causing severe haemophilia A.</strong> Brit. J. Haemat. 71: 271-276, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2493803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2493803</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1989.tb04266.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2493803">Bernardi et al. (1989)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2493803+3139545+2987704" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0022" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 HEMOPHILIA A</strong>
|
|
</span>
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, LINE INS, EX14
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</div>
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</span>
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<span class="mim-text-font">
|
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010818" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010818" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010818</a>
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|
</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In 2 brothers with severe hemophilia A (<a href="/entry/306700">306700</a>) (JH27, JH28), <a href="#68" class="mim-tip-reference" title="Kazazian, H. H., Jr., Wong, C., Youssoufian, H., Scott, A. F., Phillips, D. G., Antonarakis, S. E. <strong>Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in man.</strong> Nature 332: 164-166, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2831458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2831458</a>] [<a href="https://doi.org/10.1038/332164a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2831458">Kazazian et al. (1988)</a> found insertion of 3.8 kb of LINE sequence in exon 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2831458" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0023" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0023 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
|
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<div style="float: left;">
|
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F8, EX15DEL
|
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</div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010819" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010819" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010819</a>
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<p>In a patient (JH29) with severe hemophilia A (<a href="/entry/306700">306700</a>) and a translocation t(X;17), <a href="#8" class="mim-tip-reference" title="Antonarakis, S. E., Rossiter, J. P., Young, M., Horst, J., de Moerloose, P., Sommer, S. S., Ketterling, R. P., Kazazian, H. H., Jr., Negrier, C., Vinciguerra, C., Gitschier, J., Goossens, M., and 54 others. <strong>Factor VIII inversions in severe hemophilia A: results from an international consortium.</strong> Blood 86: 2206-2212, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7662970/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7662970</a>]" pmid="7662970">Antonarakis et al. (1995)</a> found deletion of exon 15. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7662970" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0024" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0024 HEMOPHILIA A</strong>
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F8, 2-BP DEL, EX8
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010916" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010916" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010916</a>
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) (JH31), <a href="#58" class="mim-tip-reference" title="Higuchi, M., Wong, C., Kochhan, L., Olek, K., Aronis, S., Kasper, C. K., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>Characterization of mutations in the factor VIII gene by direct sequencing of amplified genomic DNA.</strong> Genomics 6: 65-71, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2105906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2105906</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90448-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2105906">Higuchi et al. (1990)</a> found deletion of GA from codon 360 GAA in exon 8. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2105906" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0025" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0025 HEMOPHILIA A</strong>
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F8, ARG2307LEU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852360 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852360;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852360" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852360" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010821" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010821" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010821</a>
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</span>
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</div>
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<span class="mim-text-font">
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<p>In a Japanese patient with mild hemophilia A (<a href="/entry/306700">306700</a>) (JH32), <a href="#61" class="mim-tip-reference" title="Inaba, H., Fujimaki, M., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>Mild hemophilia A resulting from arg-to-leu substitution in exon 26 of the factor VIII gene.</strong> Hum. Genet. 81: 335-338, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2495245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2495245</a>] [<a href="https://doi.org/10.1007/BF00283686" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2495245">Inaba et al. (1989)</a> found a CGA-to-CTA change in codon 2326 in exon 26, resulting in substitution of leucine for arginine at amino acid 2307. PCR and nucleotide sequencing were used to identify the defect, which caused an alteration in a TaqI site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2495245" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0026" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0026 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, ARG1941GLN
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28937294 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937294;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28937294" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28937294" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010822 OR RCV000756109" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010822, RCV000756109" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010822...</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>{Antonarakis (unpublished observations)} reported a Japanese patient with mild hemophilia A (<a href="/entry/306700">306700</a>) with a CGA-to-CAA change t nucleotide 1960 in exon 18, resulting in substitution of glutamine for arginine at amino acid 1941. This mutation was also found in a Finnish patient by <a href="#77" class="mim-tip-reference" title="Levinson, B., Kenwrick, S., Lakich, D., Hammonds, G., Gitschier, J. <strong>A transcribed gene in an intron of the human factor VIII gene.</strong> Genomics 7: 1-11, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2110545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2110545</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90512-s" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2110545">Levinson et al. (1990)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2110545" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0027" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0027 FACTOR VIII (OKAYAMA)</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, ARG372HIS
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28935499 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28935499;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28935499" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28935499" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010823 OR RCV000757254 OR RCV000852002 OR RCV004812295" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010823, RCV000757254, RCV000852002, RCV004812295" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010823...</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a case of CRM-positive hemophilia A (<a href="/entry/306700">306700</a>) (JH35), <a href="#11" class="mim-tip-reference" title="Arai, M., Inaba, H., Higuchi, M., Antonarakis, S. E., Kazazian, H. H., Jr., Fujimaki, M., Hoyer, L. W. <strong>Direct characterization of factor VIII in plasma: detection of a mutation altering a thrombin cleavage site (arginine372-to-histidine).</strong> Proc. Nat. Acad. Sci. 86: 4277-4281, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2498882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2498882</a>] [<a href="https://doi.org/10.1073/pnas.86.11.4277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2498882">Arai et al. (1989)</a> found a change of arginine-372 to histidine, resulting from a CGC-to-CAC change in codon 391 in exon 8. The mutation was at the site of thrombin cleavage. <a href="#122" class="mim-tip-reference" title="Shima, M., Ware, J., Yoshioka, A., Fukui, H., Fulcher, C. A. <strong>An arginine to cysteine amino acid substitution at a critical thrombin cleavage site in a dysfunctional factor VIII molecule.</strong> Blood 74: 1612-1617, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2506948/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2506948</a>]" pmid="2506948">Shima et al. (1989)</a> found the same change in what they called factor VIII (Okayama). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2506948+2498882" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0028" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0028 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div style="float: left;">
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F8, GLU1686TER
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852361 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852361;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852361?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852361" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852361" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010824" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010824" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010824</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) (JH36), <a href="#58" class="mim-tip-reference" title="Higuchi, M., Wong, C., Kochhan, L., Olek, K., Aronis, S., Kasper, C. K., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>Characterization of mutations in the factor VIII gene by direct sequencing of amplified genomic DNA.</strong> Genomics 6: 65-71, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2105906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2105906</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90448-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2105906">Higuchi et al. (1990)</a> found a CAG-to-TAG change in codon 1705, causing replacement of glutamic acid 1686 by a stop signal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2105906" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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<div>
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<div>
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<a id="0029" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0029 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, EX14DEL
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010825" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010825" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010825</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) (JH37), <a href="#57" class="mim-tip-reference" title="Higuchi, M., Kochhan, L., Schwaab, R., Egli, H., Brackmann, H. H., Horst, J., Olek, K. <strong>Molecular defects in hemophilia A: identification and characterization of mutations in the factor VIII gene and family analysis.</strong> Blood 74: 1045-1051, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2473810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2473810</a>]" pmid="2473810">Higuchi et al. (1989)</a> found deletion of exon 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2473810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0030" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0030 HEMOPHILIA A</strong>
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FACTOR VIII (EAST HARTFORD)
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F8, ARG1689CYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs111033613 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033613;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs111033613" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs111033613" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010826 OR RCV000010827 OR RCV001092277" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010826, RCV000010827, RCV001092277" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010826...</a>
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<p>In a patient with moderately severe hemophilia A (<a href="/entry/306700">306700</a>) of a CRM-positive type, <a href="#47" class="mim-tip-reference" title="Gitschier, J. <strong>Maternal duplication associated with gene deletion in sporadic hemophilia.</strong> Am. J. Hum. Genet. 43: 274-279, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2901224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2901224</a>]" pmid="2901224">Gitschier (1988)</a> found a CGC-to-TGC change in codon 1708 in exon 14, resulting in a change of arginine-1689 to cysteine. The mutation affects the thrombin cleavage site. The same mutation was subsequently found in additional patients (JH38, JH39) by <a href="#10" class="mim-tip-reference" title="Arai, M., Higuchi, M., Antonarakis, S. E., Kazazian, H. H., Jr., Phillips, J. A., III, Janco, R. L., Hoyer, L. W. <strong>Characterization of a thrombin cleavage site mutation (arg1689-to-cys) in the factor VIII gene of two unrelated patients with cross-reacting material-positive hemophilia A.</strong> Blood 75: 384-389, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2104766/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2104766</a>]" pmid="2104766">Arai et al. (1990)</a>. <a href="#3" class="mim-tip-reference" title="Aly, A. M., Arai, M., Hoyer, L. W. <strong>Cysteamine enhances the procoagulant activity of factor VIII-East Hartford, a dysfunctional protein due to a light chain thrombin cleavage site mutation (arginine-1689 to cysteine).</strong> J. Clin. Invest. 89: 1375-1381, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1569180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1569180</a>] [<a href="https://doi.org/10.1172/JCI115725" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1569180">Aly et al. (1992)</a> found that cysteamine, which is known to modify mutant proteins with an arg-to-cys substitution, enhances the procoagulant activity of the mutant factor VIII, which they referred to as factor VIII-East Hartford. <a href="#5" class="mim-tip-reference" title="Aly, A. M., Hoyer, L. W. <strong>Factor VIII-East Hartford (arginine1689 to cysteine) has procoagulant activity when separated from von Willebrand factor.</strong> J. Clin. Invest. 89: 1382-1387, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1569181/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1569181</a>] [<a href="https://doi.org/10.1172/JCI115726" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1569181">Aly and Hoyer (1992)</a> demonstrated that the East Hartford mutant protein had procoagulant activity when separated from von Willebrand factor; this was taken to indicate that the dissociation of factor VIII from VWF is an essential effect of factor VIII light chain cleavage at arginine-1689. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2901224+2104766+1569180+1569181" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0031" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0031 HEMOPHILIA A</strong>
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F8, TYR1680PHE
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28935203 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28935203;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs28935203?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28935203" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28935203" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010828 OR RCV002508187 OR RCV004975259" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010828, RCV002508187, RCV004975259" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010828...</a>
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</span>
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<span class="mim-text-font">
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<p>In a patient with mild hemophilia A (<a href="/entry/306700">306700</a>) (JH40), <a href="#58" class="mim-tip-reference" title="Higuchi, M., Wong, C., Kochhan, L., Olek, K., Aronis, S., Kasper, C. K., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>Characterization of mutations in the factor VIII gene by direct sequencing of amplified genomic DNA.</strong> Genomics 6: 65-71, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2105906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2105906</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90448-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2105906">Higuchi et al. (1990)</a> found a TAT-to-TTT change in codon 1699, resulting in substitution of phenylalanine for tyrosine at amino acid 1680. The mutation affected the von Willebrand binding site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2105906" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0032" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0032 HEMOPHILIA A</strong>
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</h4>
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<span class="mim-text-font">
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F8, TYR1709CYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852362 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852362;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852362" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852362" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010829" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010829" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010829</a>
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<p>In a patient with hemophilia A (<a href="/entry/306700">306700</a>) (JH41), <a href="#128" class="mim-tip-reference" title="Traystman, M. D., Higuchi, M., Kasper, C. K., Antonarakis, S. E., Kazazian, H. H., Jr. <strong>Use of denaturing gradient gel electrophoresis to detect point mutations in the factor VIII gene.</strong> Genomics 6: 293-301, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2106480/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2106480</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90569-g" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2106480">Traystman et al. (1990)</a> found a TAT-to-TGT change in codon 1728 of exon 14, leading to substitution of cysteine for tyrosine-1709. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2106480" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0033" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0033 HEMOPHILIA A</strong>
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F8, EX11-22DEL
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010830" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010830" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010830</a>
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</span>
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<p>In a case of severe hemophilia A (<a href="/entry/306700">306700</a>) (JH1), <a href="#9" class="mim-tip-reference" title="Antonarakis, S. E., Waber, P. G., Kittur, S. D., Patel, A. S., Kazazian, H. H., Jr., Mellis, M. A., Counts, R. B., Stamatoyannopoulos, G., Bowie, E. J. W., Fass, D. N., Pittman, D. D., Wozney, J. M., Toole, J. J. <strong>Hemophilia A: detection of molecular defects and of carriers by DNA analysis.</strong> New Eng. J. Med. 313: 842-848, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2993888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2993888</a>] [<a href="https://doi.org/10.1056/NEJM198510033131402" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2993888">Antonarakis et al. (1985)</a> found deletion of exons 11-22. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2993888" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>(This allelic variant was originally entered into the database incorrectly as EX11-18DEL.)</p>
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<a id="0034" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0034 HEMOPHILIA A</strong>
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</span>
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</h4>
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<div style="float: left;">
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F8, ARG1960TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852363 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852363;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852363?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852363" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852363" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010831" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010831" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010831</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a case of severe hemophilia A (<a href="/entry/306700">306700</a>) (JH2), <a href="#9" class="mim-tip-reference" title="Antonarakis, S. E., Waber, P. G., Kittur, S. D., Patel, A. S., Kazazian, H. H., Jr., Mellis, M. A., Counts, R. B., Stamatoyannopoulos, G., Bowie, E. J. W., Fass, D. N., Pittman, D. D., Wozney, J. M., Toole, J. J. <strong>Hemophilia A: detection of molecular defects and of carriers by DNA analysis.</strong> New Eng. J. Med. 313: 842-848, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2993888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2993888</a>] [<a href="https://doi.org/10.1056/NEJM198510033131402" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2993888">Antonarakis et al. (1985)</a> found change in exon 18 from CGA to TGA which converted arg1960 to stop. <a href="#144" class="mim-tip-reference" title="Youssoufian, H., Kazazian, H. H., Jr., Phillips, D. G., Aronis, S., Tsiftis, G., Brown, V. A., Antonarakis, S. E. <strong>Recurrent mutations in haemophilia A give evidence for CpG mutation hotspots.</strong> Nature 324: 380-382, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3097553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3097553</a>] [<a href="https://doi.org/10.1038/324380a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3097553">Youssoufian et al. (1986)</a> found the same mutation in another case of severe hemophilia A (JH3). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3097553+2993888" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0035" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0035 HEMOPHILIA A</strong>
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</h4>
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F8, EX3DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010832" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010832" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010832</a>
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#57" class="mim-tip-reference" title="Higuchi, M., Kochhan, L., Schwaab, R., Egli, H., Brackmann, H. H., Horst, J., Olek, K. <strong>Molecular defects in hemophilia A: identification and characterization of mutations in the factor VIII gene and family analysis.</strong> Blood 74: 1045-1051, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2473810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2473810</a>]" pmid="2473810">Higuchi et al. (1989)</a> found a deletion of exon 3 about 2 kb in length. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2473810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0036" class="mim-anchor"></a>
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<strong>.0036 FACTOR VIII POLYMORPHISM</strong>
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</h4>
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F8, 7-KB DEL, IVS1
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010833" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010833" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010833</a>
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<p><a href="#78" class="mim-tip-reference" title="Levinson, B., Lehesjoki, A.-E., de la Chapelle, A., Gitschier, J. <strong>Molecular analysis of hemophilia A mutations in the Finnish population.</strong> Am. J. Hum. Genet. 46: 53-62, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2104741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2104741</a>]" pmid="2104741">Levinson et al. (1990)</a> found a deletion of 7 kb from IVS1 as a presumed normal variant of factor VIII. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2104741" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0037" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0037 HEMOPHILIA A</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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F8, EX1-5DEL
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010834" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010834" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010834</a>
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</span>
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</div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#57" class="mim-tip-reference" title="Higuchi, M., Kochhan, L., Schwaab, R., Egli, H., Brackmann, H. H., Horst, J., Olek, K. <strong>Molecular defects in hemophilia A: identification and characterization of mutations in the factor VIII gene and family analysis.</strong> Blood 74: 1045-1051, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2473810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2473810</a>]" pmid="2473810">Higuchi et al. (1989)</a> found a 35+ kb deletion removing exons 1 to 5. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2473810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0038" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0038 HEMOPHILIA A</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, EX1-22DEL
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010835" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010835" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010835</a>
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</span>
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</div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#79" class="mim-tip-reference" title="Lillicrap, D. P., Taylor, S. A. M., Grover, H., Teitel, J., Giles, A. R., Holden, J. J. A., White, B. N. <strong>Genetic analysis in hemophilia A: identification of a large F.VIII gene deletion in a patient with high titre antibodies to human and porcine F.VIII. (Abstract)</strong> Blood 68: 337a only, 1986."None>Lillicrap et al. (1986)</a> found a 127+ kb deletion that removed exons 1 to 22.</p>
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</span>
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<a id="0039" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0039 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, EX26DEL
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010836" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010836" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010836</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#57" class="mim-tip-reference" title="Higuchi, M., Kochhan, L., Schwaab, R., Egli, H., Brackmann, H. H., Horst, J., Olek, K. <strong>Molecular defects in hemophilia A: identification and characterization of mutations in the factor VIII gene and family analysis.</strong> Blood 74: 1045-1051, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2473810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2473810</a>]" pmid="2473810">Higuchi et al. (1989)</a> found deletion of exon 26. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2473810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with severe hemophilia A (patient HDX5), <a href="#18" class="mim-tip-reference" title="Bernardi, F., Volinia, S., Patracchini, P., Gemmati, D., Boninsegna, S., Schwienbacher, C., Marchetti, G. <strong>A recurrent missense mutation (arg-to-gln) and a partial deletion in factor VIII gene causing severe haemophilia A.</strong> Brit. J. Haemat. 71: 271-276, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2493803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2493803</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1989.tb04266.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2493803">Bernardi et al. (1989)</a> found a deletion of exon 26 of the factor VIII gene. This deletion was also reported by <a href="#94" class="mim-tip-reference" title="Nafa, K., Meriane, F., Reghis, A., Benabadji, M., Demenais, F., Guilloud-Bataille, M., Sultan, Y., Kaplan, J. C., Delpech, M. <strong>Investigation of factor VIIIC gene restriction fragment length polymorphisms and search for deletions in hemophiliac subjects in Algeria.</strong> Hum. Genet. 84: 401-405, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1969840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1969840</a>] [<a href="https://doi.org/10.1007/BF00195808" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1969840">Nafa et al. (1990)</a>, <a href="#74" class="mim-tip-reference" title="Lavergne, J. M., Bahnak, B. R., Vidaud, M., Laurian, Y., Meyer, D. <strong>A directed search for mutations in hemophilia A using restriction enzyme analysis and denaturing gradient gel electrophoresis: a study of seven exons in the factor VIII gene of 170 cases.</strong> Nouv. Rev. Franc. Hemat. 34: 85-91, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1523102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1523102</a>]" pmid="1523102">Lavergne et al. (1992)</a>, <a href="#120" class="mim-tip-reference" title="Schwaab, R., Oldenburg, J., Tuddenham, E. G. D., Brackmann, H. H., Olek, K. <strong>Mutations in haemophilia A.</strong> Brit. J. Haemat. 83: 450-458, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8485051/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8485051</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1993.tb04670.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8485051">Schwaab et al. (1993)</a>, and <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7728145+8485051+2493803+1523102+1969840" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div>
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<div>
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<div>
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<a id="0040" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0040 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, EX1-26DEL
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010837" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010837" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010837</a>
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</span>
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<div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#26" class="mim-tip-reference" title="Casarino, L., Pecorara, M., Mori, P. G., Morfini, M., Mancuso, G., Scrivano, L., Molinari, A. C., Lanza, T., Giavarella, G., Loi, A., Perseu, L., Cao, A., Pirastu, M. <strong>Molecular basis of hemophilia A in Italians. (Abstract)</strong> Ric. Clin. Lab. 16: 227 only, 1986."None>Casarino et al. (1986)</a> found a 178+ kb deletion that removed exons 1 to 26.</p><p>In a patient with severe hemophilia A (patient H1) and factor VIII inhibitors, <a href="#27" class="mim-tip-reference" title="Casula, L., Murru, S., Pecorara, M., Ristaldi, M. S., Restagno, G., Mancuso, G., Morfini, M., De Biasi, R., Baudo, F., Carbonara, A., Mori, P. G., Cao, A., Pirastu, M. <strong>Recurrent mutations and three novel rearrangements in the factor VIII gene of hemophilia A patients of Italian descent.</strong> Blood 75: 662-670, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2105106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2105106</a>]" pmid="2105106">Casula et al. (1990)</a> found a total deletion of the factor VIII gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2105106" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div>
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<a id="0041" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0041 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, ARG372CYS
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852364 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852364;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852364" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852364" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010838" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010838" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010838</a>
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<p>This change was found in a case of moderately severe hemophilia A (<a href="/entry/306700">306700</a>) by <a href="#122" class="mim-tip-reference" title="Shima, M., Ware, J., Yoshioka, A., Fukui, H., Fulcher, C. A. <strong>An arginine to cysteine amino acid substitution at a critical thrombin cleavage site in a dysfunctional factor VIII molecule.</strong> Blood 74: 1612-1617, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2506948/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2506948</a>]" pmid="2506948">Shima et al. (1989)</a>. The mutation is in the thrombin cleavage activator site. <a href="#100" class="mim-tip-reference" title="O'Brien, D. P., Pattinson, J. K., Tuddenham, E. G. D. <strong>Purification and characterization of factor VIII 372-cys: a hypofunctional cofactor from a patient with moderately severe hemophilia A.</strong> Blood 75: 1664-1672, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2109644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2109644</a>]" pmid="2109644">O'Brien et al. (1990)</a> studied the relationship between structure and dysfunction. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2109644+2506948" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0042" class="mim-anchor"></a>
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<strong>.0042 HEMOPHILIA A</strong>
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F8, ARG2307GLN
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852360 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852360;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852360" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852360" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010839 OR RCV000851861 OR RCV001169905" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010839, RCV000851861, RCV001169905" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010839...</a>
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</span>
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<p><a href="#45" class="mim-tip-reference" title="Gitschier, J., Wood, W. I., Shuman, M. A., Lawn, R. M. <strong>Identification of a missense mutation in the factor VIII gene of a mild hemophiliac.</strong> Science 232: 1415-1416, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3012775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3012775</a>] [<a href="https://doi.org/10.1126/science.3012775" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3012775">Gitschier et al. (1986)</a> found this mutation in a case of mild hemophilia A (<a href="/entry/306700">306700</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3012775" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0043" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0043 HEMOPHILIA A</strong>
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</h4>
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F8, LEU2166SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852365 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852365;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852365" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852365" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010840" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010840" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010840</a>
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</span>
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<p><a href="#78" class="mim-tip-reference" title="Levinson, B., Lehesjoki, A.-E., de la Chapelle, A., Gitschier, J. <strong>Molecular analysis of hemophilia A mutations in the Finnish population.</strong> Am. J. Hum. Genet. 46: 53-62, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2104741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2104741</a>]" pmid="2104741">Levinson et al. (1990)</a> found this mutation in a patient with less than 1% factor VIII activity and clinically severe hemophilia A (<a href="/entry/306700">306700</a>). The substitution was caused by a T-to-C transition at position 6555 in exon 23. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2104741" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0044" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0044 HEMOPHILIA A</strong>
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</h4>
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<div style="float: left;">
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F8, ARG2116PRO
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852366 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852366;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852366?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852366" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852366" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010841" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010841" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010841</a>
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</span>
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<p><a href="#76" class="mim-tip-reference" title="Levinson, B., Janco, R., Phillips, J., III, Gitschier, J. <strong>A novel missense mutation in the factor VIII gene identified by analysis of amplified hemophilia DNA sequences.</strong> Nucleic Acids Res. 15: 9797-9805, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3122181/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3122181</a>] [<a href="https://doi.org/10.1093/nar/15.23.9797" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3122181">Levinson et al. (1987)</a> found this mutation in a severe case of hemophilia A (<a href="/entry/306700">306700</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3122181" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0045" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0045 HEMOPHILIA A</strong>
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</h4>
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F8, SER170LEU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852367 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852367;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852367" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852367" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010842 OR RCV003480026" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010842, RCV003480026" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010842...</a>
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</span>
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<p><a href="#28" class="mim-tip-reference" title="Chan, V., Chan, T. K., Tong, T. M., Todd, D. <strong>A novel missense mutation in exon 4 of the factor VIII:C gene resulting in moderately severe hemophilia A.</strong> Blood 74: 2688-2691, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2510835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2510835</a>]" pmid="2510835">Chan et al. (1989)</a> found this mutation in a moderately severe case of hemophilia A (<a href="/entry/306700">306700</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2510835" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0046" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0046 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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F8, EX15-18DEL
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010843" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010843" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010843</a>
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</span>
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#13" class="mim-tip-reference" title="Bardoni, B., Sampietro, M., Romano, M., Crapanzano, M., Mannucci, P. M., Camerino, G. <strong>Characterization of a partial deletion of the factor VIII gene in a haemophiliac with inhibitor.</strong> Hum. Genet. 79: 86-88, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2835307/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2835307</a>] [<a href="https://doi.org/10.1007/BF00291718" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2835307">Bardoni et al. (1988)</a> found deletion of exons 15 to 18. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2835307" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0047" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0047 HEMOPHILIA A</strong>
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</h4>
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F8, EX14DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010844" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010844" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010844</a>
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) with inhibitors, <a href="#57" class="mim-tip-reference" title="Higuchi, M., Kochhan, L., Schwaab, R., Egli, H., Brackmann, H. H., Horst, J., Olek, K. <strong>Molecular defects in hemophilia A: identification and characterization of mutations in the factor VIII gene and family analysis.</strong> Blood 74: 1045-1051, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2473810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2473810</a>]" pmid="2473810">Higuchi et al. (1989)</a> found deletion of exon 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2473810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0048" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0048 HEMOPHILIA A</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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F8, EX23-25DEL
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010845" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010845" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010845</a>
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</span>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#47" class="mim-tip-reference" title="Gitschier, J. <strong>Maternal duplication associated with gene deletion in sporadic hemophilia.</strong> Am. J. Hum. Genet. 43: 274-279, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2901224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2901224</a>]" pmid="2901224">Gitschier (1988)</a> found deletion of exons 23 to 25 as a result of a complex rearrangement with deletion-duplication. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2901224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<br />
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<a id="0049" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0049 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, EX14DEL
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010846" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010846" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010846</a>
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</span>
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</div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) accompanied by inhibitors, <a href="#86" class="mim-tip-reference" title="Mikami, S. <strong>Gene analysis in haemophilia A--restriction fragment length polymorphism and molecular defects in the factor VIII gene.</strong> Acta Haemat. Jpn. 51: 1680-1688, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2907841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2907841</a>]" pmid="2907841">Mikami (1988)</a> found deletion of exon 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2907841" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0050" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0050 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, EX7-9DEL
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010847" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010847" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010847</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) with inhibitors, <a href="#57" class="mim-tip-reference" title="Higuchi, M., Kochhan, L., Schwaab, R., Egli, H., Brackmann, H. H., Horst, J., Olek, K. <strong>Molecular defects in hemophilia A: identification and characterization of mutations in the factor VIII gene and family analysis.</strong> Blood 74: 1045-1051, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2473810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2473810</a>]" pmid="2473810">Higuchi et al. (1989)</a> found deletion of exons 7 to 9. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2473810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0051" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0051 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, EX5DEL
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010848" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010848" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010848</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#78" class="mim-tip-reference" title="Levinson, B., Lehesjoki, A.-E., de la Chapelle, A., Gitschier, J. <strong>Molecular analysis of hemophilia A mutations in the Finnish population.</strong> Am. J. Hum. Genet. 46: 53-62, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2104741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2104741</a>]" pmid="2104741">Levinson et al. (1990)</a> found a 3- to 6-kb deletion removing exon 5. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2104741" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0052" class="mim-anchor"></a>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0052 HEMOPHILIA A</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
|
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F8, EX5DEL
|
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</div>
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</span>
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<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010849" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010849" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010849</a>
|
|
</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#78" class="mim-tip-reference" title="Levinson, B., Lehesjoki, A.-E., de la Chapelle, A., Gitschier, J. <strong>Molecular analysis of hemophilia A mutations in the Finnish population.</strong> Am. J. Hum. Genet. 46: 53-62, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2104741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2104741</a>]" pmid="2104741">Levinson et al. (1990)</a> found a deletion of about 10 kb removing exon 5. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2104741" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<a id="0053" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0053 HEMOPHILIA A</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
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|
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<div style="float: left;">
|
|
F8, EX5DEL
|
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</div>
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</span>
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|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010850" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010850" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010850</a>
|
|
</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#22" class="mim-tip-reference" title="Briet, E., Bakker, B., Brocker-Vriends, A. <strong>Somatic and germinal mosaicism for a deletion in the factor VIII gene. (Abstract)</strong> Brit. J. Haemat. 71 (suppl. 1): 1 only, 1989."None>Briet et al. (1989)</a> found a deletion of about 2 kb removing exon 5. Somatic and gonadal mosaicism was demonstrated in the mother.</p>
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|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<a id="0054" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0054 HEMOPHILIA A</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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<div style="float: left;">
|
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F8, EX5-6 DEL
|
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</div>
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</span>
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<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010851" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010851" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010851</a>
|
|
</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) with inhibitors, <a href="#78" class="mim-tip-reference" title="Levinson, B., Lehesjoki, A.-E., de la Chapelle, A., Gitschier, J. <strong>Molecular analysis of hemophilia A mutations in the Finnish population.</strong> Am. J. Hum. Genet. 46: 53-62, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2104741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2104741</a>]" pmid="2104741">Levinson et al. (1990)</a> found a deletion of 3-10 kb removing exons 5 and 6. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2104741" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0055" class="mim-anchor"></a>
|
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<h4>
|
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<span class="mim-font">
|
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<strong>.0055 HEMOPHILIA A</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, ARG336TER
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852368 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852368;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852368?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852368" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852368" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010852" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010852" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010852</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#45" class="mim-tip-reference" title="Gitschier, J., Wood, W. I., Shuman, M. A., Lawn, R. M. <strong>Identification of a missense mutation in the factor VIII gene of a mild hemophiliac.</strong> Science 232: 1415-1416, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3012775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3012775</a>] [<a href="https://doi.org/10.1126/science.3012775" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3012775">Gitschier et al. (1986)</a> found this mutation in a patient with severe hemophilia A (<a href="/entry/306700">306700</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3012775" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<a id="0056" class="mim-anchor"></a>
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<strong>.0056 REMOVED FROM DATABASE</strong>
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<strong>.0057 HEMOPHILIA A</strong>
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F8, ASN1922ASP
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852369 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852369;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852369" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852369" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010853" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010853" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010853</a>
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</span>
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<p><a href="#128" class="mim-tip-reference" title="Traystman, M. D., Higuchi, M., Kasper, C. K., Antonarakis, S. E., Kazazian, H. H., Jr. <strong>Use of denaturing gradient gel electrophoresis to detect point mutations in the factor VIII gene.</strong> Genomics 6: 293-301, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2106480/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2106480</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90569-g" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2106480">Traystman et al. (1990)</a> demonstrated this mutation in patients with hemophilia A (<a href="/entry/306700">306700</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2106480" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0058" class="mim-anchor"></a>
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<strong>.0058 HEMOPHILIA A</strong>
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</h4>
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F8, CYS329ARG
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906430 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906430;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906430" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906430" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010854" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010854" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010854</a>
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</span>
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<div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#71" class="mim-tip-reference" title="Kogan, S., Gitschier, J. <strong>Mutations and a polymorphism in the factor VIII gene discovered by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 87: 2092-2096, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2107542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2107542</a>] [<a href="https://doi.org/10.1073/pnas.87.6.2092" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2107542">Kogan and Gitschier (1990)</a> demonstrated a thymine-to-cytosine mutation that changed the cysteine at codon 329 to an arginine. They used denaturing gel electrophoresis for this purpose. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2107542" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0059" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0059 HEMOPHILIA A</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, VAL326LEU
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852371 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852371;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852371" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852371" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010855" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010855" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010855</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#71" class="mim-tip-reference" title="Kogan, S., Gitschier, J. <strong>Mutations and a polymorphism in the factor VIII gene discovered by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 87: 2092-2096, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2107542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2107542</a>] [<a href="https://doi.org/10.1073/pnas.87.6.2092" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2107542">Kogan and Gitschier (1990)</a> demonstrated a guanine-to-cytosine change within codon 326 resulting in a valine-to-leucine change. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2107542" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#58" class="mim-tip-reference" title="Higuchi, M., Wong, C., Kochhan, L., Olek, K., Aronis, S., Kasper, C. K., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>Characterization of mutations in the factor VIII gene by direct sequencing of amplified genomic DNA.</strong> Genomics 6: 65-71, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2105906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2105906</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90448-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2105906">Higuchi et al. (1990)</a> found the same mutation in a patient with severe hemophilia A (JH30). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2105906" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div>
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<a id="0060" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0060 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, 4-BP DEL, FS
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906431 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906431;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906431" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906431" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010856" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010856" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010856</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>By means of denaturing gradient gel electrophoresis, <a href="#71" class="mim-tip-reference" title="Kogan, S., Gitschier, J. <strong>Mutations and a polymorphism in the factor VIII gene discovered by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 87: 2092-2096, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2107542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2107542</a>] [<a href="https://doi.org/10.1073/pnas.87.6.2092" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2107542">Kogan and Gitschier (1990)</a> demonstrated a deletion of 4 nucleotides within the region coding for the first acidic domain. The mutation caused a frameshift and a truncated protein product. The deletion occurred in a repetitive AAT and AAG motif. Small deletions in repeat sequences are thought to occur by a 'slipped mispairing' mechanism during DNA replication. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2107542" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div>
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<div>
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<a id="0061" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0061 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, EX13DUP
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010857" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010857" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010857</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with mild hemophilia A (<a href="/entry/306700">306700</a>), <a href="#90" class="mim-tip-reference" title="Murru, S., Casula, L., Pecorara, M., Mori, P., Cao, A., Pirastu, M. <strong>Illegitimate recombination produced a duplication within the FVIII gene in a patient with mild hemophilia A.</strong> Genomics 7: 115-118, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2159433/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2159433</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90526-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2159433">Murru et al. (1990)</a> characterized a duplication in exon 13. The duplication was the result of nonhomologous breakage and reunion of 2 misaligned wildtype chromosomes. Sequence analysis of the breakpoint region showed AT-rich sequences and possible topoisomerase I sites, whose involvement in cases of illegitimate recombination has been postulated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2159433" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div>
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<div>
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<a id="0062" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0062 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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F8, ARG427TER
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852372 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852372;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852372" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852372" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010858 OR RCV002247316" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010858, RCV002247316" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010858...</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#17" class="mim-tip-reference" title="Berg, L.-P., Wieland, K., Millar, D. S., Schlosser, M., Wagner, M., Kakkar, V. V., Reiss, J., Cooper, D. N. <strong>Detection of a novel point mutation causing haemophilia A by PCR/direct sequencing of ectopically-transcribed factor VIII mRNA.</strong> Hum. Genet. 85: 655-658, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2121641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2121641</a>] [<a href="https://doi.org/10.1007/BF00193593" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2121641">Berg et al. (1990)</a> took advantage of the fact that extremely low background levels of correctly spliced mRNA transcripts of tissue-specific genes can be demonstrated in a number of supposedly nonexpressing' cell types. This 'ectopic' or 'illegitimate' transcription was used to demonstrate the diagnostic utility of such transcripts in the construction of specific cDNAs derived from readily accessible 'nonexpressing' tissue, e.g., lymphocytes in the case of hemophilia A. Using PCR and direct sequencing, they demonstrated a novel mutation: a CGA-to-TGA transition at arginine 427. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2121641" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0063 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852373 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852373;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852373" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852373" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010859" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010859" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010859</a>
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<p>In a patient with sporadic severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#106" class="mim-tip-reference" title="Paynton, C., Sarkar, G., Sommer, S. S. <strong>Identification of mutations in two families with sporadic hemophilia A.</strong> Hum. Genet. 87: 397-400, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908817/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908817</a>] [<a href="https://doi.org/10.1007/BF00197155" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908817">Paynton et al. (1991)</a> identified a G-to-A transition resulting in substitution of lysine for glutamate-1704 (E1704K). The origin of the mutation was shown to be in the maternal grandfather who was 27 years old when his daughter was conceived. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1908817" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0064 HEMOPHILIA A</strong>
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F8, PRO2300SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852374 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852374;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852374?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852374" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852374" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010860 OR RCV004700214" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010860, RCV004700214" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010860...</a>
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<p>In a sporadic case of mild hemophilia A (<a href="/entry/306700">306700</a>), <a href="#106" class="mim-tip-reference" title="Paynton, C., Sarkar, G., Sommer, S. S. <strong>Identification of mutations in two families with sporadic hemophilia A.</strong> Hum. Genet. 87: 397-400, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908817/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908817</a>] [<a href="https://doi.org/10.1007/BF00197155" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908817">Paynton et al. (1991)</a> demonstrated a C-to-T transition that resulted in mutation of serine for proline-2300. <a href="#106" class="mim-tip-reference" title="Paynton, C., Sarkar, G., Sommer, S. S. <strong>Identification of mutations in two families with sporadic hemophilia A.</strong> Hum. Genet. 87: 397-400, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908817/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908817</a>] [<a href="https://doi.org/10.1007/BF00197155" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908817">Paynton et al. (1991)</a> used PCR amplification of specific alleles (PASA) to screen 96 unrelated hemophiliacs for the P2300S mutation; none of these patients had the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1908817" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0065 HEMOPHILIA A</strong>
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F8, MET1772THR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852375 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852375;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852375" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852375" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010861" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010861" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010861</a>
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<p>In a study of the molecular defects responsible for crossreacting material-positive hemophilia A (<a href="/entry/306700">306700</a>), <a href="#3" class="mim-tip-reference" title="Aly, A. M., Arai, M., Hoyer, L. W. <strong>Cysteamine enhances the procoagulant activity of factor VIII-East Hartford, a dysfunctional protein due to a light chain thrombin cleavage site mutation (arginine-1689 to cysteine).</strong> J. Clin. Invest. 89: 1375-1381, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1569180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1569180</a>] [<a href="https://doi.org/10.1172/JCI115725" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1569180">Aly et al. (1992)</a> found 2 patients in whom the nonfunctional factor VIII-like protein had abnormal, slower-moving heavy or light chains on SDS/PAGE. Both patients had severe hemophilia A with less than 1% of normal factor VIII activity but with normal plasma level of factor VIII antigen. By denaturing gradient gel electrophoresis screening of PCR-amplified products of the factor VIII coding DNA sequence, followed by nucleotide sequencing of the abnormal PCR products, they identified in 1 patient a met1772-to-thr mutation that created a potential new N-glycosylation site at asparagine-1770 in the factor VIII light chain. In the second patient, an isoleucine-to-threonine substitution at position 566 created a potential new N-glycosylation site at asparagine-564 in the A2 domain of the factor VIII heavy chain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1569180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Abnormal N-glycosylation, blocking factor VIII probe procoagulant activity, represented a previously unrecognized mechanism for the pathogenesis of severe hemophilia A.</p>
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<strong>.0066 HEMOPHILIA A</strong>
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F8, ILE566THR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852376 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852376;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852376" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852376" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010862" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010862" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010862</a>
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<p>See <a href="#0065">300841.0065</a>.</p>
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<strong>.0067 HEMOPHILIA A, SEVERE</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010863" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010863" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010863</a>
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<p><a href="#73" class="mim-tip-reference" title="Lakich, D., Kazazian, H. H., Jr., Antonarakis, S. E., Gitschier, J. <strong>Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A.</strong> Nature Genet. 5: 236-241, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8275087/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8275087</a>] [<a href="https://doi.org/10.1038/ng1193-236" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8275087">Lakich et al. (1993)</a> concluded that many mutations in the F8C gene result from recombination between homologous sequences within intron 22 of the F8C gene and those upstream of the gene. Such a recombination would lead to an inversion of all intervening DNA and a disruption of the gene. Among 23 patients with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#97" class="mim-tip-reference" title="Naylor, J. A., Green, P. M., Rizza, C. R., Giannelli, F. <strong>Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients.</strong> Hum. Molec. Genet. 2: 11-17, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490618</a>] [<a href="https://doi.org/10.1093/hmg/2.1.11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490618">Naylor et al. (1993)</a> found that approximately 40% were on the basis of this mutation involving intron 22. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8490618+8275087" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>It is hypothesized that the inversion mutations occur almost exclusively in germ cells during meiotic cell division by an intrachromosomal recombination between a 9.6-kb sequence within intron 22 and 1 of 2 almost identical copies located about 300 kb distal to the factor VIII gene at the telomeric end of the X chromosome. Most inversion mutations originate in male germ cells, where the lack of bivalent formation may facilitate flipping of the telomeric end of the single X chromosome. <a href="#102" class="mim-tip-reference" title="Oldenburg, J., Rost, S., El-Maarri, O., Leuer, M., Olek, K., Muller, C. R., Schwaab, R. <strong>De novo factor VIII gene intron 22 inversion in a female carrier presents as a somatic mosaicism.</strong> Blood 96: 2905-2906, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11023529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11023529</a>]" pmid="11023529">Oldenburg et al. (2000)</a> reported the first instance of intron 22 inversion presenting as somatic mosaicism in a female, affecting only about 50% of lymphocyte and fibroblast cells of the proposita. Supposing a postzygotic de novo mutation as the usual cause of somatic mosaicism, the finding implies that the intron 22 inversion mutation is not restricted to meiotic cell divisions but can also occur during mitotic cell divisions, either in germ cell precursors or in somatic cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11023529" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#81" class="mim-tip-reference" title="Lozier, J. N., Dutra, A., Pak, E., Zhou, N., Zheng, Z., Nichols, T. C., Bellinger, D. A., Read, M., Morgan, R. A. <strong>The Chapel Hill hemophilia A dog colony exhibits a factor VIII gene inversion.</strong> Proc. Nat. Acad. Sci. 99: 12991-12996, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12242334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12242334</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12242334[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.192219599" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12242334">Lozier et al. (2002)</a> found that the defect in the Chapel Hill hemophilia A dog colony started by <a href="#24" class="mim-tip-reference" title="Brinkhous, K. M., Graham, J. B. <strong>Hemophilia in the female dog.</strong> Science 111: 723-724, 1950.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15431070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15431070</a>] [<a href="https://doi.org/10.1126/science.111.2896.723" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15431070">Brinkhous and Graham (1950)</a> replicates the F8 gene inversion commonly seen in humans with severe hemophilia A. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15431070+12242334" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010896 OR RCV003934820" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010896, RCV003934820" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010896...</a>
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<p><a href="#19" class="mim-tip-reference" title="Bidichandani, S. I., Shiach, C. R., Lanyon, W. G., Connor, J. M. <strong>A novel splice donor mutation affecting position +3 in intron 6 of the factor VIII gene.</strong> Hum. Molec. Genet. 3: 651-653, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8069313/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8069313</a>] [<a href="https://doi.org/10.1093/hmg/3.4.651" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8069313">Bidichandani et al. (1994)</a> studied 15 randomly selected hemophilia A (<a href="/entry/306700">306700</a>) patients, 9 of whom were severely affected. They reported a new mutation affecting the intron 6 splice donor site in the factor VIII gene of 2 patients, that corresponds to an exon skipping event involving exon 5 and 6. The mutation is an A-to-G substitution at position +3 in the splice donor site of intron 6 in both the patients. This exon skipping event left the translational frame intact, and the resultant in-frame deletion of 186-bp in the mature mRNA is predicted to cause a shortening of the mature factor VIII polypeptide by 62 amino acid residues. Direct sequencing showed that exon 5 is consistently skipped along with exon 6 in the mature factor VIII mRNA. Both patients have a disease of moderate severity and residual factor VIII activity 3% of the normal. <a href="#19" class="mim-tip-reference" title="Bidichandani, S. I., Shiach, C. R., Lanyon, W. G., Connor, J. M. <strong>A novel splice donor mutation affecting position +3 in intron 6 of the factor VIII gene.</strong> Hum. Molec. Genet. 3: 651-653, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8069313/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8069313</a>] [<a href="https://doi.org/10.1093/hmg/3.4.651" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8069313">Bidichandani et al. (1994)</a> noted that a patient lacking exon 5 and 6 in the mature factor VIII mRNA due to gross DNA deletion has previously been reported to have severe hemophilia A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8069313" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0069 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906432 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906432;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906432" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906432" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010865 OR RCV003114181" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010865, RCV003114181" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010865...</a>
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<p>In 2 patients with hemophilia A (<a href="/entry/306700">306700</a>), <a href="#105" class="mim-tip-reference" title="Pattinson, J. K., Millar, D. S., McVey, J. H., Grundy, C. B., Wieland, K., Mibashan, R. S., Martinowitz, U., Tan-Un, K., Vidaud, M., Goossens, M., Sampietro, M., Mannucci, P. M., and 17 others. <strong>The molecular genetic analysis of hemophilia A: a directed search strategy for the detection of point mutations in the human factor VIII gene.</strong> Blood 76: 2242-2248, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1979502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1979502</a>]" pmid="1979502">Pattinson et al. (1990)</a> identified mutation of CGA to TGA at codon -5 in exon 1, resulting in a stop codon. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. This mutation has also been found by others (<a href="#114" class="mim-tip-reference" title="Reiner, A. P., Thompson, A. R. <strong>Screening for nonsense mutations in patients with severe hemophilia A can provide rapid, direct carrier detection.</strong> Hum. Genet. 89: 88-94, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1349567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1349567</a>] [<a href="https://doi.org/10.1007/BF00207049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1349567">Reiner and Thompson, 1992</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1349567+1979502" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852377 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852377;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852377" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852377" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010866" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010866" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010866</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a CTG-to-CGG transversion at codon 7 in exon 1 of the A1 domain, resulting in arginine for leucine-7. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0071 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852378 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852378;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852378" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852378" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010867" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010867" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010867</a>
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<p><a href="#33" class="mim-tip-reference" title="Diamond, C., Kogan, S., Levinson, B., Gitschier, J. <strong>Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A.</strong> Hum. Mutat. 1: 248-257, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301932</a>] [<a href="https://doi.org/10.1002/humu.1380010312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301932">Diamond et al. (1992)</a> found this mutation in a patient with mild hemophilia A (<a href="/entry/306700">306700</a>). The substitution is caused by a GAA-to-GTA transversion at codon 11 in exon 1, resulting in valine for glutamic acid-11. This mutation is found in the A1 domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0072 HEMOPHILIA A</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010868" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010868" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010868</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported in a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) the deletion of 89 nucleotides from codon 14 to 29 in exon 1, resulting in a frameshift. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0073" class="mim-anchor"></a>
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<h4>
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<strong>.0073 HEMOPHILIA A</strong>
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F8, GLY22CYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852379 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852379;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852379?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852379" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852379" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010869 OR RCV002247317" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010869, RCV002247317" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010869...</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this substitution in 2 patients with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a GGT-to-TGT transversion at codon 22 in exon 1 of the A1 domain, resulting in cysteine for glycine-22. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0074" class="mim-anchor"></a>
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<strong>.0074 HEMOPHILIA A</strong>
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<span class="mim-text-font">
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F8, 10-BP INS, FS
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2124149047 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2124149047;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2124149047" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2124149047" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010870" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010870" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010870</a>
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> identified the insertion of 10 nucleotides (TTCCATTCAA) resulting in a frameshift downstream from codon 38 in exon 2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0075" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0075 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, 2-BP DEL, FS
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906433 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906433;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906433" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906433" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010871" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010871" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010871</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> identified the deletion of 2 nucleotides (AA) resulting in a frameshift downstream from codon 48 in exon 2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0076" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0076 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, 4-BP DEL, FS
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs387906434 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906434;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs387906434?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906434" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906434" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010872 OR RCV004791212" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010872, RCV004791212" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010872...</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported in a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) the deletion of 4 nucleotides (GTTT) resulting in a frameshift downstream from codon 50 in exon 2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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<div>
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<div>
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<a id="0077" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0077 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, 2-BP DEL, FS
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906435 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906435;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906435" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906435" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010873" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010873" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010873</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported the deletion of 2 nucleotides (GT) resulting in a frameshift downstream from codon 102 or 3 in exon 3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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<div>
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</div>
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<div>
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<a id="0078" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0078 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, 23-BP DEL, FS
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010874" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010874" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010874</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a> identified in a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) the deletion of 23 nucleotides resulting in a frameshift downstream from codon 104 in exon 3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1908096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0079" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0079 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, IVS4AS, A-G, -2
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2124134457 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2124134457;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2124134457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2124134457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010875" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010875" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010875</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported the substitution of A to G at the second nucleotide of the acceptor splice site of intron 4, resulting in abnormal splicing. The patient had 1.7% factor VIII activity, 1.3% factor VIII antigen, and a severe hemophilia A (<a href="/entry/306700">306700</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0080" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0080 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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F8, GLY70ASP
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852380 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852380;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852380" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852380" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010876" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010876" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010876</a>
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</span>
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<span class="mim-text-font">
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this gly70-to-asp mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a GGT-to-GAT transition at codon 70 in exon 3 of the A1 domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0081" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0081 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, GLY73VAL
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852381 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852381;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852381" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852381" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010877" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010877" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010877</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#33" class="mim-tip-reference" title="Diamond, C., Kogan, S., Levinson, B., Gitschier, J. <strong>Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A.</strong> Hum. Mutat. 1: 248-257, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301932</a>] [<a href="https://doi.org/10.1002/humu.1380010312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301932">Diamond et al. (1992)</a> found this mutation in a patient with mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a GGT-to-GTT transversion at codon 73 in exon 3 of the A1 domain, resulting in valine for glycine-73. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0082" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0082 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, VAL80ASP
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852382 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852382;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852382" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852382" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010878" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010878" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010878</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this val80-to-asp mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a GTT-to-GAT transversion at codon 80 in exon 3 of the A1 domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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<div>
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</div>
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</div>
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<div>
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<div>
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<a id="0083" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0083 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, VAL85ASP
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852383 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852383;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852383" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852383" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010879" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010879" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010879</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#33" class="mim-tip-reference" title="Diamond, C., Kogan, S., Levinson, B., Gitschier, J. <strong>Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A.</strong> Hum. Mutat. 1: 248-257, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301932</a>] [<a href="https://doi.org/10.1002/humu.1380010312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301932">Diamond et al. (1992)</a> found this val85-to-asp mutation in a patient with mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a GTC-to-GAC transversion at codon 85 in exon 3 of the A1 domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<a id="0084" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0084 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, LYS89THR
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852384 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852384;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852384" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852384" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010880 OR RCV000508582 OR RCV002247318" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010880, RCV000508582, RCV002247318" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010880...</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a> found this lys89-to-thr mutation in a patient with mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by an AAG-to-ACG transversion at codon 89 in exon 3 of the A1 domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1908096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0085" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0085 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, MET91VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852385 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852385;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852385" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852385" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010881" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010881" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010881</a>
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<p><a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a> found this mutation in a patient with moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by an ATG-to-GTG transition at codon 91 in exon 3 of the A1 domain, resulting in valine for methionine-91. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1908096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0086 HEMOPHILIA A</strong>
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F8, LEU98ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852386 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852386;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852386" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852386" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010882" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010882" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010882</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). It is caused by a CTT-to-CGT transversion at codon 98 in exon 3 of the A1 domain, resulting in arginine for leucine-98. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0087 HEMOPHILIA A</strong>
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F8, GLY130ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852387 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852387;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852387" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852387" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010883" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010883" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010883</a>
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<span class="mim-text-font">
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<p>In a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> identified a GGA-to-CGA transversion at codon 111 in exon 3 of the A1 domain of the F8 gene, resulting in arginine for glycine-111. Including the 19-amino acid signal peptide of the F8 gene (<a href="#132" class="mim-tip-reference" title="Vehar, G. A., Keyt, B., Eaton, D., Rodriguez, H., O'Brien, D. P., Rotblat, F., Oppermann, H., Keck, R., Wood, W. I., Harkins, R. N., Tuddenham, E. G. D., Lawn, R. M., Capon, D. J. <strong>Structure of human factor VIII.</strong> Nature 312: 337-342, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438527</a>] [<a href="https://doi.org/10.1038/312337a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438527">Vehar et al., 1984</a>), the mutation is designated gly130-to-arg (G130R). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6438527+8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0088" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0088 HEMOPHILIA A</strong>
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F8, GLU132ASP
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852388 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852388;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852388?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852388" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852388" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010884 OR RCV001529373 OR RCV002247319 OR RCV002280860 OR RCV002496321 OR RCV003952352" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010884, RCV001529373, RCV002247319, RCV002280860, RCV002496321, RCV003952352" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010884...</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported a glu113-to-asp mutation in a patient with less than 1% factor VIII activity, severe hemophilia A (<a href="/entry/306700">306700</a>) and inhibitors. It is caused by a GAA-to-GAC transversion at codon 113 in exon 4 of the A1 domain of factor VIII. Including the 19-amino acid signal peptide of the F8 gene (<a href="#132" class="mim-tip-reference" title="Vehar, G. A., Keyt, B., Eaton, D., Rodriguez, H., O'Brien, D. P., Rotblat, F., Oppermann, H., Keck, R., Wood, W. I., Harkins, R. N., Tuddenham, E. G. D., Lawn, R. M., Capon, D. J. <strong>Structure of human factor VIII.</strong> Nature 312: 337-342, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438527</a>] [<a href="https://doi.org/10.1038/312337a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438527">Vehar et al., 1984</a>), this mutation is designated glu132-to-asp (E132D). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6438527+7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0089" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0089 HEMOPHILIA A</strong>
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</h4>
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F8, TYR114CYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852389 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852389;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852389" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852389" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010885" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010885" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010885</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this tyr114-to-cys mutation in a patient with 6.3% factor VIII activity, 10.7% factor VIII antigen, and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a TAT-to-TGT transition at codon 114 in exon 4. This mutation is found in the A1 domain of factor VIII. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0090" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0090 HEMOPHILIA A</strong>
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</h4>
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F8, ASP116GLY
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852390 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852390;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852390" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852390" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010886" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010886" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010886</a>
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<span class="mim-text-font">
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a GAT-to-GGT transition at codon 116 in exon 4 of the A1 domain, resulting in glycine for aspartic acid-116. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0091 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852391 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852391;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852391" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852391" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010887 OR RCV004799739" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010887, RCV004799739" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010887...</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with 2% factor VIII activity, 10.7% factor VIII antigen, and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by an ACC-to-ATC transition at codon 118 in exon 4 of the A1 domain, resulting in isoleucine for threonine-118. Including the 19-amino acid signal peptide of the F8 gene (<a href="#132" class="mim-tip-reference" title="Vehar, G. A., Keyt, B., Eaton, D., Rodriguez, H., O'Brien, D. P., Rotblat, F., Oppermann, H., Keck, R., Wood, W. I., Harkins, R. N., Tuddenham, E. G. D., Lawn, R. M., Capon, D. J. <strong>Structure of human factor VIII.</strong> Nature 312: 337-342, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438527</a>] [<a href="https://doi.org/10.1038/312337a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438527">Vehar et al., 1984</a>), this mutation is designated thr137-to-ile (T137I). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6438527+7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0092 HEMOPHILIA A</strong>
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F8, GLY145VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852392 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852392;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852392?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852392" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852392" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010888" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010888" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010888</a>
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<p><a href="#33" class="mim-tip-reference" title="Diamond, C., Kogan, S., Levinson, B., Gitschier, J. <strong>Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A.</strong> Hum. Mutat. 1: 248-257, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301932</a>] [<a href="https://doi.org/10.1002/humu.1380010312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301932">Diamond et al. (1992)</a> found this gly145-to-val mutation in a patient with mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a GGT-to-GTT transversion at codon 145 in exon 4 of the A1 domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0093" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0093 HEMOPHILIA A</strong>
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F8, PRO146SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852393 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852393;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852393?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852393" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852393" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010889 OR RCV003657257" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010889, RCV003657257" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010889...</a>
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<p><a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> found a pro146-to-ser mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a CCA-to-TCA transition at codon 146 in exon 4 of the A1 domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0094 HEMOPHILIA A</strong>
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F8, VAL162MET
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852394 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852394;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852394" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852394" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010890 OR RCV000851946 OR RCV001701720 OR RCV003398478" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010890, RCV000851946, RCV001701720, RCV003398478" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010890...</a>
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<p><a href="#33" class="mim-tip-reference" title="Diamond, C., Kogan, S., Levinson, B., Gitschier, J. <strong>Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A.</strong> Hum. Mutat. 1: 248-257, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301932</a>] [<a href="https://doi.org/10.1002/humu.1380010312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301932">Diamond et al. (1992)</a> found this mutation in 5 patients with 3.5-8.5% factor VIII activity, 6-35.9% factor VIII antigen, and moderate to mild hemophilia A (<a href="/entry/306700">306700</a>). A GTG-to-ATG transition at codon 162 in exon 4 of the A1 domain resulted in a val162-to-met change. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0095 HEMOPHILIA A</strong>
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F8, LYS166THR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852395 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852395;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852395" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852395" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010891" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010891" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010891</a>
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<p><a href="#54" class="mim-tip-reference" title="Higuchi, M., Antonarakis, S. E., Kasch, L., Oldenburg, J., Economou-Petersen, E., Olek, K., Arai, M., Inaba, H., Kazazian, H. H., Jr. <strong>Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 88: 8307-8311, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1924291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1924291</a>] [<a href="https://doi.org/10.1073/pnas.88.19.8307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1924291">Higuchi et al. (1991)</a> found this lys166-to-thr mutation in a patient with 19% factor VIII activity and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by an AAA-to-ACA transversion at codon 166 in exon 4 of the A1 domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1924291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0096 HEMOPHILIA A</strong>
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F8, ASP203VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852396 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852396;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852396" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852396" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010892" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010892" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010892</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with 2% factor VIII activity, 8.5% factor VIII antigen, and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a GAT-to-GTT transversion at codon 203 in exon 5 of the A1 domain and resulted in valine for aspartic acid-203. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0097" class="mim-anchor"></a>
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<strong>.0097 HEMOPHILIA A</strong>
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</h4>
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F8, GLY205TRP
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852397 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852397;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852397" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852397" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010893" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010893" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010893</a>
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<p><a href="#54" class="mim-tip-reference" title="Higuchi, M., Antonarakis, S. E., Kasch, L., Oldenburg, J., Economou-Petersen, E., Olek, K., Arai, M., Inaba, H., Kazazian, H. H., Jr. <strong>Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 88: 8307-8311, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1924291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1924291</a>] [<a href="https://doi.org/10.1073/pnas.88.19.8307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1924291">Higuchi et al. (1991)</a> found this mutation in a patient with 3.2% factor VIII activity and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a GGG-to-TGG transversion at codon 205 in exon 5 of the A1 domain, resulting in tryptophan for glycine-205. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1924291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0098" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0098 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, 2-BP DEL, FS
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906436 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906436;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906436" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906436" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010894" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010894" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010894</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> identified the deletion of 2 nucleotides (AG) resulting in a frameshift downstream from codon 210-211 in exon 6. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0099" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0099 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, IVS5AS, A-G, -2
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2124131475 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2124131475;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2124131475" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2124131475" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010895" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010895" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010895</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#95" class="mim-tip-reference" title="Naylor, J. A., Green, P. M., Montandon, A. J., Rizza, C. R., Giannelli, F. <strong>Detection of three novel mutations in two haemophilia A patients by rapid screening of whole essential region of factor VIII gene.</strong> Lancet 337: 635-639, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1671991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1671991</a>] [<a href="https://doi.org/10.1016/0140-6736(91)92450-g" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1671991">Naylor et al. (1991)</a> identified an A-to-G transition at the second nucleotide of the acceptor splice site of intron 5, which resulted in abnormal splicing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1671991" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div>
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<a id="0100" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0100 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, IVS6DS, A-G, +3
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2073548872 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2073548872;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2073548872" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2073548872" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010896 OR RCV003934820" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010896, RCV003934820" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010896...</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with 3-4% factor VIII activity and moderate hemophilia A (<a href="/entry/306700">306700</a>), <a href="#19" class="mim-tip-reference" title="Bidichandani, S. I., Shiach, C. R., Lanyon, W. G., Connor, J. M. <strong>A novel splice donor mutation affecting position +3 in intron 6 of the factor VIII gene.</strong> Hum. Molec. Genet. 3: 651-653, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8069313/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8069313</a>] [<a href="https://doi.org/10.1093/hmg/3.4.651" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8069313">Bidichandani et al. (1994)</a> identified mutation of A to G at the third nucleotide of the donor splice site of intron 6, which resulted in abnormal splicing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8069313" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div>
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<a id="0101" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0101 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, IVS6AS, G-C, -1
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2073445259 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2073445259;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2073445259" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2073445259" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001265089" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001265089" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001265089</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>) who had a G-to-C transversion. The mutation was in the first nucleotide of the acceptor splice site of intron 6 and resulted in abnormal splicing ({Antonarakis and Kazazian, unpublished}). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div>
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<a id="0102" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0102 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, GLY266GLU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852398 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852398;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852398" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852398" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010898" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010898" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010898</a>
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<p><a href="#36" class="mim-tip-reference" title="Eckhardt, C. L., van Velzen, A. S., Peters, M., Astermark, J., Brons, P. P., Castaman, G., Cnossen, M. H., Dors, N., Escuriola-Ettingshausen, C., Hamulyak, K., Hart, D. P., Hay, C. R. M., and 33 others. <strong>Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A.</strong> Blood 122: 1954-1962, 2013. Note: Erratum: Blood 123: 3056 only, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23926300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23926300</a>] [<a href="https://doi.org/10.1182/blood-2013-02-483263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23926300">Eckhardt et al. (2013)</a> noted that a gly266-to-glu (G266E) mutation in the F8 gene (gly247-to-glu in the mature protein) had been found in patients with hemophilia A (<a href="/entry/306700">306700</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23926300" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> had reported this mutation as a gly247-to-gln substitution caused by a GGA-to-GAA transition at codon 247 in exon 7 of the A1 domain. The patient had less than 1% factor VIII activity and severe hemophilia A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0103" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0103 HEMOPHILIA A</strong>
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F8, TRP274TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs34371500 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs34371500;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs34371500" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs34371500" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010899" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010899" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010899</a>
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</span>
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<span class="mim-text-font">
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<p>In a patient with hemophilia A (<a href="/entry/306700">306700</a>), <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported mutation of TGG-to-TGA at codon 255 in exon 7, resulting in a stop codon. Including the 19-amino acid signal peptide of the F8 gene (<a href="#132" class="mim-tip-reference" title="Vehar, G. A., Keyt, B., Eaton, D., Rodriguez, H., O'Brien, D. P., Rotblat, F., Oppermann, H., Keck, R., Wood, W. I., Harkins, R. N., Tuddenham, E. G. D., Lawn, R. M., Capon, D. J. <strong>Structure of human factor VIII.</strong> Nature 312: 337-342, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438527</a>] [<a href="https://doi.org/10.1038/312337a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438527">Vehar et al., 1984</a>), this mutation is designated trp274-to-ter (W274X). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6438527+7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0104" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0104 HEMOPHILIA A</strong>
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</span>
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</h4>
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<div style="float: left;">
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F8, GLY278ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852399 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852399;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852399" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852399" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010900" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010900" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010900</a>
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</span>
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<span class="mim-text-font">
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a GGA-to-AGA transition at codon 259 in exon 7 of the A1 domain, resulting in arginine for glycine-259. Including the 19-amino acid signal peptide of the F8 gene (<a href="#132" class="mim-tip-reference" title="Vehar, G. A., Keyt, B., Eaton, D., Rodriguez, H., O'Brien, D. P., Rotblat, F., Oppermann, H., Keck, R., Wood, W. I., Harkins, R. N., Tuddenham, E. G. D., Lawn, R. M., Capon, D. J. <strong>Structure of human factor VIII.</strong> Nature 312: 337-342, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438527</a>] [<a href="https://doi.org/10.1038/312337a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438527">Vehar et al., 1984</a>), this mutation is designated gly6278-to-arg (G278R). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6438527+7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div>
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<div>
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<a id="0105" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0105 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, 1-BP DEL, FS
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906437 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906437;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906437" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906437" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010901" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010901" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010901</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported the deletion of 1 nucleotide (T) resulting in a frameshift downstream from codon 264 in exon 7. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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<a id="0106" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0106 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, VAL266GLY
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</div>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852400 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852400;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852400" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852400" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010902" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010902" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010902</a>
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</span>
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<span class="mim-text-font">
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<p><a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a> found this mutation in a patient with mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a GTG-to-GGG transversion at codon 266 in exon 7 of the A1 domain, resulting in glycine for valine-266. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1908096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0107" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0107 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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F8, THR275ILE
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852401 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852401;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852401" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852401" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010903" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010903" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010903</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with 4-4.8% factor VIII activity, 20-40% factor VIII antigen, and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a ACA-to-ATA transition at codon 275 in exon 7 of the A1 domain, resulting in isoleucine for threonine-275. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0108 HEMOPHILIA A</strong>
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F8, ASN280ILE
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852402 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852402;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852402" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852402" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010904" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010904" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010904</a>
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<p><a href="#108" class="mim-tip-reference" title="Pieneman, W. C., Reitsma, P. H., Briet, E. <strong>Double strand conformation polymorphism (DSCP) detects two point mutations at codon 280 (AAC-ATC) and at codon 431 (TAC-AAC) of the blood coagulation factor VIII gene.</strong> Thromb. Haemost. 69: 473-475, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8322269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8322269</a>]" pmid="8322269">Pieneman et al. (1993)</a> found this mutation in a patient with 8-12% factor VIII activity and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a AAC-to-ATC transversion at codon 280 in exon 7 of the A1 domain, resulting in isoleucine for asparagine-280. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8322269" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0109" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0109 HEMOPHILIA A</strong>
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F8, ARG282HIS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852403 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852403;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852403" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852403" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010905 OR RCV000255290 OR RCV004745151" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010905, RCV000255290, RCV004745151" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010905...</a>
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<p><a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a> found this mutation in a patient with less than 1% factor VIII activity, 18% factor VIII antigen, and severe hemophilia A (<a href="/entry/306700">306700</a>). A CGC-to-CAC transition at codon 282 in exon 7 of the A1 domain results in an arg282-to-his change. The G-to-A transition follows the rule of CG-to-CA mutations at CG dinucleotides. This mutation has also been found by others (<a href="#84" class="mim-tip-reference" title="McGinniss, M. J., Kazazian, H. H., Jr., Hoyer, L. W., Bi, L., Inaba, H., Antonarakis, S. E. <strong>Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A.</strong> Genomics 15: 392-398, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8449505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8449505</a>] [<a href="https://doi.org/10.1006/geno.1993.1073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8449505">McGinniss et al., 1993</a>; <a href="#97" class="mim-tip-reference" title="Naylor, J. A., Green, P. M., Rizza, C. R., Giannelli, F. <strong>Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients.</strong> Hum. Molec. Genet. 2: 11-17, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490618</a>] [<a href="https://doi.org/10.1093/hmg/2.1.11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490618">Naylor et al., 1993</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8449505+8490618+1908096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0110" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0110 HEMOPHILIA A</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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F8, ARG282LEU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852403 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852403;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852403" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852403" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010906" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010906" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010906</a>
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</span>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in 2 patients with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). It is caused by a CGC-to-CTC transversion at codon 282 in exon 7 of the A1 domain, resulting in leucine for arginine-282. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0111" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0111 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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F8, 1-BP DEL, FS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906438 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906438;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906438" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906438" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010907" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010907" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010907</a>
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported the deletion of 1 nucleotide (G), resulting in a frameshift downstream from codon 283 in exon 7. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0112" class="mim-anchor"></a>
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<strong>.0112 HEMOPHILIA A</strong>
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F8, SER289LEU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852404 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852404;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852404" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852404" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010908 OR RCV003415685" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010908, RCV003415685" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010908...</a>
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</span>
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<span class="mim-text-font">
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<p><a href="#84" class="mim-tip-reference" title="McGinniss, M. J., Kazazian, H. H., Jr., Hoyer, L. W., Bi, L., Inaba, H., Antonarakis, S. E. <strong>Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A.</strong> Genomics 15: 392-398, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8449505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8449505</a>] [<a href="https://doi.org/10.1006/geno.1993.1073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8449505">McGinniss et al. (1993)</a> found this substitution in a patient with 37% factor VIII activity, 106% factor VIII antigen and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a TCG-to-TTG transition at codon 289 in exon 7 of the A1 domain, resulting in leucine for serine-289. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8449505" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0113 HEMOPHILIA A</strong>
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F8, PHE293SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852405 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852405;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852405" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852405" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010909 OR RCV000852250 OR RCV003656098" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010909, RCV000852250, RCV003656098" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010909...</a>
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<p><a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a> found this mutation in 3 patients with 7-21.5% factor VIII activity, 2-17.9% factor VIII antigen, and mild hemophilia A (<a href="/entry/306700">306700</a>). An ACT-to-GCT transition at codon 295 in exon 7 of the A1 domain results in alanine for threonine-295. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1908096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0114 HEMOPHILIA A</strong>
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F8, THR314ALA
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852406 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852406;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852406?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852406" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852406" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010910 OR RCV004566717" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010910, RCV004566717" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010910...</a>
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<p><a href="#54" class="mim-tip-reference" title="Higuchi, M., Antonarakis, S. E., Kasch, L., Oldenburg, J., Economou-Petersen, E., Olek, K., Arai, M., Inaba, H., Kazazian, H. H., Jr. <strong>Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 88: 8307-8311, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1924291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1924291</a>] [<a href="https://doi.org/10.1073/pnas.88.19.8307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1924291">Higuchi et al. (1991)</a> found this mutation in 3 patients with 7-21.5% factor VIII activity, 2-17.9% factor VIII antigen, and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by an ACT-to-GCT transition at codon 295 in exon 7 of the A1 domain, resulting in alanine for threonine-295. Including the 19-amino acid signal peptide of the F8 gene (<a href="#132" class="mim-tip-reference" title="Vehar, G. A., Keyt, B., Eaton, D., Rodriguez, H., O'Brien, D. P., Rotblat, F., Oppermann, H., Keck, R., Wood, W. I., Harkins, R. N., Tuddenham, E. G. D., Lawn, R. M., Capon, D. J. <strong>Structure of human factor VIII.</strong> Nature 312: 337-342, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438527</a>] [<a href="https://doi.org/10.1038/312337a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438527">Vehar et al., 1984</a>), this mutation is designated thr314-to-ala (T314A). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6438527+1924291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0115" class="mim-anchor"></a>
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<strong>.0115 HEMOPHILIA A</strong>
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F8, 1-BP DEL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906439 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906439;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906439" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906439" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010911" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010911" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010911</a>
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<p>(<a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a>) reported in a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) the deletion of 1 nucleotide (G), resulting in a frameshift downstream from codon 296 in exon 7. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0116" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0116 HEMOPHILIA A</strong>
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F8, LEU308PRO
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852407 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852407;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852407" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852407" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010912" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010912" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010912</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a CTG-to-CCG transition at codon 308 in exon 7 of the A1 domain, resulting in proline for leucine-308. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0117 HEMOPHILIA A</strong>
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F8, TYR342TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852408 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852408;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852408" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852408" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010913" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010913" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010913</a>
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<p>In 1 patient with hemophilia A (<a href="/entry/306700">306700</a>), <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> identified a TAT-to-TAA substitution at codon 323 in exon 8, resulting in a stop codon. Including the 19-amino acid signal peptide of the F8 gene (<a href="#132" class="mim-tip-reference" title="Vehar, G. A., Keyt, B., Eaton, D., Rodriguez, H., O'Brien, D. P., Rotblat, F., Oppermann, H., Keck, R., Wood, W. I., Harkins, R. N., Tuddenham, E. G. D., Lawn, R. M., Capon, D. J. <strong>Structure of human factor VIII.</strong> Nature 312: 337-342, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438527</a>] [<a href="https://doi.org/10.1038/312337a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438527">Vehar et al., 1984</a>), this mutation is designated tyr342-to-ter (W342X). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6438527+8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0118" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0118 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, CYS329TYR
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852409 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852409;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010914" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010914" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010914</a>
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</span>
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</div>
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<span class="mim-text-font">
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a TGT-to-TAT transition at codon 329 in exon 8 of the A1 domain, resulting in tyrosine for cysteine-329. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0119" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0119 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, CYS348SER
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852410 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852410;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852410" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852410" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010915" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010915" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010915</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with 2.6% factor VIII activity, 3.2% factor VIII antigen, and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a TGT-to-TCT transversion at codon 329 in exon 8 of the A1 domain, resulting in serine for cysteine-329. Including the 19-amino acid signal peptide of the F8 gene (<a href="#132" class="mim-tip-reference" title="Vehar, G. A., Keyt, B., Eaton, D., Rodriguez, H., O'Brien, D. P., Rotblat, F., Oppermann, H., Keck, R., Wood, W. I., Harkins, R. N., Tuddenham, E. G. D., Lawn, R. M., Capon, D. J. <strong>Structure of human factor VIII.</strong> Nature 312: 337-342, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438527</a>] [<a href="https://doi.org/10.1038/312337a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438527">Vehar et al., 1984</a>), this mutation is designated cys348-to-ser (C348S). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6438527+7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0120" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0120 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, 2-BP DEL, FS
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906440 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906440;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906440" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906440" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010916" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010916" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010916</a>
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#58" class="mim-tip-reference" title="Higuchi, M., Wong, C., Kochhan, L., Olek, K., Aronis, S., Kasper, C. K., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>Characterization of mutations in the factor VIII gene by direct sequencing of amplified genomic DNA.</strong> Genomics 6: 65-71, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2105906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2105906</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90448-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2105906">Higuchi et al. (1990)</a> identified the deletion of 2 nucleotides (GA) resulting in a frameshift downstream from codon 341 in exon 8. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2105906" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0121" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0121 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, SER392TER
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28933668 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933668;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933668" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28933668" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010917" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010917" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010917</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 1 patient with hemophilia A (<a href="/entry/306700">306700</a>), <a href="#2" class="mim-tip-reference" title="Acquila, M., Caprino, D., Pecorara, M., Baudo, F., Morfini, M., Mori, P. G. <strong>Two novel mutations at 373 codon of FVIII gene detected by DGGE.</strong> Thromb. Haemost. 69: 392-393, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8497853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8497853</a>]" pmid="8497853">Acquila et al. (1993)</a> identified a TCA-to-TAA substitution at codon 373 in exon 8, resulting in a stop codon. Including the 19-amino acid signal peptide of the F8 gene (<a href="#132" class="mim-tip-reference" title="Vehar, G. A., Keyt, B., Eaton, D., Rodriguez, H., O'Brien, D. P., Rotblat, F., Oppermann, H., Keck, R., Wood, W. I., Harkins, R. N., Tuddenham, E. G. D., Lawn, R. M., Capon, D. J. <strong>Structure of human factor VIII.</strong> Nature 312: 337-342, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438527</a>] [<a href="https://doi.org/10.1038/312337a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438527">Vehar et al., 1984</a>), this mutation is designated ser392-to-ter (S392X). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6438527+8497853" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0122" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0122 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, SER373LEU
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28933668 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933668;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933668" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28933668" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010918 OR RCV003114182" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010918, RCV003114182" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010918...</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#2" class="mim-tip-reference" title="Acquila, M., Caprino, D., Pecorara, M., Baudo, F., Morfini, M., Mori, P. G. <strong>Two novel mutations at 373 codon of FVIII gene detected by DGGE.</strong> Thromb. Haemost. 69: 392-393, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8497853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8497853</a>]" pmid="8497853">Acquila et al. (1993)</a> found this mutation in a patient with 8% factor VIII activity and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a TCA-to-TTA transition at codon 373 in exon 8, resulting in leucine for serine-373. The mutation has been shown to abolish normal cleavage by thrombin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8497853" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0123" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0123 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, SER373PRO
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28933669 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933669;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933669" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28933669" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010919" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010919" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010919</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#65" class="mim-tip-reference" title="Johnson, D. J., Pemberton, S., Acquila, M., Mori, P. G., Tuddenham, E. G., O'Brien, D. P. <strong>Factor VIII S373L: mutation at P1' site confers thrombin cleavage resistance, causing mild haemophilia A.</strong> Thromb. Haemost. 71: 428-433, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8052958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8052958</a>]" pmid="8052958">Johnson et al. (1994)</a> found this mutation in a patient with 10% factor VIII activity, 100% factor VIII antigen, and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a TCA-to-CCA transition at codon 373 in exon 8, resulting in proline for serine-373. The mutation abolishes normal cleavage by thrombin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8052958" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0124 HEMOPHILIA A</strong>
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F8, 2-BP DEL, FS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906441 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906441;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906441" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906441" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010920" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010920" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010920</a>
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported the deletion of 2 nucleotides (AA), resulting in a frameshift downstream from codon 381-382 in exon 8. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0125" class="mim-anchor"></a>
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<strong>.0125 HEMOPHILIA A</strong>
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F8, ILE386SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28933670 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933670;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933670" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28933670" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010921" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010921" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010921</a>
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<p><a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> found this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by an ATT-to-AGT transversion at codon 386 in exon 8 of the A2 domain, resulting in serine for isoleucine-386. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0126" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0126 HEMOPHILIA A</strong>
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F8, GLU390GLY
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28933671 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933671;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933671" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28933671" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010922" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010922" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010922</a>
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</span>
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<div>
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<span class="mim-text-font">
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in 2 patients with less than 1-3.3% factor VIII activity and severe to moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a GAG-to-GGG transition at codon 390 in exon 8 of the A2 domain, resulting in glycine for glutamic acid-390. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0127" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0127 HEMOPHILIA A</strong>
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</h4>
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<div style="float: left;">
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F8, LEU412PHE
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28933672 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933672;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28933672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010923" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010923" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010923</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#54" class="mim-tip-reference" title="Higuchi, M., Antonarakis, S. E., Kasch, L., Oldenburg, J., Economou-Petersen, E., Olek, K., Arai, M., Inaba, H., Kazazian, H. H., Jr. <strong>Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 88: 8307-8311, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1924291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1924291</a>] [<a href="https://doi.org/10.1073/pnas.88.19.8307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1924291">Higuchi et al. (1991)</a> found this mutation in 2 patients with 5-10.5% factor VIII activity and moderate to mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a TTG-to-TTT transversion at codon 412 in exon 9 of the A2 domain, resulting in phenylalanine for leucine-412. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1924291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div>
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<div>
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<a id="0128" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0128 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, 1-BP DEL, FS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906442 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906442;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906442" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906442" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010924" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010924" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010924</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> identified the deletion of 1 nucleotide (G), resulting in a frameshift downstream from leucine-412 in exon 9. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<a id="0129" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0129 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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F8, LYS425ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28937272 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937272;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28937272" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28937272" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010925" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010925" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010925</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a> found this mutation in a patient with less than 1% factor VIII activity, 5% factor VIII antigen, and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a AAA-to-AGA transition at codon 425 in exon 9 of the A2 domain, resulting in arginine for lysine-425. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1908096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0130 HEMOPHILIA A</strong>
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F8, TYR431ASN
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs111033616 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033616;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs111033616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs111033616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010926" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010926" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010926</a>
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<p><a href="#108" class="mim-tip-reference" title="Pieneman, W. C., Reitsma, P. H., Briet, E. <strong>Double strand conformation polymorphism (DSCP) detects two point mutations at codon 280 (AAC-ATC) and at codon 431 (TAC-AAC) of the blood coagulation factor VIII gene.</strong> Thromb. Haemost. 69: 473-475, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8322269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8322269</a>]" pmid="8322269">Pieneman et al. (1993)</a> found this mutation in a patient with 4% factor VIII activity and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a TAC-to-AAC transversion at codon 431 in exon 9 of the A2 domain, resulting in asparagine for tyrosine-431. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8322269" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0131 HEMOPHILIA A</strong>
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F8, TYR473HIS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906443 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906443;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906443" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906443" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010927" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010927" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010927</a>
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<p><a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a> found this mutation in a patient with mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a TAT-to-CAT transition at codon 473 in exon 10 of the A2 domain, resulting in histidine for tyrosine-473. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1908096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0132" class="mim-anchor"></a>
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<strong>.0132 HEMOPHILIA A</strong>
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F8, TYR473CYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906444 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906444;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906444" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906444" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010928" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010928" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010928</a>
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<p><a href="#54" class="mim-tip-reference" title="Higuchi, M., Antonarakis, S. E., Kasch, L., Oldenburg, J., Economou-Petersen, E., Olek, K., Arai, M., Inaba, H., Kazazian, H. H., Jr. <strong>Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 88: 8307-8311, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1924291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1924291</a>] [<a href="https://doi.org/10.1073/pnas.88.19.8307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1924291">Higuchi et al. (1991)</a> found this mutation in 2 patients with 2.7-3.5% factor VIII activity and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a TAT-to-TGT transition at codon 473 in exon 10 of the A2 domain, resulting in cysteine for tyrosine-473. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1924291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0133" class="mim-anchor"></a>
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<strong>.0133 HEMOPHILIA A</strong>
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F8, ILE475THR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852413 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852413;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852413" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852413" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010929" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010929" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010929</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with 5-5.7% factor VIII activity, 6.9-8.8% factor VIII antigen, and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by an ATC-to-ACC transition at codon 475 in exon 10 of the A2 domain, resulting in threonine for isoleucine-475. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<h4>
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<strong>.0134 HEMOPHILIA A</strong>
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F8, GLY498ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852414 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852414;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852414" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852414" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010930 OR RCV000851700" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010930, RCV000851700" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010930...</a>
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<p><a href="#97" class="mim-tip-reference" title="Naylor, J. A., Green, P. M., Rizza, C. R., Giannelli, F. <strong>Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients.</strong> Hum. Molec. Genet. 2: 11-17, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490618</a>] [<a href="https://doi.org/10.1093/hmg/2.1.11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490618">Naylor et al. (1993)</a> found this mutation in a patient with 2% factor VIII activity and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a GGA-to-AGA transition in the F8 gene, resulting in a gly479-to-arg substitution. <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> stated that this mutation occurred in exon 10 of the A2 domain and had been reported in 2 other patients with hemophilia A. Including the 19-amino acid signal peptide of the F8 gene (<a href="#132" class="mim-tip-reference" title="Vehar, G. A., Keyt, B., Eaton, D., Rodriguez, H., O'Brien, D. P., Rotblat, F., Oppermann, H., Keck, R., Wood, W. I., Harkins, R. N., Tuddenham, E. G. D., Lawn, R. M., Capon, D. J. <strong>Structure of human factor VIII.</strong> Nature 312: 337-342, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438527</a>] [<a href="https://doi.org/10.1038/312337a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438527">Vehar et al., 1984</a>), this mutation is designated gly498-to-arg (G498R). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8490618+6438527+7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0135" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0135 HEMOPHILIA A</strong>
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</h4>
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F8, 11-BP DEL, FS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2124099163 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2124099163;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2124099163" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2124099163" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010931" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010931" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010931</a>
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> identified the deletion of 11 nucleotides (CCGTCCTTTGT) between codon 483 and 487 in exon 10. The deletion results in a frameshift. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0136 HEMOPHILIA A</strong>
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F8, IVS10AS, G-T, +1
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1414679955 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1414679955;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1414679955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1414679955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010932" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010932" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010932</a>
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<span class="mim-text-font">
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<p>In a patient with mild hemophilia A (<a href="/entry/306700">306700</a>), <a href="#37" class="mim-tip-reference" title="Economou, E. P., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>Detection of mutations in the factor VIII gene using single-stranded conformational polymorphism (SSCP).</strong> Genomics 13: 909-911, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1639429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1639429</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90189-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1639429">Economou et al. (1992)</a> identified a G-to-T transversion in codon 504. This mutation, which did not result in amino acid substitution, occurs in the first nucleotide of exon 11 and alters the sequence of the acceptor splice site of intron 10. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1639429" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0137" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0137 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, 1-BP INS, FS
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906445 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906445;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906445" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906445" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010933" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010933" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010933</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#37" class="mim-tip-reference" title="Economou, E. P., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>Detection of mutations in the factor VIII gene using single-stranded conformational polymorphism (SSCP).</strong> Genomics 13: 909-911, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1639429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1639429</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90189-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1639429">Economou et al. (1992)</a> identified the insertion of 1 nucleotide (G), resulting in a frameshift downstream from codon 513 or 514 in exon 11. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1639429" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0138" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0138 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, ASP525ASN
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852415 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852415;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852415" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852415" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010934" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010934" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010934</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with 6% factor VIII activity, 61% factor VIII antigen, and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a GAT-to-AAT transition at codon 525 in exon 11 of the A2 domain, resulting in asparagine for aspartic acid-525. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0139" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0139 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, ARG527TRP
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852416 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852416;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852416" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852416" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010935 OR RCV000852048 OR RCV003103711" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010935, RCV000852048, RCV003103711" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010935...</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#54" class="mim-tip-reference" title="Higuchi, M., Antonarakis, S. E., Kasch, L., Oldenburg, J., Economou-Petersen, E., Olek, K., Arai, M., Inaba, H., Kazazian, H. H., Jr. <strong>Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 88: 8307-8311, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1924291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1924291</a>] [<a href="https://doi.org/10.1073/pnas.88.19.8307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1924291">Higuchi et al. (1991)</a> found this mutation in a patient with 9.5-38% factor VIII activity, 43-245% factor VIII antigen, and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a CGG-to-TGG transition at codon 527 in exon 11 of the A2 domain, resulting in tryptophan for arginine-527. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. This mutation has also been found by others (<a href="#84" class="mim-tip-reference" title="McGinniss, M. J., Kazazian, H. H., Jr., Hoyer, L. W., Bi, L., Inaba, H., Antonarakis, S. E. <strong>Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A.</strong> Genomics 15: 392-398, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8449505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8449505</a>] [<a href="https://doi.org/10.1006/geno.1993.1073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8449505">McGinniss et al., 1993</a>; see also <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al., 1995</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7728145+1924291+8449505" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0140" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0140 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, ARG531CYS
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852417 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852417;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852417" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852417" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010936 OR RCV004595878" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010936, RCV004595878" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010936...</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#54" class="mim-tip-reference" title="Higuchi, M., Antonarakis, S. E., Kasch, L., Oldenburg, J., Economou-Petersen, E., Olek, K., Arai, M., Inaba, H., Kazazian, H. H., Jr. <strong>Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 88: 8307-8311, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1924291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1924291</a>] [<a href="https://doi.org/10.1073/pnas.88.19.8307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1924291">Higuchi et al. (1991)</a> found this mutation in 3 patients with 4.2-6.7% factor VIII activity and moderate to mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a CGC-to-TGC transition at codon 531 in exon 11 of the A2 domain, resulting in cysteine for arginine-531. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. This mutation has also been found by others (<a href="#37" class="mim-tip-reference" title="Economou, E. P., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>Detection of mutations in the factor VIII gene using single-stranded conformational polymorphism (SSCP).</strong> Genomics 13: 909-911, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1639429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1639429</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90189-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1639429">Economou et al., 1992</a> and <a href="#33" class="mim-tip-reference" title="Diamond, C., Kogan, S., Levinson, B., Gitschier, J. <strong>Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A.</strong> Hum. Mutat. 1: 248-257, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301932</a>] [<a href="https://doi.org/10.1002/humu.1380010312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301932">Diamond et al., 1992</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1639429+1924291+1301932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010937 OR RCV000757245" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010937, RCV000757245" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010937...</a>
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<p><a href="#54" class="mim-tip-reference" title="Higuchi, M., Antonarakis, S. E., Kasch, L., Oldenburg, J., Economou-Petersen, E., Olek, K., Arai, M., Inaba, H., Kazazian, H. H., Jr. <strong>Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 88: 8307-8311, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1924291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1924291</a>] [<a href="https://doi.org/10.1073/pnas.88.19.8307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1924291">Higuchi et al. (1991)</a> found this mutation in a patient with 9.2% factor VIII activity and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a CGC-to-GGC transversion at codon 531 in exon 11 of the A2 domain, resulting in glycine for arginine-531. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1924291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852418 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852418;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852418?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852418" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852418" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010938 OR RCV003656622 OR RCV005042025" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010938, RCV003656622, RCV005042025" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010938...</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with 23.5-32% factor VIII activity, 20-33.2% factor VIII antigen and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a CGC-to-CAC transition at codon 531 in exon 11 of the A2 domain, resulting in histidine for arginine-531. The G-to-A transition follows the rule of CG-to-CA mutations at CG dinucleotides. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852419 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852419;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852419?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852419" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852419" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010939 OR RCV000727106 OR RCV003934821" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010939, RCV000727106, RCV003934821" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010939...</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in 2 patients with mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a AGT-to-GGT transition at codon 535 in exon 11 of the A2 domain, resulting in glycine for serine-535. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852420 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852420;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010940" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010940" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010940</a>
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<p><a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a> found this mutation in a patient with less than 1% factor VIII activity, 5% factor VIII antigen, and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a GAT-to-GGT transition at codon 542 in exon 11 of the A2 domain, resulting in glycine for aspartic acid-542. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1908096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010941" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010941" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010941</a>
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<p>In a patient with hemophilia A (<a href="/entry/306700">306700</a>), <a href="#33" class="mim-tip-reference" title="Diamond, C., Kogan, S., Levinson, B., Gitschier, J. <strong>Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A.</strong> Hum. Mutat. 1: 248-257, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301932</a>] [<a href="https://doi.org/10.1002/humu.1380010312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301932">Diamond et al. (1992)</a> identified a GAA-to-TAA substitution at codon 557 in exon 11, resulting in a stop codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28937282 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937282;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28937282" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28937282" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010942" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010942" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010942</a>
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<p><a href="#84" class="mim-tip-reference" title="McGinniss, M. J., Kazazian, H. H., Jr., Hoyer, L. W., Bi, L., Inaba, H., Antonarakis, S. E. <strong>Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A.</strong> Genomics 15: 392-398, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8449505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8449505</a>] [<a href="https://doi.org/10.1006/geno.1993.1073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8449505">McGinniss et al. (1993)</a> found this mutation in a patient with 21% factor VIII activity, 175% factor VIII antigen, and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a TCT-to-TTT transition at codon 558 in exon 11 of the A2 domain, resulting in phenylalanine for serine-558. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8449505" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0147 HEMOPHILIA A</strong>
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F8, GLN565LYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852422 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852422;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852422" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852422" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010943" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010943" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010943</a>
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<p><a href="#54" class="mim-tip-reference" title="Higuchi, M., Antonarakis, S. E., Kasch, L., Oldenburg, J., Economou-Petersen, E., Olek, K., Arai, M., Inaba, H., Kazazian, H. H., Jr. <strong>Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 88: 8307-8311, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1924291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1924291</a>] [<a href="https://doi.org/10.1073/pnas.88.19.8307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1924291">Higuchi et al. (1991)</a> found this mutation in 2 patients with 6.8% factor VIII activity and moderate to mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a CAG-to-AAG transversion at codon 565 in exon 11 of the A2 domain, resulting in lysine for glutamine-565. This mutation has also been found by others (<a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al., 1995</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7728145+1924291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0148 HEMOPHILIA A</strong>
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F8, SER577PRO
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906446 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906446;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906446" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906446" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010944" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010944" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010944</a>
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<p><a href="#114" class="mim-tip-reference" title="Reiner, A. P., Thompson, A. R. <strong>Screening for nonsense mutations in patients with severe hemophilia A can provide rapid, direct carrier detection.</strong> Hum. Genet. 89: 88-94, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1349567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1349567</a>] [<a href="https://doi.org/10.1007/BF00207049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1349567">Reiner and Thompson (1992)</a> found this mutation in 5 patients with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a TCT-to-CCT transition at codon 577 in exon 12 of the A2 domain, resulting in proline for serine-577. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. This mutation has also been found by others (<a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al., 1995</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1349567+7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0149 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852424 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852424;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852424?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852424" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852424" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010945 OR RCV000852054" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010945, RCV000852054" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010945...</a>
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<p>In 5 patients with hemophilia A (<a href="/entry/306700">306700</a>), <a href="#105" class="mim-tip-reference" title="Pattinson, J. K., Millar, D. S., McVey, J. H., Grundy, C. B., Wieland, K., Mibashan, R. S., Martinowitz, U., Tan-Un, K., Vidaud, M., Goossens, M., Sampietro, M., Mannucci, P. M., and 17 others. <strong>The molecular genetic analysis of hemophilia A: a directed search strategy for the detection of point mutations in the human factor VIII gene.</strong> Blood 76: 2242-2248, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1979502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1979502</a>]" pmid="1979502">Pattinson et al. (1990)</a> identified a CGA-to-TGA substitution at codon 583 in exon 12, resulting in a stop codon. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. This mutation has also been found by others (<a href="#114" class="mim-tip-reference" title="Reiner, A. P., Thompson, A. R. <strong>Screening for nonsense mutations in patients with severe hemophilia A can provide rapid, direct carrier detection.</strong> Hum. Genet. 89: 88-94, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1349567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1349567</a>] [<a href="https://doi.org/10.1007/BF00207049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1349567">Reiner and Thompson, 1992</a>; see also <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al., 1995</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1349567+7728145+1979502" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0150 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852425 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852425;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852425" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852425" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010946" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010946" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010946</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a AGC-to-ATC transversion at codon 584 in exon 12 of the A2 domain, resulting in isoleucine for serine-584. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852426 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852426;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852426" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852426" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010947" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010947" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010947</a>
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<p><a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> found this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a TGG-to-TGC transversion at codon 585 in exon 12 of the A2 domain, resulting in cysteine for tryptophan-585. Including the 19-amino acid signal peptide of the F8 gene (<a href="#132" class="mim-tip-reference" title="Vehar, G. A., Keyt, B., Eaton, D., Rodriguez, H., O'Brien, D. P., Rotblat, F., Oppermann, H., Keck, R., Wood, W. I., Harkins, R. N., Tuddenham, E. G. D., Lawn, R. M., Capon, D. J. <strong>Structure of human factor VIII.</strong> Nature 312: 337-342, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438527</a>] [<a href="https://doi.org/10.1038/312337a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438527">Vehar et al., 1984</a>), this mutation is designated trp604-to-cys (W604C). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6438527+8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0152 HEMOPHILIA A</strong>
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F8, TYR586SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852427 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852427;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852427" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852427" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010948" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010948" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010948</a>
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<p><a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> found this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a TAC-to-TCC transversion at codon 586 in exon 12 of the A2 domain, resulting in serine for tyrosine-586. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0153 HEMOPHILIA A</strong>
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F8, ARG593CYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852428 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852428;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852428?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010949 OR RCV000413577 OR RCV000851933 OR RCV002247320 OR RCV004540992" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010949, RCV000413577, RCV000851933, RCV002247320, RCV004540992" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010949...</a>
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<p><a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a> found this mutation in a patient with mild to moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a CGC-to-TGC transition at codon 593 in exon 12 of the A2 domain, resulting in cysteine for arginine-593. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. This mutation has also been found by others (<a href="#97" class="mim-tip-reference" title="Naylor, J. A., Green, P. M., Rizza, C. R., Giannelli, F. <strong>Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients.</strong> Hum. Molec. Genet. 2: 11-17, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490618</a>] [<a href="https://doi.org/10.1093/hmg/2.1.11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490618">Naylor et al., 1993</a> and <a href="#33" class="mim-tip-reference" title="Diamond, C., Kogan, S., Levinson, B., Gitschier, J. <strong>Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A.</strong> Hum. Mutat. 1: 248-257, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301932</a>] [<a href="https://doi.org/10.1002/humu.1380010312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301932">Diamond et al., 1992</a>; see also <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al., 1995</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8490618+7728145+1301932+1908096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0154 HEMOPHILIA A</strong>
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F8, ASN612SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852429 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852429;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852429" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852429" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010950" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010950" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010950</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a AAC-to-AGC transition at codon 612 in exon 12 of the A2 domain, resulting in serine for asparagine-612. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0155 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2124090120 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2124090120;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2124090120" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2124090120" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010951" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010951" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010951</a>
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<p>In a patient with mild hemophilia A (<a href="/entry/306700">306700</a>), <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported a G-to-A transition. The mutation is at the fifth nucleotide of the donor splice site of intron 12 and results in abnormal splicing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0156 HEMOPHILIA A</strong>
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F8, VAL634ALA
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852430 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852430;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852430" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852430" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010952" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010952" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010952</a>
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<p><a href="#84" class="mim-tip-reference" title="McGinniss, M. J., Kazazian, H. H., Jr., Hoyer, L. W., Bi, L., Inaba, H., Antonarakis, S. E. <strong>Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A.</strong> Genomics 15: 392-398, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8449505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8449505</a>] [<a href="https://doi.org/10.1006/geno.1993.1073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8449505">McGinniss et al. (1993)</a> found this mutation in a patient with 5% factor VIII activity, 138% factor VIII antigen, and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a GTG-to-GCG transition at codon 634 in exon 13 of the A2 domain, resulting in alanine for valine-634. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8449505" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0157 HEMOPHILIA A</strong>
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F8, VAL634MET
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852431 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852431;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852431" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852431" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010953" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010953" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010953</a>
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<p><a href="#84" class="mim-tip-reference" title="McGinniss, M. J., Kazazian, H. H., Jr., Hoyer, L. W., Bi, L., Inaba, H., Antonarakis, S. E. <strong>Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A.</strong> Genomics 15: 392-398, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8449505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8449505</a>] [<a href="https://doi.org/10.1006/geno.1993.1073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8449505">McGinniss et al. (1993)</a> found a val634-to-met mutation in 2 patients with less than 1% factor VIII activity, 175% factor VIII antigen, and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a GTG-to-ATG transition at codon 634 in exon 13 of the A2 domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8449505" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0158" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0158 HEMOPHILIA A</strong>
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F8, TYR655TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852432 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852432;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852432" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852432" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010954" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010954" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010954</a>
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<span class="mim-text-font">
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<p>In 2 patients with hemophilia A (<a href="/entry/306700">306700</a>) (1 with inhibitors), <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported the substitution of TAC-to-TAG at codon 636 in exon 13, resulting in a stop codon. Including the 19-amino acid signal peptide of the F8 gene (<a href="#132" class="mim-tip-reference" title="Vehar, G. A., Keyt, B., Eaton, D., Rodriguez, H., O'Brien, D. P., Rotblat, F., Oppermann, H., Keck, R., Wood, W. I., Harkins, R. N., Tuddenham, E. G. D., Lawn, R. M., Capon, D. J. <strong>Structure of human factor VIII.</strong> Nature 312: 337-342, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438527</a>] [<a href="https://doi.org/10.1038/312337a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438527">Vehar et al., 1984</a>), this mutation is designated trp655-to-cys (W604C). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6438527+7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0159" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0159 HEMOPHILIA A</strong>
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</span>
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</h4>
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F8, ALA644VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852433 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852433;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852433" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852433" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010955" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010955" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010955</a>
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<p><a href="#54" class="mim-tip-reference" title="Higuchi, M., Antonarakis, S. E., Kasch, L., Oldenburg, J., Economou-Petersen, E., Olek, K., Arai, M., Inaba, H., Kazazian, H. H., Jr. <strong>Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 88: 8307-8311, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1924291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1924291</a>] [<a href="https://doi.org/10.1073/pnas.88.19.8307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1924291">Higuchi et al. (1991)</a> found this mutation in a patient with 14% factor VIII activity, 25% factor VIII antigen, and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a GCA-to-GTA transition at codon 644 in exon 13 of the A2 domain, resulting in valine for alanine-644. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1924291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0160" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0160 HEMOPHILIA A</strong>
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</h4>
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F8, 3-BP DEL, PHE652DEL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1476178386 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1476178386;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1476178386" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1476178386" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010956" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010956" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010956</a>
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<p>In a patient with 1.4% factor VIII activity, 12% factor VIII antigen, and severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#84" class="mim-tip-reference" title="McGinniss, M. J., Kazazian, H. H., Jr., Hoyer, L. W., Bi, L., Inaba, H., Antonarakis, S. E. <strong>Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A.</strong> Genomics 15: 392-398, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8449505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8449505</a>] [<a href="https://doi.org/10.1006/geno.1993.1073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8449505">McGinniss et al. (1993)</a> identified an in-frame deletion of 3 bp corresponding to codon 652 (TTC) in exon 13 of the A2 domain, resulting in the deletion of phenylalanine-652. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8449505" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div>
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<a id="0161" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0161 HEMOPHILIA A</strong>
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</h4>
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F8, PHE677LEU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852434 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852434;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852434" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852434" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010957" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010957" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010957</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with 5.1% factor VIII activity, 50.5% factor VIII antigen, and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a TTC-to-CTC transition at codon 658 in exon 13 of the A2 domain, resulting in leucine for phenylalanine-658. Including the 19-amino acid signal peptide of the F8 gene (<a href="#132" class="mim-tip-reference" title="Vehar, G. A., Keyt, B., Eaton, D., Rodriguez, H., O'Brien, D. P., Rotblat, F., Oppermann, H., Keck, R., Wood, W. I., Harkins, R. N., Tuddenham, E. G. D., Lawn, R. M., Capon, D. J. <strong>Structure of human factor VIII.</strong> Nature 312: 337-342, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438527</a>] [<a href="https://doi.org/10.1038/312337a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438527">Vehar et al., 1984</a>), this mutation is designated phe677-to-leu (F677L). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6438527+7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0162" class="mim-anchor"></a>
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<strong>.0162 HEMOPHILIA A</strong>
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F8, ARG698TRP
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852435 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852435;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852435?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852435" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852435" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010958 OR RCV000851590 OR RCV000851937 OR RCV002247321 OR RCV002281701 OR RCV002490350" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010958, RCV000851590, RCV000851937, RCV002247321, RCV002281701, RCV002490350" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010958...</a>
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<p><a href="#33" class="mim-tip-reference" title="Diamond, C., Kogan, S., Levinson, B., Gitschier, J. <strong>Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A.</strong> Hum. Mutat. 1: 248-257, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301932</a>] [<a href="https://doi.org/10.1002/humu.1380010312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301932">Diamond et al. (1992)</a> found this mutation in a patient with mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a CGG-to-TGG transition at codon 698 in exon 14 of the A2 domain, resulting in tryptophan for arginine-698. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0163" class="mim-anchor"></a>
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<strong>.0163 HEMOPHILIA A</strong>
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F8, ALA704THR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852436 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852436;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852436?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852436" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852436" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010959 OR RCV000852072 OR RCV001560529 OR RCV002490351" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010959, RCV000852072, RCV001560529, RCV002490351" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010959...</a>
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<p><a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a> found this mutation in 3 patients with a mild to moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a GCC-to-ACC transition at codon 704 in exon 14 of the A2 domain, resulting in threonine for alanine-704. The G-to-A transition follows the rule of CG-to-CA mutations at CG dinucleotides. See also <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7728145+1908096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0164" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0164 HEMOPHILIA A</strong>
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F8, GLU720LYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28937285 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937285;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs28937285?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28937285" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28937285" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010960 OR RCV004745152" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010960, RCV004745152" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010960...</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this glu720-to-lys mutation in 2 patients with 12.5-30% factor VIII activity, less than 20% factor VIII antigen, and a mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a GAG-to-AAG transition at codon 720 in exon 14 of the A2 domain. The G-to-A transition follows the rule of CG-to-CA mutations at CG dinucleotides. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0165" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0165 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs2228152 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2228152;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs2228152?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2228152" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2228152" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010961" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010961" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010961</a>
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<p>In a patient with hemophilia A (<a href="/entry/306700">306700</a>), <a href="#105" class="mim-tip-reference" title="Pattinson, J. K., Millar, D. S., McVey, J. H., Grundy, C. B., Wieland, K., Mibashan, R. S., Martinowitz, U., Tan-Un, K., Vidaud, M., Goossens, M., Sampietro, M., Mannucci, P. M., and 17 others. <strong>The molecular genetic analysis of hemophilia A: a directed search strategy for the detection of point mutations in the human factor VIII gene.</strong> Blood 76: 2242-2248, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1979502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1979502</a>]" pmid="1979502">Pattinson et al. (1990)</a> identified the substitution of CGA-to-TGA at codon 795 in exon 14, resulting in a stop codon. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1979502" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0166" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0166 HEMOPHILIA A</strong>
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</span>
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</h4>
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F8, 1-BP INS, FS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906447 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906447;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906447" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906447" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010962" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010962" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010962</a>
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#97" class="mim-tip-reference" title="Naylor, J. A., Green, P. M., Rizza, C. R., Giannelli, F. <strong>Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients.</strong> Hum. Molec. Genet. 2: 11-17, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490618</a>] [<a href="https://doi.org/10.1093/hmg/2.1.11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490618">Naylor et al. (1993)</a> identified the insertion of 1 nucleotide (A) at codon 961-2 or 3 in exon 14. The mutation results in a frameshift. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8490618" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0167 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906448 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906448;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906448" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906448" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010963" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010963" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010963</a>
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> identified the deletion of 2 nucleotides (AG) that results in a frameshift downstream from codon 969 in exon 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0168 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28933673 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933673;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs28933673?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933673" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28933673" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010964 OR RCV000601703 OR RCV002247322 OR RCV004791213" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010964, RCV000601703, RCV002247322, RCV004791213" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010964...</a>
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<p><a href="#54" class="mim-tip-reference" title="Higuchi, M., Antonarakis, S. E., Kasch, L., Oldenburg, J., Economou-Petersen, E., Olek, K., Arai, M., Inaba, H., Kazazian, H. H., Jr. <strong>Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 88: 8307-8311, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1924291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1924291</a>] [<a href="https://doi.org/10.1073/pnas.88.19.8307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1924291">Higuchi et al. (1991)</a> and <a href="#84" class="mim-tip-reference" title="McGinniss, M. J., Kazazian, H. H., Jr., Hoyer, L. W., Bi, L., Inaba, H., Antonarakis, S. E. <strong>Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A.</strong> Genomics 15: 392-398, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8449505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8449505</a>] [<a href="https://doi.org/10.1006/geno.1993.1073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8449505">McGinniss et al. (1993)</a> found this mutation in a patient with 2.4% factor VIII activity, 15% factor VIII antigen, and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a GAG-to-AAG transition at codon 1038 in exon 14 of the B domain, resulting in lysine for glutamic acid-1038. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1924291+8449505" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0169" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0169 HEMOPHILIA A</strong>
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F8, 2-BP DEL, FS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906449 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906449;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906449" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906449" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010965" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010965" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010965</a>
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> identified the deletion of 2 nucleotides (AA) resulting in a frameshift downstream from codon 1164 in exon 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0170" class="mim-anchor"></a>
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<strong>.0170 HEMOPHILIA A</strong>
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F8, 1-BP DEL, FS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs387906450 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906450;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs387906450?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906450" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906450" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010966 OR RCV000851976 OR RCV004721244" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010966, RCV000851976, RCV004721244" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010966...</a>
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<p>In 2 patients with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> identified the deletion of 1 nucleotide (A) resulting in a frameshift downstream from codon 1194 in exon 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0171" class="mim-anchor"></a>
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<strong>.0171 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906451 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906451;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906451" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906451" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010967" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010967" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010967</a>
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#97" class="mim-tip-reference" title="Naylor, J. A., Green, P. M., Rizza, C. R., Giannelli, F. <strong>Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients.</strong> Hum. Molec. Genet. 2: 11-17, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490618</a>] [<a href="https://doi.org/10.1093/hmg/2.1.11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490618">Naylor et al. (1993)</a> identified the deletion of 1 nucleotide (C) resulting in a frameshift downstream from codon 1212 in exon 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8490618" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2124049493 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2124049493;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2124049493" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2124049493" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010968" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010968" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010968</a>
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> identified the insertion of 2 nucleotides (AA) resulting in a frameshift downstream from codon 1324 in exon 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0173 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906452 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906452;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010969 OR RCV002490352" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010969, RCV002490352" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010969...</a>
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> identified the deletion of 4 nucleotides (TAGA) resulting in a frameshift downstream from codons 1355-6 in exon 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0174 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1360639935 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1360639935;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1360639935" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1360639935" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010970" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010970" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010970</a>
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a> identified the insertion of 1 nucleotide (A) resulting in a frameshift downstream from codon 1395 in exon 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1908096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0175" class="mim-anchor"></a>
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<strong>.0175 HEMOPHILIA A</strong>
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F8, 5-BP DEL, FS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906453 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906453;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906453" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906453" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010971" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010971" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010971</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported in a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) the deletion of 5 nucleotides (CTCTT) resulting in a frameshift downstream from codons 1412-4 in exon 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0176" class="mim-anchor"></a>
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<strong>.0176 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906454 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906454;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010972" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010972" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010972</a>
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#97" class="mim-tip-reference" title="Naylor, J. A., Green, P. M., Rizza, C. R., Giannelli, F. <strong>Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients.</strong> Hum. Molec. Genet. 2: 11-17, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490618</a>] [<a href="https://doi.org/10.1093/hmg/2.1.11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490618">Naylor et al. (1993)</a> identified the deletion of 4 nucleotides (AAGA) resulting in a frameshift downstream from codons 1422-5 in exon 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8490618" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0177" class="mim-anchor"></a>
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<strong>.0177 HEMOPHILIA A</strong>
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F8, 1-BP INS, A
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs387906455 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906455;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs387906455?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906455" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906455" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001807852 OR RCV002503301 OR RCV003104145" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001807852, RCV002503301, RCV003104145" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001807852...</a>
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<p><a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a> identified in 2 patients with severe hemophilia A (<a href="/entry/306700">306700</a>) the insertion of 1 nucleotide (A) between codons 1458 and 1460 in exon 14 resulting in a frameshift. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1908096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0178" class="mim-anchor"></a>
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<strong>.0178 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs387906455 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906455;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs387906455?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906455" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906455" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010974" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010974" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010974</a>
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<p>In 2 patients with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#54" class="mim-tip-reference" title="Higuchi, M., Antonarakis, S. E., Kasch, L., Oldenburg, J., Economou-Petersen, E., Olek, K., Arai, M., Inaba, H., Kazazian, H. H., Jr. <strong>Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 88: 8307-8311, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1924291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1924291</a>] [<a href="https://doi.org/10.1073/pnas.88.19.8307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1924291">Higuchi et al. (1991)</a> and <a href="#97" class="mim-tip-reference" title="Naylor, J. A., Green, P. M., Rizza, C. R., Giannelli, F. <strong>Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients.</strong> Hum. Molec. Genet. 2: 11-17, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490618</a>] [<a href="https://doi.org/10.1093/hmg/2.1.11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490618">Naylor et al. (1993)</a> identified the deletion of 1 nucleotide (A) resulting in a frameshift downstream from codons 1439, 1440 or 1441 in exon 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8490618+1924291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0179" class="mim-anchor"></a>
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<strong>.0179 HEMOPHILIA A</strong>
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F8, 2-BP DEL, GA
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2124048199 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2124048199;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2124048199" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2124048199" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010975" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010975" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010975</a>
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</span>
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</div>
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a> identified the deletion of 2 nucleotides (GA) between codons 1555 and 1556 in exon 14 resulting in a frameshift. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1908096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0180" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0180 HEMOPHILIA A</strong>
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</h4>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, 1-BP INS, FS
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</div>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397514036 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514036;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs397514036" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs397514036" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010976 OR RCV003103984" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010976, RCV003103984" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010976...</a>
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</span>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> identified the insertion of 1 nucleotide (A) resulting in a frameshift downstream from codon 1590 in exon 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0181" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0181 HEMOPHILIA A</strong>
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<span class="mim-text-font">
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F8, 1-BP DEL, FS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906456 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906456;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906456" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906456" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010977" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010977" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010977</a>
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</span>
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<div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> identified the deletion of 1 nucleotide (C) resulting in a frameshift downstream from codon 1601 in exon 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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<a id="0182" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0182 HEMOPHILIA A</strong>
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</span>
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</h4>
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F8, GLU161TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852438 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852438;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852438" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852438" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010978" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010978" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010978</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with hemophilia A (<a href="/entry/306700">306700</a>), <a href="#74" class="mim-tip-reference" title="Lavergne, J. M., Bahnak, B. R., Vidaud, M., Laurian, Y., Meyer, D. <strong>A directed search for mutations in hemophilia A using restriction enzyme analysis and denaturing gradient gel electrophoresis: a study of seven exons in the factor VIII gene of 170 cases.</strong> Nouv. Rev. Franc. Hemat. 34: 85-91, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1523102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1523102</a>]" pmid="1523102">Lavergne et al. (1992)</a> identified the substitution of GAG-to-TAG at codon 1615 in exon 14, resulting in a stop codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1523102" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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<div>
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<div>
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<a id="0183" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0183 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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F8, ARG1689HIS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs111033614 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033614;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs111033614?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs111033614" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs111033614" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010979 OR RCV000851813 OR RCV001091839 OR RCV003914826" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010979, RCV000851813, RCV001091839, RCV003914826" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010979...</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#120" class="mim-tip-reference" title="Schwaab, R., Oldenburg, J., Tuddenham, E. G. D., Brackmann, H. H., Olek, K. <strong>Mutations in haemophilia A.</strong> Brit. J. Haemat. 83: 450-458, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8485051/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8485051</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1993.tb04670.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8485051">Schwaab et al. (1993)</a> found this mutation in 3 patients with 7-11% factor VIII activity, 130-165% factor VIII antigen, and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by a CGC-to-CAC transition at codon 1689 in exon 14 of the A3 domain, resulting in histidine for arginine-1689. The G-to-A transition follows the rule of CG-to-CA mutations at CG dinucleotides. The mutation has been shown to abolish normal cleavage by thrombin at the light chain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8485051" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852439 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852439;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852439" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852439" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010980" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010980" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010980</a>
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<p>In 2 patients with hemophilia A (<a href="/entry/306700">306700</a>) and inhibitors, <a href="#105" class="mim-tip-reference" title="Pattinson, J. K., Millar, D. S., McVey, J. H., Grundy, C. B., Wieland, K., Mibashan, R. S., Martinowitz, U., Tan-Un, K., Vidaud, M., Goossens, M., Sampietro, M., Mannucci, P. M., and 17 others. <strong>The molecular genetic analysis of hemophilia A: a directed search strategy for the detection of point mutations in the human factor VIII gene.</strong> Blood 76: 2242-2248, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1979502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1979502</a>]" pmid="1979502">Pattinson et al. (1990)</a> identified the substitution of CGA to TGA at codon 1696 in exon 14, resulting in a stop codon. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. This mutation has also been found by others (<a href="#97" class="mim-tip-reference" title="Naylor, J. A., Green, P. M., Rizza, C. R., Giannelli, F. <strong>Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients.</strong> Hum. Molec. Genet. 2: 11-17, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490618</a>] [<a href="https://doi.org/10.1093/hmg/2.1.11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490618">Naylor et al., 1993</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8490618+1979502" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0185 HEMOPHILIA A</strong>
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F8, ARG1696GLY
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852439 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852439;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852439" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852439" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010981 OR RCV003114183" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010981, RCV003114183" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010981...</a>
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<p><a href="#114" class="mim-tip-reference" title="Reiner, A. P., Thompson, A. R. <strong>Screening for nonsense mutations in patients with severe hemophilia A can provide rapid, direct carrier detection.</strong> Hum. Genet. 89: 88-94, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1349567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1349567</a>] [<a href="https://doi.org/10.1007/BF00207049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1349567">Reiner and Thompson (1992)</a> found this mutation in a patient with 17% factor VIII activity and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CGA-to-TGA transition at codon 1696 in exon 14 of the A3 domain, resulting in glycine for arginine-1696. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1349567" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0186 HEMOPHILIA A</strong>
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F8, IVS14AS, A-G, -2
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2073039685 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2073039685;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2073039685" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2073039685" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010982" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010982" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010982</a>
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<p>In a patient with less than 1% factor VIII activity, less than 2.5% factor VIII antigen, and severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported the substitution of A to G at the second nucleotide of the acceptor splice site of intron 14, resulting in abnormal splicing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0187 HEMOPHILIA A</strong>
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F8, GLY1769ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852440 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852440;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852440" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852440" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010983" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010983" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010983</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in 4 patients with 21-26% factor VIII activity, 14.5-26% factor VIII antigen, and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a GGA-to-AGA transition at codon 1750 in exon 15 of the A3 domain, resulting in arginine for glycine-1750. Including the 19-amino acid signal peptide of the F8 gene (<a href="#132" class="mim-tip-reference" title="Vehar, G. A., Keyt, B., Eaton, D., Rodriguez, H., O'Brien, D. P., Rotblat, F., Oppermann, H., Keck, R., Wood, W. I., Harkins, R. N., Tuddenham, E. G. D., Lawn, R. M., Capon, D. J. <strong>Structure of human factor VIII.</strong> Nature 312: 337-342, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438527</a>] [<a href="https://doi.org/10.1038/312337a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438527">Vehar et al., 1984</a>), this mutation is designated gly1769-to-arg (G1769R). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6438527+7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<span class="mim-font">
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<strong>.0188 HEMOPHILIA A</strong>
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F8, LEU1756VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28937287 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937287;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28937287" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28937287" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010984" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010984" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010984</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with 5% factor VIII activity, 1.5% factor VIII antigen, and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a TTG-to-GTG transversion at codon 1756 in exon 15 of the A3 domain, resulting in valine for leucine-1756. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0189" class="mim-anchor"></a>
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<strong>.0189 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852441 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852441;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852441" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852441" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010985" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010985" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010985</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with 18.5% factor VIII activity, and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a TTG-to-TTC transversion at codon 1756 in exon 15 of the A3 domain, resulting in phenylalanine for leucine-1756. Including the 19-amino acid signal peptide of the F8 gene (<a href="#132" class="mim-tip-reference" title="Vehar, G. A., Keyt, B., Eaton, D., Rodriguez, H., O'Brien, D. P., Rotblat, F., Oppermann, H., Keck, R., Wood, W. I., Harkins, R. N., Tuddenham, E. G. D., Lawn, R. M., Capon, D. J. <strong>Structure of human factor VIII.</strong> Nature 312: 337-342, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438527</a>] [<a href="https://doi.org/10.1038/312337a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438527">Vehar et al., 1984</a>), this mutation is designated leu1775-to-phe (L1775F). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6438527+7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0190 HEMOPHILIA A</strong>
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F8, GLY1760GLU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28937289 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937289;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28937289" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28937289" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010986" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010986" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010986</a>
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<p><a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> found this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a GGG-to-GAG transition at codon 1760 in exon 15 of the A3 domain, resulting in glutamic acid for glycine-1760. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0191" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0191 HEMOPHILIA A</strong>
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F8, ARG1781HIS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852442 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852442;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852442" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852442" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010987 OR RCV001552643 OR RCV003430635" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010987, RCV001552643, RCV003430635" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010987...</a>
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<p><a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a> found this mutation in 4 patients with 2-2.5% factor VIII activity, 4.7-5.4% factor VIII antigen, and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CGT-to-CAT transition at codon 1781 in exon 16 of the A3 domain, resulting in histidine for arginine-1781. The G-to-A transition follows the rule of CG-to-CA mutations at CG dinucleotides. See also <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7728145+1908096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0192" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0192 HEMOPHILIA A</strong>
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F8, ARG1781CYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852443 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852443;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852443?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852443" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852443" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010988" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010988" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010988</a>
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<p><a href="#66" class="mim-tip-reference" title="Jonsdottir, S., Diamond, C., Levinson, B., Magnusson, S., Jensson, O., Gitschier, J. <strong>Missense mutations causing mild hemophilia A in Iceland detected by denaturing gradient gel electrophoresis.</strong> Hum. Mutat. 1: 506-508, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301960/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301960</a>] [<a href="https://doi.org/10.1002/humu.1380010610" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301960">Jonsdottir et al. (1992)</a> found this mutation in a patient with 4-7% factor VIII activity and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CGT-to-TGT transition at codon 1781 in exon 16 of the A3 domain, resulting in cysteine for arginine-1781. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301960" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0193" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0193 HEMOPHILIA A</strong>
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F8, ARG1781GLY
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852443 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852443;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852443?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852443" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852443" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010989" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010989" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010989</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with 6% factor VIII activity and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CGT-to-GGT transversion at codon 1781 in exon 16 of the A3 domain, resulting in glycine for arginine-1781. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0194 HEMOPHILIA A</strong>
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F8, SER1784TYR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852444 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852444;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852444" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852444" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010990" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010990" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010990</a>
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<p><a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a> found this mutation in a patient with less than 1% factor VIII activity and clinically a severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a TCC-to-TAC transversion at codon 1784 in exon 16 of the A3 domain, resulting in tyrosine for serine-1784. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1908096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0195" class="mim-anchor"></a>
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<strong>.0195 HEMOPHILIA A</strong>
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F8, LEU1789PHE
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852445 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852445;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852445" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852445" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010991" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010991" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010991</a>
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<p><a href="#33" class="mim-tip-reference" title="Diamond, C., Kogan, S., Levinson, B., Gitschier, J. <strong>Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A.</strong> Hum. Mutat. 1: 248-257, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301932</a>] [<a href="https://doi.org/10.1002/humu.1380010312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301932">Diamond et al. (1992)</a> and <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> found this mutation in 3 patients with 7.2% factor VIII activity and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CTT-to-TTT transition at codon 1789 in exon 16 of the A3 domain, resulting in phenylalanine for leucine-1789. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8307558+1301932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0196" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0196 HEMOPHILIA A</strong>
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</h4>
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F8, GLN1796TER
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852446 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852446;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852446" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852446" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010992" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010992" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010992</a>
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</span>
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<span class="mim-text-font">
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<p>In a patient with hemophilia A (<a href="/entry/306700">306700</a>) and inhibitors, <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> identified the substitution of CAG-to-TAG at codon 1796 in exon 16, resulting in a stop codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0197" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0197 HEMOPHILIA A</strong>
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F8, MET1823ILE
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28933674 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933674;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933674" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28933674" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010993" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010993" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010993</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> found this mutation in a patient with 4.6% factor VIII activity and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation is caused by an ATG-to-ATA transition at codon 1823 in exon 16 of the A3 domain, resulting in isoleucine for methionine-1823. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0198" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0198 HEMOPHILIA A</strong>
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F8, PRO1825SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28933675 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933675;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933675" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28933675" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010994 OR RCV000851817" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010994, RCV000851817" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010994...</a>
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</span>
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<span class="mim-text-font">
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<p><a href="#54" class="mim-tip-reference" title="Higuchi, M., Antonarakis, S. E., Kasch, L., Oldenburg, J., Economou-Petersen, E., Olek, K., Arai, M., Inaba, H., Kazazian, H. H., Jr. <strong>Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 88: 8307-8311, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1924291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1924291</a>] [<a href="https://doi.org/10.1073/pnas.88.19.8307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1924291">Higuchi et al. (1991)</a> found this mutation in a patient with 15% factor VIII activity and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CCC-to-TCC transition at codon 1825 in exon 16 of the A3 domain, resulting in serine for proline-1825. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1924291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0199" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0199 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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F8, THR1826PRO
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28933676 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933676;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933676" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28933676" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010995" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010995" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010995</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#37" class="mim-tip-reference" title="Economou, E. P., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>Detection of mutations in the factor VIII gene using single-stranded conformational polymorphism (SSCP).</strong> Genomics 13: 909-911, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1639429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1639429</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90189-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1639429">Economou et al. (1992)</a> found this mutation in a patient with mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by an ACT-to-CCT transversion at codon 1826 in exon 16 of the A3 domain, resulting in proline for threonine-1826. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1639429" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0200" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0200 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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F8, LYS1827TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906457 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906457;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010996" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010996" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010996</a>
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</span>
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<span class="mim-text-font">
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<p>In 2 patients with hemophilia A (<a href="/entry/306700">306700</a>) and inhibitors, <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> identified the mutation AAA to TAA at codon 1827 in exon 16, resulting in a stop codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0201" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0201 HEMOPHILIA A</strong>
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F8, ALA1834VAL
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28933677 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933677;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933677" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28933677" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010997" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010997" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010997</a>
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</div>
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<span class="mim-text-font">
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<p><a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> found this mutation in a patient with 18% factor VIII activity and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a GCC-to-GTC transition at codon 1834 in exon 16 of the A3 domain, resulting in valine for alanine-1834. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0202" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0202 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, IVS16DS, G-A, -1
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2123997676 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2123997676;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2123997676" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2123997676" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010998" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010998" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010998</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 patients with 9-18% factor VIII activity, 5.9% factor VIII antigen, and mild hemophilia A (<a href="/entry/306700">306700</a>), <a href="#54" class="mim-tip-reference" title="Higuchi, M., Antonarakis, S. E., Kasch, L., Oldenburg, J., Economou-Petersen, E., Olek, K., Arai, M., Inaba, H., Kazazian, H. H., Jr. <strong>Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 88: 8307-8311, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1924291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1924291</a>] [<a href="https://doi.org/10.1073/pnas.88.19.8307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1924291">Higuchi et al. (1991)</a> and <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported a G-to-A substitution at the -1 nucleotide of the donor splice site of intron 16, resulting in abnormal splicing. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7728145+1924291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0203" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0203 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, ASP1846ASN
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28933678 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933678;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933678" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28933678" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000010999" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010999" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010999</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a GAT-to-AAT transition at codon 1846 in exon 17 of the A3 domain, resulting in asparagine for aspartic acid-1846. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0204" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0204 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, ASP1846TYR
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28933678 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933678;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933678" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28933678" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011000" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011000" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011000</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a GAT-to-TAT transversion at codon 1846 in exon 17 of the A3 domain, resulting in tyrosine for aspartic acid-1846. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0205" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0205 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, HIS1848ARG
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28933679 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933679;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933679" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28933679" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011001 OR RCV003480027" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011001, RCV003480027" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011001...</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#54" class="mim-tip-reference" title="Higuchi, M., Antonarakis, S. E., Kasch, L., Oldenburg, J., Economou-Petersen, E., Olek, K., Arai, M., Inaba, H., Kazazian, H. H., Jr. <strong>Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 88: 8307-8311, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1924291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1924291</a>] [<a href="https://doi.org/10.1073/pnas.88.19.8307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1924291">Higuchi et al. (1991)</a> found this mutation in a patient with 1-5% factor VIII activity and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CAC-to-CGC transition at codon 1848 in exon 17 of the A3 domain, resulting in arginine for histidine-1848. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1924291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0206" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0206 HEMOPHILIA A</strong>
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</span>
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</h4>
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F8, PRO1854ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28933680 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933680;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933680" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28933680" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011002" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011002" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011002</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CCC-to-CGC transversion at codon 1854 in exon 17 of the A3 domain, resulting in arginine for proline-1854. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0207" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0207 HEMOPHILIA A</strong>
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</h4>
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</div>
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<div style="float: left;">
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F8, 1-BP INS, FS
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906458 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906458;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906458" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906458" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011003" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011003" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011003</a>
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</span>
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<span class="mim-text-font">
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported in 1 patient with severe hemophilia A (<a href="/entry/306700">306700</a>) the insertion of 1 nucleotide (T) resulting in a frameshift downstream from codon 1855 in exon 17. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div>
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<a id="0208" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0208 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, GLN1874TER
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852448 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852448;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852448" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852448" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011004" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011004" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011004</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 1 patient with hemophilia A (<a href="/entry/306700">306700</a>) and inhibitors, <a href="#97" class="mim-tip-reference" title="Naylor, J. A., Green, P. M., Rizza, C. R., Giannelli, F. <strong>Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients.</strong> Hum. Molec. Genet. 2: 11-17, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490618</a>] [<a href="https://doi.org/10.1093/hmg/2.1.11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490618">Naylor et al. (1993)</a> identified the substitution of CAG-to-TAG at codon 1874 in exon 17, resulting in a stop codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8490618" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0209" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0209 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, GLU1885LYS
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28933681 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933681;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933681" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28933681" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011005" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011005" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011005</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> found this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a GAG-to-AAG transition at codon 1885 in exon 17 of the A3 domain, resulting in lysine for glutamic acid-1885. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0210" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0210 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, 1-BP INS, FS
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906459 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906459;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906459" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906459" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011006" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011006" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011006</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a> identified in 1 patient with severe hemophilia A (<a href="/entry/306700">306700</a>) the insertion of 1 nucleotide (A) at codon 1907 in exon resulting in a frameshift. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1908096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div>
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<a id="0211" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0211 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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F8, ASN1922SER
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28933682 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933682;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933682" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28933682" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011007 OR RCV004791214" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011007, RCV004791214" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011007...</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a> and <a href="#33" class="mim-tip-reference" title="Diamond, C., Kogan, S., Levinson, B., Gitschier, J. <strong>Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A.</strong> Hum. Mutat. 1: 248-257, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301932</a>] [<a href="https://doi.org/10.1002/humu.1380010312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301932">Diamond et al. (1992)</a> identified this mutation in 2 patients with less than 1% factor VIII activity and severe-to-moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation was an AAT-to-AGT transition at codon 1922 in exon 18 of the F8 gene, resulting in an asn1922-to-ser (N1922S) substitution in the A3 domain of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1301932+1908096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#125" class="mim-tip-reference" title="Summers, R. J., Meeks, S. L., Healey, J. F., Brown, H. C., Parker, E. T., Kempton, C. L., Doering, C. B., Lollar, P. <strong>Factor VIII A3 domain substitution N1922S results in hemophilia A due to domain-specific misfolding and hyposecretion of functional protein.</strong> Blood 117: 3190-3198, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21217077/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21217077</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21217077[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood-2010-09-307074" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21217077">Summers et al. (2011)</a> noted that N1922 lies at the interface of 2 A3 subdomains in F8 and that the A3 and adjacent C1 domains form an extensive hydrophobic interface. By expression in baby hamster kidney cells, they found that F8 with the N1922S mutation (F8-N1922S) was weakly secreted compared with wildtype F8, although secreted F8-N1922S showed normal or near-normal activity. Wildtype F8 followed the classic secretory pathway; however, F8-N1922S was delayed in the endoplasmic reticulum (ER), prior to processing and packaging in the Golgi. Use of conformation-specific monoclonal antibodies revealed that the delay in the ER was due to a defect in folding of the A3 domain and the adjacent C1 domain. <a href="#125" class="mim-tip-reference" title="Summers, R. J., Meeks, S. L., Healey, J. F., Brown, H. C., Parker, E. T., Kempton, C. L., Doering, C. B., Lollar, P. <strong>Factor VIII A3 domain substitution N1922S results in hemophilia A due to domain-specific misfolding and hyposecretion of functional protein.</strong> Blood 117: 3190-3198, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21217077/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21217077</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21217077[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood-2010-09-307074" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21217077">Summers et al. (2011)</a> concluded that the N1922S substitution results in poor secretion of a functional protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21217077" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0212 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28937294 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937294;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28937294" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28937294" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011008" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011008" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011008</a>
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<p><a href="#93" class="mim-tip-reference" title="Nafa, K., Baudis, M., Deburgrave, N., Bardin, J.-M., Sultan, Y., Kaplan, J.-C., Delpech, M. <strong>A novel mutation (Arg-to-Leu in exon 18) in factor VIII gene responsible for moderate hemophilia A.</strong> Hum. Mutat. 1: 77-78, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301194</a>] [<a href="https://doi.org/10.1002/humu.1380010114" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301194">Nafa et al. (1992)</a> found this mutation in a patient with 7% factor VIII activity and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CGA-to-CTA transversion at codon 1941 in exon 18 of the A3 domain, resulting in leucine for arginine-1941. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301194" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0213 HEMOPHILIA A</strong>
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F8, TRP1961TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852449 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852449;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852449" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852449" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011009" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011009" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011009</a>
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<p>In a patient with hemophilia A (<a href="/entry/306700">306700</a>), <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> identified the substitution of TGG-to-TAG at codon 1942 in exon 18, resulting in a stop codon. Including the 19-amino acid signal peptide of the F8 gene (<a href="#132" class="mim-tip-reference" title="Vehar, G. A., Keyt, B., Eaton, D., Rodriguez, H., O'Brien, D. P., Rotblat, F., Oppermann, H., Keck, R., Wood, W. I., Harkins, R. N., Tuddenham, E. G. D., Lawn, R. M., Capon, D. J. <strong>Structure of human factor VIII.</strong> Nature 312: 337-342, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438527</a>] [<a href="https://doi.org/10.1038/312337a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438527">Vehar et al., 1984</a>), this mutation is designated trp1961-to-ter (W1961X). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6438527+8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0214 HEMOPHILIA A</strong>
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F8, GLY1948ASP
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs111033615 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033615;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs111033615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs111033615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011010" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011010" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011010</a>
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<p><a href="#32" class="mim-tip-reference" title="David, D., Moreira, I., Lalloz, M. R., Rosa, H. A., Schwaab, R., Morais, S., Diniz, M. J., de Deus, G., Campos, M., Lavinha, J. <strong>Analysis of the essential sequences of the factor VIII gene in twelve haemophilia A patients by single-stranded conformation polymorphism.</strong> Blood Coagul. Fibrinolysis 5: 257-264, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8054459/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8054459</a>] [<a href="https://doi.org/10.1097/00001721-199404000-00016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8054459">David et al. (1994)</a> found this mutation in a patient with 7.4% factor VIII activity, 46.7% factor VIII antigen, and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a GGC-to-GAC transition at codon 1948 in exon 18 of the A3 domain, resulting in aspartic acid for glycine-1948. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8054459" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0215 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852450 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852450;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852450" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852450" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011011" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011011" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011011</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with 6% factor VIII activity and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a GGA-to-GTA transversion at codon 1960 in exon 18 of the A3 domain, resulting in valine for glycine-1960. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0216 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852451 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852451;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852451" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852451" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011012" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011012" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011012</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with 15.5% factor VIII activity, 7.8% factor VIII antigen, and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CAT-to-TAT transition at codon 1961 in exon 18 of the A3 domain, resulting in tyrosine for histidine-1961. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0217 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852452 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852452;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011013" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011013" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011013</a>
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<p>In 7 patients with hemophilia A (<a href="/entry/306700">306700</a>) (3 with inhibitors), <a href="#114" class="mim-tip-reference" title="Reiner, A. P., Thompson, A. R. <strong>Screening for nonsense mutations in patients with severe hemophilia A can provide rapid, direct carrier detection.</strong> Hum. Genet. 89: 88-94, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1349567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1349567</a>] [<a href="https://doi.org/10.1007/BF00207049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1349567">Reiner and Thompson (1992)</a> identified the mutation of CGA to TGA at codon 1966 in exon 18, resulting in a stop codon. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. This mutation has also been found by others (<a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al., 1993</a>; <a href="#97" class="mim-tip-reference" title="Naylor, J. A., Green, P. M., Rizza, C. R., Giannelli, F. <strong>Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients.</strong> Hum. Molec. Genet. 2: 11-17, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490618</a>] [<a href="https://doi.org/10.1093/hmg/2.1.11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490618">Naylor et al., 1993</a>; <a href="#120" class="mim-tip-reference" title="Schwaab, R., Oldenburg, J., Tuddenham, E. G. D., Brackmann, H. H., Olek, K. <strong>Mutations in haemophilia A.</strong> Brit. J. Haemat. 83: 450-458, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8485051/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8485051</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1993.tb04670.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8485051">Schwaab et al., 1993</a>; and <a href="#32" class="mim-tip-reference" title="David, D., Moreira, I., Lalloz, M. R., Rosa, H. A., Schwaab, R., Morais, S., Diniz, M. J., de Deus, G., Campos, M., Lavinha, J. <strong>Analysis of the essential sequences of the factor VIII gene in twelve haemophilia A patients by single-stranded conformation polymorphism.</strong> Blood Coagul. Fibrinolysis 5: 257-264, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8054459/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8054459</a>] [<a href="https://doi.org/10.1097/00001721-199404000-00016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8054459">David et al., 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8054459+1349567+8485051+8490618+8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0218 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs387906460 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906460;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs387906460?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906460" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906460" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011014" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011014" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011014</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> identified in 2 patients with severe hemophilia A (<a href="/entry/306700">306700</a>) the deletion of 1 nucleotide (A) resulting in a frameshift downstream from codon 1967-1968 in exon 19. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0219 HEMOPHILIA A</strong>
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F8, 1-BP DEL, FS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906461 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906461;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906461" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906461" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011015" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011015" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011015</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported in 1 patient with severe hemophilia A (<a href="/entry/306700">306700</a>) the deletion of 1 nucleotide (G) resulting in a frameshift downstream from codon 1998 in exon 19. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0220 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606791 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606791;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs267606791" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs267606791" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011016" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011016" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011016</a>
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<p>In 1 patient with hemophilia A (<a href="/entry/306700">306700</a>), <a href="#97" class="mim-tip-reference" title="Naylor, J. A., Green, P. M., Rizza, C. R., Giannelli, F. <strong>Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients.</strong> Hum. Molec. Genet. 2: 11-17, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490618</a>] [<a href="https://doi.org/10.1093/hmg/2.1.11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490618">Naylor et al. (1993)</a> identified the mutation of GAA to TAA at codon 1987 in exon 19, resulting in a stop codon and exon 19 skipping. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8490618" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0221" class="mim-anchor"></a>
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<strong>.0221 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852453 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852453;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852453" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852453" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011017" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011017" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011017</a>
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<p><a href="#54" class="mim-tip-reference" title="Higuchi, M., Antonarakis, S. E., Kasch, L., Oldenburg, J., Economou-Petersen, E., Olek, K., Arai, M., Inaba, H., Kazazian, H. H., Jr. <strong>Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 88: 8307-8311, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1924291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1924291</a>] [<a href="https://doi.org/10.1073/pnas.88.19.8307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1924291">Higuchi et al. (1991)</a> and <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in 3 patients with less than 1-3.4% factor VIII activity and moderate to severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CGG-to-TGG transition at codon 1997 in exon 19 of the A3 domain, resulting in tryptophan for arginine-1997. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7728145+1924291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0222 HEMOPHILIA A</strong>
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F8, ASN2019SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852454 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852454;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011018" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011018" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011018</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with 5% factor VIII activity, 3.3% factor VIII antigen, and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a AAT-to-AGT transition at codon 2019 in exon 19 of the A3 domain, resulting in serine for asparagine-2019. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0223 HEMOPHILIA A</strong>
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F8, TRP2065ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852455 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852455;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852455" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852455" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011019" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011019" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011019</a>
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<p><a href="#33" class="mim-tip-reference" title="Diamond, C., Kogan, S., Levinson, B., Gitschier, J. <strong>Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A.</strong> Hum. Mutat. 1: 248-257, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301932</a>] [<a href="https://doi.org/10.1002/humu.1380010312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301932">Diamond et al. (1992)</a> found this mutation in a patient with moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a TGG-to-CGG transition at codon 2046 in exon 21 of the C1 domain, resulting in arginine for tryptophan-2046. Including the 19-amino acid signal peptide of the F8 gene (<a href="#132" class="mim-tip-reference" title="Vehar, G. A., Keyt, B., Eaton, D., Rodriguez, H., O'Brien, D. P., Rotblat, F., Oppermann, H., Keck, R., Wood, W. I., Harkins, R. N., Tuddenham, E. G. D., Lawn, R. M., Capon, D. J. <strong>Structure of human factor VIII.</strong> Nature 312: 337-342, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438527</a>] [<a href="https://doi.org/10.1038/312337a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438527">Vehar et al., 1984</a>), this mutation is designated trp2065-to-arg (W2065R). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6438527+1301932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0224" class="mim-anchor"></a>
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<strong>.0224 HEMOPHILIA A</strong>
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F8, SER2069PHE
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852456 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852456;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852456" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852456" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011020" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011020" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011020</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a TCT-to-TTT transition at codon 2069 in exon 21 of the C1 domain, resulting in phenylalanine for serine-2069. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0225" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0225 HEMOPHILIA A</strong>
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</h4>
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F8, ASP2074GLY
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852457 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852457;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011021" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011021" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011021</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> found this mutation in 2 patients with 4.5-9% factor VIII activity, 1.7-15.2% factor VIII antigen, and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a GAT-to-GGT transition at codon 2074 in exon 22 of the C1 domain, resulting in glycine for aspartic acid-2074. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0226" class="mim-anchor"></a>
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<strong>.0226 HEMOPHILIA A</strong>
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F8, PHE2120LEU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852458 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852458;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852458" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852458" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011022" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011022" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011022</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in 2 patients with 7-11% factor VIII activity, 5.3% factor VIII antigen, and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a TTT-to-TTG transversion at codon 2101 in exon 22 of the C1 domain, resulting in leucine for phenylalanine-2101. Including the 19-amino acid signal peptide of the F8 gene (<a href="#132" class="mim-tip-reference" title="Vehar, G. A., Keyt, B., Eaton, D., Rodriguez, H., O'Brien, D. P., Rotblat, F., Oppermann, H., Keck, R., Wood, W. I., Harkins, R. N., Tuddenham, E. G. D., Lawn, R. M., Capon, D. J. <strong>Structure of human factor VIII.</strong> Nature 312: 337-342, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438527</a>] [<a href="https://doi.org/10.1038/312337a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438527">Vehar et al., 1984</a>), this mutation is designated phe2120-to-leu (F2120L). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6438527+7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0227 HEMOPHILIA A</strong>
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F8, TYR2124CYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852459 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852459;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852459?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852459" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852459" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011023 OR RCV001508071" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011023, RCV001508071" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011023...</a>
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<p><a href="#97" class="mim-tip-reference" title="Naylor, J. A., Green, P. M., Rizza, C. R., Giannelli, F. <strong>Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients.</strong> Hum. Molec. Genet. 2: 11-17, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490618</a>] [<a href="https://doi.org/10.1093/hmg/2.1.11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490618">Naylor et al. (1993)</a> found this mutation in a patient with 14% factor VIII activity and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a TAT-to-TGT transition at codon 2105 in exon 22 of the C1 domain, resulting in cysteine for tyrosine-2105. Including the 19-amino acid signal peptide of the F8 gene (<a href="#132" class="mim-tip-reference" title="Vehar, G. A., Keyt, B., Eaton, D., Rodriguez, H., O'Brien, D. P., Rotblat, F., Oppermann, H., Keck, R., Wood, W. I., Harkins, R. N., Tuddenham, E. G. D., Lawn, R. M., Capon, D. J. <strong>Structure of human factor VIII.</strong> Nature 312: 337-342, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438527</a>] [<a href="https://doi.org/10.1038/312337a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438527">Vehar et al., 1984</a>), this mutation is designated tyr2124-to-cys (Y2124C). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8490618+6438527" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0228" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0228 HEMOPHILIA A</strong>
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F8, SER2119TYR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852460 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852460;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852460" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852460" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011024" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011024" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011024</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in 3 patients with 3-8% factor VIII activity, 9.2-13.2% factor VIII antigen, and mild to moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a TCC-to-TAC transversion at codon 2119 in exon 22 of the C1 domain, resulting in tyrosine for serine-2119. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0229" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0229 HEMOPHILIA A</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, 2-BP DEL, FS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906462 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906462;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906462" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906462" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011025" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011025" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011025</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> identified in 1 patient with severe hemophilia A (<a href="/entry/306700">306700</a>) the deletion of 2 nucleotides (TC) resulting in a frameshift downstream from serine-2119 in exon 22. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0230" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0230 HEMOPHILIA A</strong>
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<div style="float: left;">
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F8, 2-BP DEL, FS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906463 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906463;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906463" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906463" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011026" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011026" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011026</a>
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<p><a href="#129" class="mim-tip-reference" title="Tuddenham, E. G. D., Cooper, D. N., Gitschier, J., Higuchi, M., Hoyer, L. W., Yoshioka, A., Peake, I. R., Schwaab, R., Olek, K., Kazazian, H. H., Lavergne, J.-M., Giannelli, F., Antonarakis, S. E. <strong>Haemophilia A: database of nucleotide substitutions, deletions, insertions and rearrangements of the factor VIII gene.</strong> Nucleic Acids Res. 19: 4821-4833, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1923751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1923751</a>] [<a href="https://doi.org/10.1093/nar/19.18.4821" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1923751">Tuddenham et al. (1991)</a> identified in 1 patient with severe hemophilia A (<a href="/entry/306700">306700</a>) the deletion of 2 nucleotides (AA) resulting in a frameshift downstream from codon 2136 in exon 23. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1923751" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0231" class="mim-anchor"></a>
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<h4>
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<strong>.0231 HEMOPHILIA A</strong>
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F8, ARG2169HIS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852461 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852461;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852461" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852461" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011028 OR RCV000851846 OR RCV003147281 OR RCV005049328" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011028, RCV000851846, RCV003147281, RCV005049328" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011028...</a>
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</span>
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<span class="mim-text-font">
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> stated that this mutation had been reported in 10 patients with less than 1 to 7% factor VIII activity and severe to mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CGT-to-CAT transition at codon 2150 in exon 23 of the C1 domain, resulting in histidine for arginine-2150. The G-to-A transition follows the rule of CG-to-CA mutations at CG dinucleotides. This mutation was reported by <a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a>, <a href="#98" class="mim-tip-reference" title="Naylor, J., Brinke, A., Hassock, S., Green, P. M., Giannelli, F. <strong>Characteristic mRNA abnormality found in half the patients with severe haemophilia A is due to large DNA inversions.</strong> Hum. Molec. Genet. 2: 1773-1778, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8281136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8281136</a>] [<a href="https://doi.org/10.1093/hmg/2.11.1773" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8281136">Naylor et al. (1993)</a>, <a href="#33" class="mim-tip-reference" title="Diamond, C., Kogan, S., Levinson, B., Gitschier, J. <strong>Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A.</strong> Hum. Mutat. 1: 248-257, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301932</a>] [<a href="https://doi.org/10.1002/humu.1380010312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301932">Diamond et al. (1992)</a>; and <a href="#66" class="mim-tip-reference" title="Jonsdottir, S., Diamond, C., Levinson, B., Magnusson, S., Jensson, O., Gitschier, J. <strong>Missense mutations causing mild hemophilia A in Iceland detected by denaturing gradient gel electrophoresis.</strong> Hum. Mutat. 1: 506-508, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301960/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301960</a>] [<a href="https://doi.org/10.1002/humu.1380010610" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301960">Jonsdottir et al. (1992)</a>. Including the 19-amino acid signal peptide of the F8 gene (<a href="#132" class="mim-tip-reference" title="Vehar, G. A., Keyt, B., Eaton, D., Rodriguez, H., O'Brien, D. P., Rotblat, F., Oppermann, H., Keck, R., Wood, W. I., Harkins, R. N., Tuddenham, E. G. D., Lawn, R. M., Capon, D. J. <strong>Structure of human factor VIII.</strong> Nature 312: 337-342, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438527</a>] [<a href="https://doi.org/10.1038/312337a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438527">Vehar et al., 1984</a>), this mutation is designated arg2169-to-his (R2169H). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7728145+1908096+6438527+1301932+1301960+8281136" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852462 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852462;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852462" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852462" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011029" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011029" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011029</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with 3% factor VIII activity, 5.6% factor VIII antigen, and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CCA-to-CAA transversion at codon 2153 in exon 23 of the C1 domain, resulting in glutamine for proline-2153. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852463 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852463;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852463" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852463" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011030" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011030" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011030</a>
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<p><a href="#66" class="mim-tip-reference" title="Jonsdottir, S., Diamond, C., Levinson, B., Magnusson, S., Jensson, O., Gitschier, J. <strong>Missense mutations causing mild hemophilia A in Iceland detected by denaturing gradient gel electrophoresis.</strong> Hum. Mutat. 1: 506-508, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301960/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301960</a>] [<a href="https://doi.org/10.1002/humu.1380010610" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301960">Jonsdottir et al. (1992)</a> found this mutation in a patient with 6% factor VIII activity and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by an ACT-to-ATT transition at codon 2154 in exon 23 of the C1 domain, resulting in isoleucine for threonine-2154. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301960" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852464 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852464;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011031 OR RCV003103985" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011031, RCV003103985" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011031...</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> stated that this mutation had been reported in 12 patients with 6 to 26% factor VIII activity, less than 5 to 15.7% factor VIII antigen, and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CGC-to-TGC transition at codon 2159 in exon 23 of the C1 domain, resulting in cysteine for arginine-2159. The mutation was reported by <a href="#54" class="mim-tip-reference" title="Higuchi, M., Antonarakis, S. E., Kasch, L., Oldenburg, J., Economou-Petersen, E., Olek, K., Arai, M., Inaba, H., Kazazian, H. H., Jr. <strong>Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 88: 8307-8311, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1924291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1924291</a>] [<a href="https://doi.org/10.1073/pnas.88.19.8307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1924291">Higuchi et al. (1991)</a>, <a href="#84" class="mim-tip-reference" title="McGinniss, M. J., Kazazian, H. H., Jr., Hoyer, L. W., Bi, L., Inaba, H., Antonarakis, S. E. <strong>Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A.</strong> Genomics 15: 392-398, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8449505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8449505</a>] [<a href="https://doi.org/10.1006/geno.1993.1073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8449505">McGinniss et al. (1993)</a>; <a href="#33" class="mim-tip-reference" title="Diamond, C., Kogan, S., Levinson, B., Gitschier, J. <strong>Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A.</strong> Hum. Mutat. 1: 248-257, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301932</a>] [<a href="https://doi.org/10.1002/humu.1380010312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301932">Diamond et al. (1992)</a>; and <a href="#66" class="mim-tip-reference" title="Jonsdottir, S., Diamond, C., Levinson, B., Magnusson, S., Jensson, O., Gitschier, J. <strong>Missense mutations causing mild hemophilia A in Iceland detected by denaturing gradient gel electrophoresis.</strong> Hum. Mutat. 1: 506-508, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301960/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301960</a>] [<a href="https://doi.org/10.1002/humu.1380010610" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301960">Jonsdottir et al. (1992)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7728145+8449505+1301932+1301960+1924291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852465 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852465;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852465?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852465" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852465" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011027" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011027" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011027</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with 12% factor VIII activity, 4.8% factor VIII antigen, and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CGC-to-CTC transversion at codon 2159 in exon 23 of the C1 domain, resulting in leucine for arginine-2159. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0236 HEMOPHILIA A</strong>
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F8, ARG2159HIS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852465 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852465;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852465?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852465" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852465" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011032 OR RCV000852179 OR RCV003114184" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011032, RCV000852179, RCV003114184" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011032...</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with 22% factor VIII activity, 11.9% factor VIII antigen, and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CGC-to-CAC transition at codon 2159 in exon 23 of the C1 domain, resulting in histidine for arginine-2159. The G-to-A transition follows the rule of CG-to-CA mutations at CG dinucleotides. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0237" class="mim-anchor"></a>
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<strong>.0237 HEMOPHILIA A</strong>
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F8, ARG2163HIS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852466 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852466;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852466" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852466" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011033 OR RCV004821959" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011033, RCV004821959" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011033...</a>
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</span>
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<span class="mim-text-font">
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in 2 patients with 5% factor VIII antigen and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CGC-to-CAC transition at codon 2163 in exon 23 of the C1 domain, resulting in histidine for arginine-2163. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0238" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0238 HEMOPHILIA A</strong>
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</h4>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, ARG2163CYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852467 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852467;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852467?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852467" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852467" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011034 OR RCV002247323" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011034, RCV002247323" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011034...</a>
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</span>
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<div>
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<span class="mim-text-font">
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<p><a href="#113" class="mim-tip-reference" title="Reiner, A. P., Stray, S. M., Thompson, A. R. <strong>Three missense mutations in Arg codons of the factor VIII gene of mild to moderately severe hemophilia A patients.</strong> Thromb. Res. 66: 93-99, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1412186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1412186</a>] [<a href="https://doi.org/10.1016/0049-3848(92)90159-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1412186">Reiner et al. (1992)</a> found this mutation in a patient with 1% factor VIII activity, less than 10% factor VIII antigen, and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CGC-to-TGC transition at codon 2163 in exon 23 of the C1 domain, resulting in cysteine for arginine-2163. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1412186" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0239" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0239 HEMOPHILIA A</strong>
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</span>
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</h4>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, ALA2192PRO
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852468 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852468;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852468" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852468" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011035" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011035" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011035</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> found this mutation in a patient with 1% factor VIII activity and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a GCT-to-CCT transversion at codon 2192 in exon 24 of the C2 domain, resulting in proline for alanine-2192. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div>
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<a id="0240" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0240 HEMOPHILIA A</strong>
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</h4>
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F8, 3-BP DEL, PRO220 DEL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1229477261 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1229477261;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1229477261" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1229477261" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011036" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011036" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011036</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 3 patients with less than 1% factor VIII activity and severe-to-moderate hemophilia A (<a href="/entry/306700">306700</a>), <a href="#37" class="mim-tip-reference" title="Economou, E. P., Kazazian, H. H., Jr., Antonarakis, S. E. <strong>Detection of mutations in the factor VIII gene using single-stranded conformational polymorphism (SSCP).</strong> Genomics 13: 909-911, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1639429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1639429</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90189-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1639429">Economou et al. (1992)</a> and <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> identified an in-frame deletion of 3-bp corresponding to codon 2205 (TctcCT) in exon 24 of the C2 domain, resulting in the deletion of proline-2205. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1639429+8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div>
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<div>
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<a id="0241" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0241 HEMOPHILIA A</strong>
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</h4>
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F8, ARG2209LEU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852358 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852358;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852358" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852358" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011037" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011037" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011037</a>
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<p><a href="#88" class="mim-tip-reference" title="Millar, D. S., Zoll, B., Martinowitz, U., Kakkar, V. V., Cooper, D. N. <strong>The molecular genetics of haemophilia A: screening for point mutations in the factor VIII gene using the restriction enzyme TaqI.</strong> Hum. Genet. 87: 607-612, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1840568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1840568</a>] [<a href="https://doi.org/10.1007/BF00209022" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1840568">Millar et al. (1991)</a> found this mutation in a patient with 3% factor VIII activity, 2.5% factor VIII antigen, and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CGA-to-CTA transversion at codon 2209 in exon 24 of the C2 domain, resulting in leucine for arginine-2209. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1840568" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0242 HEMOPHILIA A</strong>
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F8, ARG2209GLY
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852355 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852355;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852355" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852355" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011038" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011038" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011038</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CGA-to-GGA transversion at codon 2209 in exon 24 of the C2 domain, resulting in glycine for arginine-2209. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0243 HEMOPHILIA A</strong>
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<div style="float: left;">
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F8, 1-BP DEL, FS
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906464 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906464;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011039" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011039" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011039</a>
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</span>
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<span class="mim-text-font">
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported in 1 patient with severe hemophilia A (<a href="/entry/306700">306700</a>) the deletion of 1 nucleotide (G) resulting in a frameshift downstream from codon 2214 in exon 24. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0244" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0244 HEMOPHILIA A</strong>
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<div style="float: left;">
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F8, TRP2248CYS
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852469 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852469;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852469" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852469" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011040 OR RCV000851849 OR RCV003114185" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011040, RCV000851849, RCV003114185" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011040...</a>
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</span>
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<span class="mim-text-font">
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<p><a href="#95" class="mim-tip-reference" title="Naylor, J. A., Green, P. M., Montandon, A. J., Rizza, C. R., Giannelli, F. <strong>Detection of three novel mutations in two haemophilia A patients by rapid screening of whole essential region of factor VIII gene.</strong> Lancet 337: 635-639, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1671991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1671991</a>] [<a href="https://doi.org/10.1016/0140-6736(91)92450-g" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1671991">Naylor et al. (1991)</a> and <a href="#33" class="mim-tip-reference" title="Diamond, C., Kogan, S., Levinson, B., Gitschier, J. <strong>Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A.</strong> Hum. Mutat. 1: 248-257, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301932</a>] [<a href="https://doi.org/10.1002/humu.1380010312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301932">Diamond et al. (1992)</a> found this mutation in 2 patients with 3% factor VIII activity, moderate hemophilia A (<a href="/entry/306700">306700</a>), and inhibitors in 1 out of the 2. The mutation was caused by a TGG-to-TGT transversion at codon 2229 in exon 25 of the C2 domain, resulting in cysteine for tryptophan-2229. Including the 19-amino acid signal peptide of the F8 gene (<a href="#132" class="mim-tip-reference" title="Vehar, G. A., Keyt, B., Eaton, D., Rodriguez, H., O'Brien, D. P., Rotblat, F., Oppermann, H., Keck, R., Wood, W. I., Harkins, R. N., Tuddenham, E. G. D., Lawn, R. M., Capon, D. J. <strong>Structure of human factor VIII.</strong> Nature 312: 337-342, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438527</a>] [<a href="https://doi.org/10.1038/312337a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438527">Vehar et al., 1984</a>), this mutation is designated trp2248-to-cys (W2248C). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1671991+6438527+1301932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0245" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0245 HEMOPHILIA A</strong>
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</span>
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</h4>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, GLN2246ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852470 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852470;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852470" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852470" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011041 OR RCV001701638" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011041, RCV001701638" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011041...</a>
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</span>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with 4.5% factor VIII activity, 1.1% factor VIII antigen, and moderate hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CAG-to-CGG transition at codon 2246 in exon 25 of the C2 domain, resulting in arginine for glutamine-2246. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0246" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0246 HEMOPHILIA A</strong>
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</h4>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, 2-BP DEL, FS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906465 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906465;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906465" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906465" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011042" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011042" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011042</a>
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</span>
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<div>
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<span class="mim-text-font">
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<p><a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> identified in 1 patient with severe hemophilia A (<a href="/entry/306700">306700</a>) the deletion of 2 nucleotides (AG) resulting in a frameshift downstream from glutamine-2246 in exon 25. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0247 HEMOPHILIA A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852471 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852471;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852471" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852471" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011043" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011043" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011043</a>
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<p>In 1 patient with hemophilia A (<a href="/entry/306700">306700</a>), <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported the mutation of CAG-to-TAG at codon 2270 in exon 25, resulting in a stop codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0248 HEMOPHILIA A</strong>
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F8, 5-BP DEL, FS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906466 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906466;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906466" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906466" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011044" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011044" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011044</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported in 1 patient with severe hemophilia A (<a href="/entry/306700">306700</a>) the deletion of 5 nucleotides (AAATC) resulting in a frameshift downstream from codon 2285-86 or 87 in exon 26. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0249" class="mim-anchor"></a>
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<strong>.0249 HEMOPHILIA A</strong>
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F8, PRO2300LEU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852472 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852472;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852472" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852472" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011045 OR RCV000851613 OR RCV001701721" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011045, RCV000851613, RCV001701721" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011045...</a>
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<p><a href="#54" class="mim-tip-reference" title="Higuchi, M., Antonarakis, S. E., Kasch, L., Oldenburg, J., Economou-Petersen, E., Olek, K., Arai, M., Inaba, H., Kazazian, H. H., Jr. <strong>Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.</strong> Proc. Nat. Acad. Sci. 88: 8307-8311, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1924291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1924291</a>] [<a href="https://doi.org/10.1073/pnas.88.19.8307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1924291">Higuchi et al. (1991)</a> found this mutation in a patient with 7.5% factor VIII activity and mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CCG-to-CTG transition at codon 2300 in exon 26 of the C2 domain, resulting in leucine for proline-2300. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1924291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0250" class="mim-anchor"></a>
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<strong>.0250 HEMOPHILIA A</strong>
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F8, ARG2304CYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852473 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852473;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852473?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852473" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852473" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011046" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011046" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011046</a>
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</span>
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<span class="mim-text-font">
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<p><a href="#55" class="mim-tip-reference" title="Higuchi, M., Kazazian, H. H., Jr., Kasch, L., Warren, T. C., McGinniss, M. J., Phillips, J. A., III, Kasper, C., III, Janco, R., Antonarakis, S. E. <strong>Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.</strong> Proc. Nat. Acad. Sci. 88: 7405-7409, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1908096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1908096</a>] [<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1908096">Higuchi et al. (1991)</a> and <a href="#113" class="mim-tip-reference" title="Reiner, A. P., Stray, S. M., Thompson, A. R. <strong>Three missense mutations in Arg codons of the factor VIII gene of mild to moderately severe hemophilia A patients.</strong> Thromb. Res. 66: 93-99, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1412186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1412186</a>] [<a href="https://doi.org/10.1016/0049-3848(92)90159-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1412186">Reiner et al. (1992)</a> found this mutation in 2 patients with less than 1% factor VIII activity, less than 10% factor VIII antigen, and severe hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CGC-to-TGC transition at codon 2304 in exon 26 of the C2 domain, resulting in cysteine for arginine-2304. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1412186+1908096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0251" class="mim-anchor"></a>
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<strong>.0251 HEMOPHILIA A</strong>
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F8, ARG2304HIS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852474 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852474;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852474" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852474" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011047" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011047" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011047</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported this mutation in a patient with mild hemophilia A (<a href="/entry/306700">306700</a>). The mutation was caused by a CGC-to-CAC transition at codon 2304 in exon 26 of the C2 domain, resulting in histidine for arginine-2304. The G-to-A transition follows the rule of CG-to-CA mutations at CG dinucleotides. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0252" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0252 HEMOPHILIA A</strong>
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F8, EX1-6DEL
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011048" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011048" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011048</a>
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</span>
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</div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) (patient H238) and factor VIII inhibitors, <a href="#87" class="mim-tip-reference" title="Millar, D. S., Steinbrecher, R. A., Wieland, K., Grundy, C. B., Martinowitz, U., Krawczak, M., Zoll, B., Whitmore, D., Stephenson, J., Mibashan, R. S., Kakkar, V. V., Cooper, D. N. <strong>The molecular genetic analysis of haemophilia A: characterization of six partial deletions in the factor VIII gene.</strong> Hum. Genet. 86: 219-227, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2125022/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2125022</a>] [<a href="https://doi.org/10.1007/BF00197709" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2125022">Millar et al. (1990)</a> found a deletion of exons 1-6 of the factor VIII gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2125022" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div>
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<a id="0253" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0253 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, EX2-4DEL
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011049" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011049" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011049</a>
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</span>
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</div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) (patient TWN11) and factor VIII inhibitors, <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> found a deletion of exons 2-4 of the factor VIII gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0254" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0254 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, EX3-5DEL
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011050" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011050" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011050</a>
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|
</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) (patient H151), <a href="#87" class="mim-tip-reference" title="Millar, D. S., Steinbrecher, R. A., Wieland, K., Grundy, C. B., Martinowitz, U., Krawczak, M., Zoll, B., Whitmore, D., Stephenson, J., Mibashan, R. S., Kakkar, V. V., Cooper, D. N. <strong>The molecular genetic analysis of haemophilia A: characterization of six partial deletions in the factor VIII gene.</strong> Hum. Genet. 86: 219-227, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2125022/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2125022</a>] [<a href="https://doi.org/10.1007/BF00197709" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2125022">Millar et al. (1990)</a> found a deletion of exons 3-5 of the factor VIII gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2125022" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0255" class="mim-anchor"></a>
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|
<h4>
|
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<span class="mim-font">
|
|
<strong>.0255 HEMOPHILIA A</strong>
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|
</span>
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</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
|
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F8, EX4-10DEL
|
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</div>
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</span>
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<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011051" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011051" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011051</a>
|
|
</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) (patient TWN27) and factor VIII inhibitors, <a href="#80" class="mim-tip-reference" title="Lin, S.-W., Lin, S.-R., Shen, M.-C. <strong>Characterization of genetic defects of hemophilia A in patients of Chinese origin.</strong> Genomics 18: 496-504, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307558</a>]" pmid="8307558">Lin et al. (1993)</a> found a deletion of exons 4-10 of the factor VIII gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<a id="0256" class="mim-anchor"></a>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0256 HEMOPHILIA A</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
F8, EX5-13DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011052" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011052" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011052</a>
|
|
</span>
|
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|
|
</div>
|
|
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|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) (patient H571) and factor VIII inhibitors, <a href="#87" class="mim-tip-reference" title="Millar, D. S., Steinbrecher, R. A., Wieland, K., Grundy, C. B., Martinowitz, U., Krawczak, M., Zoll, B., Whitmore, D., Stephenson, J., Mibashan, R. S., Kakkar, V. V., Cooper, D. N. <strong>The molecular genetic analysis of haemophilia A: characterization of six partial deletions in the factor VIII gene.</strong> Hum. Genet. 86: 219-227, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2125022/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2125022</a>] [<a href="https://doi.org/10.1007/BF00197709" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2125022">Millar et al. (1990)</a> found a deletion of exons 5-13 of the factor VIII gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2125022" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
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</div>
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<div>
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|
<br />
|
|
</div>
|
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|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0257" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0257 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
F8, EX10DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011053" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011053" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011053</a>
|
|
</span>
|
|
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|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) (patient 149), <a href="#72" class="mim-tip-reference" title="Krepelova, A., Vorlova, Z., Zavadil, J., Brdicka, R. <strong>Factor VIII gene deletions in haemophilia A patients in Czechoslovakia.</strong> Brit. J. Haemat. 81: 271-276, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1643024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1643024</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1992.tb08219.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1643024">Krepelova et al. (1992)</a> found a deletion of exon 10 of the factor VIII gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1643024" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0258" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0258 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
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|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
F8, EX14-21DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011054" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011054" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011054</a>
|
|
</span>
|
|
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|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) (patient H229) and factor VIII inhibitors, <a href="#87" class="mim-tip-reference" title="Millar, D. S., Steinbrecher, R. A., Wieland, K., Grundy, C. B., Martinowitz, U., Krawczak, M., Zoll, B., Whitmore, D., Stephenson, J., Mibashan, R. S., Kakkar, V. V., Cooper, D. N. <strong>The molecular genetic analysis of haemophilia A: characterization of six partial deletions in the factor VIII gene.</strong> Hum. Genet. 86: 219-227, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2125022/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2125022</a>] [<a href="https://doi.org/10.1007/BF00197709" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2125022">Millar et al. (1990)</a> found a deletion of exons 14-21 of the factor VIII gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2125022" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
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</div>
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<div>
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<br />
|
|
</div>
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|
|
</div>
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|
|
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|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0259" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0259 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
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|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
F8, EX14-22DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011055" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011055" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011055</a>
|
|
</span>
|
|
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|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) (patient H20) and factor VIII inhibitors, <a href="#94" class="mim-tip-reference" title="Nafa, K., Meriane, F., Reghis, A., Benabadji, M., Demenais, F., Guilloud-Bataille, M., Sultan, Y., Kaplan, J. C., Delpech, M. <strong>Investigation of factor VIIIC gene restriction fragment length polymorphisms and search for deletions in hemophiliac subjects in Algeria.</strong> Hum. Genet. 84: 401-405, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1969840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1969840</a>] [<a href="https://doi.org/10.1007/BF00195808" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1969840">Nafa et al. (1990)</a> found a deletion of exons 14-22 of the factor VIII gene. See also <a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1969840+7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
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</div>
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<div>
|
|
<br />
|
|
</div>
|
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|
</div>
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|
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<div>
|
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|
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|
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<div>
|
|
<a id="0260" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0260 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
F8, EX15-22DEL
|
|
</div>
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|
|
</span>
|
|
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011056" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011056" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011056</a>
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<p><a href="#7" class="mim-tip-reference" title="Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D. <strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong> Hum. Mutat. 5: 1-22, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>] [<a href="https://doi.org/10.1002/humu.1380050102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7728145">Antonarakis et al. (1995)</a> reported 3 patients with severe hemophilia A (<a href="/entry/306700">306700</a>) who had a deletion of exons 15-22 of the factor VIII gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0261" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0261 HEMOPHILIA A</strong>
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</h4>
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F8, EX16-26DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011057" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011057" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011057</a>
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) (patient HDX3) and factor VIII inhibitors, <a href="#40" class="mim-tip-reference" title="Figueiredo, M. S., Bernardi, F., Zago, M. A. <strong>A novel deletion of FVIII gene associated with variable levels of FVIII inhibitor.</strong> Europ. J. Haemat. 48: 152-154, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1559571/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1559571</a>] [<a href="https://doi.org/10.1111/j.1600-0609.1992.tb00587.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1559571">Figueiredo et al. (1992)</a> found a deletion of exons 16-26 of the factor VIII gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1559571" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0262" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0262 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, EX18-19DEL
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011058" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011058" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011058</a>
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</span>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) (patient 5b), <a href="#52" class="mim-tip-reference" title="Grover, H., Phillips, M. A., Lillicrap, D. P., Giles, A. R., Garvey, M. B., Teitel, J., Rivard, G., Blanchette, V., White, B. N., Holden, J. J. A. <strong>Carrier deletion of haemophilia A using DNA markers in families with an isolated affected male.</strong> Clin. Genet. 32: 10-19, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2887317/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2887317</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1987.tb03316.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2887317">Grover et al. (1987)</a> found a deletion of exons 18-19 of the factor VIII gene. This deletion may extend to exon 22. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2887317" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div>
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<div>
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<a id="0263" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0263 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, EX16DEL
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011059" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011059" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011059</a>
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</span>
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</div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) (patient HD10), <a href="#120" class="mim-tip-reference" title="Schwaab, R., Oldenburg, J., Tuddenham, E. G. D., Brackmann, H. H., Olek, K. <strong>Mutations in haemophilia A.</strong> Brit. J. Haemat. 83: 450-458, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8485051/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8485051</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1993.tb04670.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8485051">Schwaab et al. (1993)</a> found a deletion of exon 16 of the factor VIII gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8485051" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0264" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0264 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, EX19-21DEL
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011060" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011060" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011060</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) (patient H58) and factor VIII inhibitors, <a href="#87" class="mim-tip-reference" title="Millar, D. S., Steinbrecher, R. A., Wieland, K., Grundy, C. B., Martinowitz, U., Krawczak, M., Zoll, B., Whitmore, D., Stephenson, J., Mibashan, R. S., Kakkar, V. V., Cooper, D. N. <strong>The molecular genetic analysis of haemophilia A: characterization of six partial deletions in the factor VIII gene.</strong> Hum. Genet. 86: 219-227, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2125022/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2125022</a>] [<a href="https://doi.org/10.1007/BF00197709" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2125022">Millar et al. (1990)</a> found a deletion of exons 19-21 of the factor VIII gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2125022" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0265" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0265 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, EX23-24DEL
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011061" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011061" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011061</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) (patient HA711), <a href="#74" class="mim-tip-reference" title="Lavergne, J. M., Bahnak, B. R., Vidaud, M., Laurian, Y., Meyer, D. <strong>A directed search for mutations in hemophilia A using restriction enzyme analysis and denaturing gradient gel electrophoresis: a study of seven exons in the factor VIII gene of 170 cases.</strong> Nouv. Rev. Franc. Hemat. 34: 85-91, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1523102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1523102</a>]" pmid="1523102">Lavergne et al. (1992)</a> found a deletion of exons 23-24 of the factor VIII gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1523102" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0266" class="mim-anchor"></a>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0266 HEMOPHILIA A</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, EX23-26DEL
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</div>
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011062" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011062" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011062</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (<a href="/entry/306700">306700</a>) (patient HDX2) and factor VIII inhibitors, <a href="#34" class="mim-tip-reference" title="Din, N., Schwartz, M., Kruse, T., Vestertgaard, S. R., Ahrens, P., Scheibel, E., Nordfang, O., Ezban, M. <strong>Factor VIII gene-specific probes used to study heritage and molecular defects in hemophilia A. (Abstract)</strong> Ric. Clin. Lab. 16: 182 only, 1986."None>Din et al. (1986)</a> found a deletion of exons 23-26 of the factor VIII gene. See also <a href="#74" class="mim-tip-reference" title="Lavergne, J. M., Bahnak, B. R., Vidaud, M., Laurian, Y., Meyer, D. <strong>A directed search for mutations in hemophilia A using restriction enzyme analysis and denaturing gradient gel electrophoresis: a study of seven exons in the factor VIII gene of 170 cases.</strong> Nouv. Rev. Franc. Hemat. 34: 85-91, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1523102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1523102</a>]" pmid="1523102">Lavergne et al. (1992)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1523102" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<a id="0267" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0267 HEMOPHILIA A</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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F8, 1-BP DEL
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2124094327 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2124094327;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2124094327" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2124094327" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011063" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011063" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011063</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p><a href="#38" class="mim-tip-reference" title="Favier, R., Lavergne, J.-M., Costa, J.-M., Caron, C., Mazurier, C., Viemont, M., Delpech, M., Valleix, S. <strong>Unbalanced X-chromosome inactivation with a novel FVIII gene mutation resulting in severe hemophilia A in a female.</strong> Blood 96: 4373-4375, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11110718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11110718</a>]" pmid="11110718">Favier et al. (2000)</a> described a 14-month-old girl with severe hemophilia A (<a href="/entry/306700">306700</a>). Both of her parents had normal values of factor VIII activity, and von Willebrand disease was excluded. Karyotype analysis demonstrated no obvious alteration, and no F8 gene inversions were found. Direct sequencing of the F8 gene exons revealed a frameshift-stop mutation (Q565delC/ter566) in the heterozygous state in the proposita only. F8 gene polymorphism analysis indicated that the mutation must have occurred de novo in the paternal germline. Furthermore, analysis of the pattern of X chromosome methylation at the human androgen receptor gene locus demonstrated a skewed inactivation of the derived maternal X chromosome from the lymphocytes of the proband's DNA. Thus, the severe hemophilia A in the proposita resulted from a de novo F8 gene mutation on the paternally derived X chromosome, associated with a nonrandom pattern of inactivation of the maternally derived X chromosome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11110718" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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F8, CYS179GLY
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852475 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852475;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852475" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852475" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011064" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011064" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011064</a>
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<p>In 2 brothers with severe hemophilia A (<a href="/entry/306700">306700</a>), <a href="#83" class="mim-tip-reference" title="Mazurier, C., Parquet-Gernez, A., Gaucher, C., Lavergne, J.-M., Goudemand, J. <strong>Factor VIII deficiency not induced by FVIII gene mutation in a female first cousin of two brothers with haemophilia A.</strong> Brit. J. Haemat. 119: 390-392, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12406074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12406074</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2002.03819.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12406074">Mazurier et al. (2002)</a> found a T-to-G transversion in exon 4 of the F8C gene, resulting in a cys179-to-gly (C179G) mutation. This mutation affected a cysteine residue in the A1 domain that is conserved in the sequences of the murine, canine, and swine factor 8 genes. A maternal first cousin showed factor VIII deficiency and bleeding, but was found instead to have von Willebrand disease type 2N (see <a href="/entry/613554">613554</a>) due to compound heterozygous mutations in the VWF gene (<a href="/entry/613160#0035">613160.0035</a> and <a href="/entry/613160#0036">613160.0036</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12406074" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0269 HEMOPHILIA A</strong>
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F8, TYR16CYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852476 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852476;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852476" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852476" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011065" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011065" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011065</a>
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<p><a href="#131" class="mim-tip-reference" title="Valleix, S., Vinciguerra, C., Lavergne, J.-M., Leuer, M., Delpech, M., Negrier, C. <strong>Skewed X-chromosome inactivation in monochorionic diamniotic twin sisters results in severe and mild hemophilia A.</strong> Blood 100: 3034-3036, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12351418/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12351418</a>] [<a href="https://doi.org/10.1182/blood-2002-01-0277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12351418">Valleix et al. (2002)</a> described an A-to-G transition in exon 1 of the F8 gene in monozygotic twin females that caused a tyr16-to-cys (Y16C) mutation. Both twins were heterozygous for the mutation, which caused severe hemophilia A (<a href="/entry/306700">306700</a>) in 1 and mild phenotype in the other. The mutation was not present in the twins' healthy sister or parents, suggesting that it had occurred de novo in the germline of 1 parent. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12351418" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0270 HEMOPHILIA A</strong>
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F8, ALU INS
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011066" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011066" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011066</a>
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<p><a href="#124" class="mim-tip-reference" title="Sukarova, E., Dimovski, A. J., Tchacarova, P., Petkov, G. H., Efremov, G. D. <strong>An Alu insert as the cause of a severe form of hemophilia A.</strong> Acta Haemat. 106: 126-129, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11713379/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11713379</a>] [<a href="https://doi.org/10.1159/000046602" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11713379">Sukarova et al. (2001)</a> described a family with a severe form of hemophilia A (<a href="/entry/306700">306700</a>) in which they identified an Alu retrotransposition event in a coding exon, which represented the first report of an Alu insertion in the F8 gene. The propositus was an 18-year-old Bulgarian boy in whom the diagnosis of severe hemophilia had been made at the age of 1 year. His 12-year-old brother was also affected. There was no other family history of the disorder. The 341-bp element incorporated into the F8C gene interrupted the reading frame of the mature protein at met1224, resulting in a stop codon within the inserted sequence. Sequence analysis showed that the inserted fragment was a full Alu repeat belonging to the Yb8 subfamily of Alu repetitive sequences, according to the standardized nomenclature for Alu repeats (<a href="#15" class="mim-tip-reference" title="Batzer, M. A., Deininger, P. L., Hellmann-Blumberg, U., Jurka, J., Labuda, D., Rubin, C. M., Schmid, C. W., Zietkiewicz, E., Zuckerkandl, E. <strong>Standardized nomenclature for Alu repeats.</strong> J. Molec. Evol. 42: 3-6, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8576960/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8576960</a>] [<a href="https://doi.org/10.1007/BF00163204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8576960">Batzer et al., 1996</a>). The mutation site was flanked by a 5-bp (AAGAA) direct repeat which <a href="#124" class="mim-tip-reference" title="Sukarova, E., Dimovski, A. J., Tchacarova, P., Petkov, G. H., Efremov, G. D. <strong>An Alu insert as the cause of a severe form of hemophilia A.</strong> Acta Haemat. 106: 126-129, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11713379/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11713379</a>] [<a href="https://doi.org/10.1159/000046602" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11713379">Sukarova et al. (2001)</a> stated was the shortest direct repeat described at the integration points of Alu insertions. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11713379+8576960" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#42" class="mim-tip-reference" title="Ganguly, A., Dunbar, T., Chen, P., Godmilow, L., Ganguly, T. <strong>Exon skipping caused by an intronic insertion of a young Alu Yb9 element leads to severe hemophilia A.</strong> Hum. Genet. 113: 348-352, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12884004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12884004</a>] [<a href="https://doi.org/10.1007/s00439-003-0986-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12884004">Ganguly et al. (2003)</a> reported a second instance: a 6-year-old male in whom an Alu element was inserted at position -19 of intron 18 of the F8C gene, causing skipping of exon 19 and hemophilia A. The insertion, which did not affect the natural splice donor site, was in the opposite orientation with respect to the direction of transcription of the F8 gene. The size of intron 18 was predicted to be increased by approximately 331 nucleotides because of the insertion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12884004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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F8, 2113+461_2113+473DEL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs781928603 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs781928603;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs781928603?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs781928603" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs781928603" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000591635 OR RCV002248811" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000591635, RCV002248811" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000591635...</a>
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<p>In 2 unrelated probands with mild hemophilia A (HEMA; <a href="/entry/306700">306700</a>), <a href="#67" class="mim-tip-reference" title="Jourdy, Y., Janin, A., Fretigny, M., Lienhart, A., Negrier, C., Bozon, D., Vinciguerra, C. <strong>Recurrent F8 intronic deletion found in mild hemophilia A causes Alu exonization.</strong> Am. J. Hum. Genet. 102: 199-206, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29357978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29357978</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29357978[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2017.12.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29357978">Jourdy et al. (2018)</a> identified an intronic deletion (c.2113+461_2113+473del, NM_000132.3) in intron 13 of the F8 gene. Transcription analysis of patient cells showed an aberrant transcript resulting from this deletion; it caused the insertion of a 122-bp intronic fragment (c.2113_2114ins2113+477_2113+598) at the exon 13-14 junction. This out-of-frame insertion was predicted to result in a truncated protein (Gly705AspfsTer37). DNA sequencing analysis showed that the included pseudoexon corresponds to an antisense AluY element, and that the deletion removed a part of the poly(T)-tail from the right arm of AluY. The findings suggested aberrant exonization of the AluY element that likely resulted from decreased binding of the cryptic exon silencer HNRNPC (<a href="/entry/164020">164020</a>). Disruption of or siRNA-mediated knockdown of HNRNPC in HeLa cells reproduced the effect of the deletion. Screening of 992 unrelated French families with mild hemophilia A found a deletion in the poly(T)-tail of AluY in intron 13 in 6.1% of families, although these resulted from several different intronic deletions in this region, suggesting a recurring molecular mechanism. Haplotype analysis suggested a founder effect for c.2113+461_2113+473del. The patients also carried a normal F8 transcript in addition to the aberrant transcript, explaining the mild phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29357978" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0272 THROMBOPHILIA, X-LINKED, DUE TO FACTOR VIII DEFECT</strong>
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F8, 23.4-KB DUP
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV004560336" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV004560336" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV004560336</a>
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<p>In 7 individuals from 2 Italian families with thrombophilia due to factor VIII defect (THPH13; <a href="/entry/301071">301071</a>), <a href="#123" class="mim-tip-reference" title="Simioni, P., Cagnin, S., Sartorello, F., Sales, G., Pagani, L., Bulato, C., Gavasso, S., Nuzzo, F., Chemello, F., Radu, C. M., Tormene, D., Spiezia, L., Hackeng, T. M., Campello, E., Castoldi, E. <strong>Partial F8 gene duplication (factor VIII Padua) associated with high factor VIII levels and familial thrombophilia.</strong> Blood 137: 2383-2393, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33275657/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33275657</a>] [<a href="https://doi.org/10.1182/blood.2020008168" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33275657">Simioni et al. (2021)</a> identified a 23.4-kb tandem duplication in the F8 gene, including the promoter, exon 1, and part of intron 1. The mutation was hemizygous in affected males and heterozygous in affected females. The mutation was found by a combination of linkage analysis, MLPA analysis, whole-genome sequencing, and Sanger sequencing. The mutation segregated with disease in both families. The variant was not present in the 1000 Genomes Project database or in 103 control individuals. F8 mRNA was increased in patient lymphocytes. Increased transcriptional activity of fragments of the duplicated region was demonstrated via luciferase assay. The authors designated this mutation 'FVIII Padua.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33275657" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#Aly1992" class="mim-tip-reference" title="Aly, A. M., Hoyer, L. W. <strong>Factor VIII-East Hartford (arginine1689 to cysteine) has procoagulant activity when separated from von Willebrand factor.</strong> J. Clin. Invest. 89: 1382-1387, 1992.">Aly et al. (1992)</a>; <a href="#Barrow1973" class="mim-tip-reference" title="Barrow, E. M. S., Graham, J. B. <strong>Factor VIII. (Letter)</strong> Lancet 301: 1312-1313, 1973. Note: Originally Volume I.">Barrow and Graham (1973)</a>; <a href="#Bloom1977" class="mim-tip-reference" title="Bloom, A. L., Peake, I. R. <strong>Molecular genetics of factor VIII and its disorders.</strong> Semin. Hemat. 14: 319-339, 1977.">Bloom and Peake (1977)</a>; <a href="#Gitschier1985" class="mim-tip-reference" title="Gitschier, J., Wood, W. I., Tuddenham, E. G. D., Shuman, M. A., Goralka, T. M., Chen, E. Y., Lawn, R. M. <strong>Detection and sequence of mutations in the factor VIII gene of haemophiliacs.</strong> Nature 315: 427-430, 1985.">Gitschier et al. (1985)</a>; <a href="#Graham1985" class="mim-tip-reference" title="Graham, J. B., Green, P. P., McGraw, R. A., Davis, L. M. <strong>Application of molecular genetics to prenatal diagnosis and carrier detection in the hemophilias: some limitations.</strong> Blood 66: 759-764, 1985.">Graham et al. (1985)</a>; <a href="#Gralnick1976" class="mim-tip-reference" title="Gralnick, H. R., Coller, B. S. <strong>Molecular defects in haemophilia A and von Willebrand's disease.</strong> Lancet 307: 837-838, 1976. Note: Originally Volume I.">Gralnick and Coller
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(1976)</a>; <a href="#Green1991" class="mim-tip-reference" title="Green, P. M., Montandon, A. J., Bentley, D. R., Giannelli, F. <strong>Genetics and molecular biology of haemophilias A and B.</strong> Blood Coagul. Fibrinolysis 2: 539-565, 1991.">Green et al. (1991)</a>; <a href="#Hoyer1981" class="mim-tip-reference" title="Hoyer, L. W. <strong>The factor VIII complex: structure and function.</strong> Blood 58: 1-13, 1981.">Hoyer (1981)</a>; <a href="#Jaffe1975" class="mim-tip-reference" title="Jaffe, E. A., Nachman, R. L. <strong>Subunit structure of factor VIII antigen synthesized by cultured human endothelial cells.</strong> J. Clin. Invest. 56: 698-702, 1975.">Jaffe and Nachman (1975)</a>; <a href="#Janco1987" class="mim-tip-reference" title="Janco, R. L., Phillips, J. A., III, Orlando, P. J., Woodard, M. J., Wion, K. L., Lawn, R. M. <strong>Detection of hemophilia A carriers using intragenic factor VIII:C DNA polymorphisms.</strong> Blood 69: 1539-1541, 1987.">Janco et al. (1987)</a>; <a href="#Lawn1985" class="mim-tip-reference" title="Lawn, R. M. <strong>The molecular genetics of hemophilia: blood clotting factors VIII and IX.</strong> Cell 42: 405-406, 1985.">Lawn (1985)</a>; <a href="#Marchesi1972" class="mim-tip-reference" title="Marchesi, S. L., Shulman, N. R., Gralnick, H. R. <strong>Studies on the purification and characterization of human factor VIII.</strong> J. Clin. Invest. 51: 2151-2161, 1972.">Marchesi et al. (1972)</a>; <a href="#Nilsson1966" class="mim-tip-reference" title="Nilsson, I. M., Blomback, M., Ramgren, O. <strong>Investigations on hemophilia A and B carriers.</strong> Bibl. Haemat. 26: 26-29, 1966.">Nilsson et
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al. (1966)</a>; <a href="#Oberle1985" class="mim-tip-reference" title="Oberle, I., Drayna, D., Camerino, G., White, R., Mandel, J.-L. <strong>The telomeric region of the human X chromosome long arm: presence of a highly polymorphic DNA marker and analysis of recombination frequency.</strong> Proc. Nat. Acad. Sci. 82: 2824-2828, 1985.">Oberle et al. (1985)</a>; <a href="#Peake1985" class="mim-tip-reference" title="Peake, I. R., Lillicrap, D. P., Liddell, M. B., Matthews, R. J., Bloom, A. L. <strong>Linked and intragenic probes for haemophilia A.</strong> Lancet 326: 1003-1004, 1985. Note: Originally Volume II.">Peake et al. (1985)</a>; <a href="#Pratt1999" class="mim-tip-reference" title="Pratt, K. P., Shen, B. W., Takeshima, K., Davie, E. W., Fujikawa, K., Stoddard, B. L. <strong>Structure of the C2 domain of human factor VIII at 1.5 angstrom resolution.</strong> Nature 402: 439-442, 1999.">Pratt et al.
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Abrams, E. S., Murdaugh, S. E., Lerman, L. S.
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<strong>Comprehensive detection of single base changes in human genomic DNA using denaturing gradient gel electrophoresis and a GC clamp.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2387581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2387581</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2387581" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0888-7543(90)90188-z" target="_blank">Full Text</a>]
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Acquila, M., Caprino, D., Pecorara, M., Baudo, F., Morfini, M., Mori, P. G.
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<strong>Two novel mutations at 373 codon of FVIII gene detected by DGGE.</strong>
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Thromb. Haemost. 69: 392-393, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8497853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8497853</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8497853" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Aly, A. M., Arai, M., Hoyer, L. W.
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<strong>Cysteamine enhances the procoagulant activity of factor VIII-East Hartford, a dysfunctional protein due to a light chain thrombin cleavage site mutation (arginine-1689 to cysteine).</strong>
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J. Clin. Invest. 89: 1375-1381, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1569180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1569180</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1569180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI115725" target="_blank">Full Text</a>]
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<a id="Aly1992" class="mim-anchor"></a>
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Aly, A. M., Higuchi, M., Kasper, C. K., Kazazian, H. H., Jr., Antonarakis, S. E., Hoyer, L. W.
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<strong>Hemophilia A due to mutations that create new N-glycosylation sites.</strong>
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Proc. Nat. Acad. Sci. 89: 4933-4937, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1594597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1594597</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1594597" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.89.11.4933" target="_blank">Full Text</a>]
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Aly, A. M., Hoyer, L. W.
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<strong>Factor VIII-East Hartford (arginine1689 to cysteine) has procoagulant activity when separated from von Willebrand factor.</strong>
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J. Clin. Invest. 89: 1382-1387, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1569181/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1569181</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1569181" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI115726" target="_blank">Full Text</a>]
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<a id="Antonarakis1985" class="mim-anchor"></a>
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Antonarakis, S. E., Copeland, K. L., Carpenter, R. J., Jr., Carta, C. A., Hoyer, L. W., Caskey, C. T., Toole, J. J., Kazazian, H. H., Jr.
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<strong>Prenatal diagnosis of haemophilia A by factor VIII gene analysis.</strong>
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Lancet 325: 1407-1409, 1985. Note: Originally Volume I.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2861360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2861360</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2861360" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0140-6736(85)91842-2" target="_blank">Full Text</a>]
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Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D.
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<strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong>
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Hum. Mutat. 5: 1-22, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7728145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7728145</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7728145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.1380050102" target="_blank">Full Text</a>]
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Antonarakis, S. E., Rossiter, J. P., Young, M., Horst, J., de Moerloose, P., Sommer, S. S., Ketterling, R. P., Kazazian, H. H., Jr., Negrier, C., Vinciguerra, C., Gitschier, J., Goossens, M., and 54 others.
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<strong>Factor VIII inversions in severe hemophilia A: results from an international consortium.</strong>
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Blood 86: 2206-2212, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7662970/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7662970</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7662970" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Antonarakis, S. E., Waber, P. G., Kittur, S. D., Patel, A. S., Kazazian, H. H., Jr., Mellis, M. A., Counts, R. B., Stamatoyannopoulos, G., Bowie, E. J. W., Fass, D. N., Pittman, D. D., Wozney, J. M., Toole, J. J.
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<strong>Hemophilia A: detection of molecular defects and of carriers by DNA analysis.</strong>
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New Eng. J. Med. 313: 842-848, 1985.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2993888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2993888</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2993888" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1056/NEJM198510033131402" target="_blank">Full Text</a>]
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Arai, M., Higuchi, M., Antonarakis, S. E., Kazazian, H. H., Jr., Phillips, J. A., III, Janco, R. L., Hoyer, L. W.
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<strong>Characterization of a thrombin cleavage site mutation (arg1689-to-cys) in the factor VIII gene of two unrelated patients with cross-reacting material-positive hemophilia A.</strong>
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Blood 75: 384-389, 1990.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2104766/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2104766</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2104766" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<strong>Direct characterization of factor VIII in plasma: detection of a mutation altering a thrombin cleavage site (arginine372-to-histidine).</strong>
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[<a href="https://doi.org/10.1073/pnas.86.11.4277" target="_blank">Full Text</a>]
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<strong>Toward a physical map of the Xq28 region in man: linking color vision, G6PD, and coagulation factor VIII genes to an X-Y homology region.</strong>
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[<a href="https://doi.org/10.1016/0888-7543(89)90269-3" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00291718" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0140-6736(73)91319-6" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00163204" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00193593" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1365-2141.1989.tb04266.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/3.4.651" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1126/science.111.2896.723" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1365-2141.2008.07310.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1097/00001721-199108000-00007" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.1987.tb03316.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/humu.20345" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.88.19.8307" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.88.16.7405" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0888-7543(90)90448-4" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1056/NEJM199401063300108" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00283686" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00208947" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1172/JCI108140" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12406074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12406074</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12406074" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1046/j.1365-2141.2002.03819.x" target="_blank">Full Text</a>]
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<div class="">
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McGinniss, M. J., Kazazian, H. H., Jr., Hoyer, L. W., Bi, L., Inaba, H., Antonarakis, S. E.
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<strong>Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A.</strong>
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[<a href="https://doi.org/10.1006/geno.1993.1073" target="_blank">Full Text</a>]
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<p class="mim-text-font">
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Migeon, B. R., McGinniss, M. J., Antonarakis, S. E., Axelman, J., Stasiowski, B. A., Youssoufian, H., Kearns, W. G., Chung, A., Pearson, P. L., Kazazian, H. H., Jr., Muneer, R. S.
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<strong>Severe hemophilia A in a female by cryptic translocation: order and orientation of factor VIII within Xq28.</strong>
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Genomics 16: 20-25, 1993. Note: Erratum: Genomics 16: 792 only, 1993.
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[<a href="https://doi.org/10.1006/geno.1993.1134" target="_blank">Full Text</a>]
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<p class="mim-text-font">
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Mikami, S.
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<strong>Gene analysis in haemophilia A--restriction fragment length polymorphism and molecular defects in the factor VIII gene.</strong>
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Millar, D. S., Steinbrecher, R. A., Wieland, K., Grundy, C. B., Martinowitz, U., Krawczak, M., Zoll, B., Whitmore, D., Stephenson, J., Mibashan, R. S., Kakkar, V. V., Cooper, D. N.
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<strong>The molecular genetic analysis of haemophilia A: characterization of six partial deletions in the factor VIII gene.</strong>
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[<a href="https://doi.org/10.1007/BF00197709" target="_blank">Full Text</a>]
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Millar, D. S., Zoll, B., Martinowitz, U., Kakkar, V. V., Cooper, D. N.
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<strong>The molecular genetics of haemophilia A: screening for point mutations in the factor VIII gene using the restriction enzyme TaqI.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1840568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1840568</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1840568" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/BF00209022" target="_blank">Full Text</a>]
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<strong>Classic hemophilia in a female with X/17 complex translocation and partial deletion of the long arm X chromosome (Xq11-13). (Abstract)</strong>
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<strong>Illegitimate recombination produced a duplication within the FVIII gene in a patient with mild hemophilia A.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2159433/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2159433</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2159433" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0888-7543(90)90526-z" target="_blank">Full Text</a>]
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<a id="Myers1985" class="mim-anchor"></a>
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Myers, R. M., Fischer, S. G., Lerman, L. S., Maniatis, T.
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<strong>Nearly all single base substitutions in DNA fragments joined to a GC-clamp can be detected by denaturing gradient gel electrophoresis.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4000972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4000972</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4000972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/nar/13.9.3131" target="_blank">Full Text</a>]
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<a id="92" class="mim-anchor"></a>
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<a id="Myers1985" class="mim-anchor"></a>
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Myers, R. M., Fischer, S. G., Maniatis, T., Lerman, L. S.
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<strong>Modification of the melting properties of duplex DNA by attachment of a GC-rich DNA sequence as determined by denaturing gradient gel electrophoresis.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2987873/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2987873</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2987873" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/nar/13.9.3111" target="_blank">Full Text</a>]
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<a id="Nafa1992" class="mim-anchor"></a>
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<strong>A novel mutation (Arg-to-Leu in exon 18) in factor VIII gene responsible for moderate hemophilia A.</strong>
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Hum. Mutat. 1: 77-78, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301194</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301194" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.1380010114" target="_blank">Full Text</a>]
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</p>
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<strong>Investigation of factor VIIIC gene restriction fragment length polymorphisms and search for deletions in hemophiliac subjects in Algeria.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1969840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1969840</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1969840" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/BF00195808" target="_blank">Full Text</a>]
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</p>
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<a id="Naylor1991" class="mim-anchor"></a>
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<strong>Detection of three novel mutations in two haemophilia A patients by rapid screening of whole essential region of factor VIII gene.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1671991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1671991</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1671991" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0140-6736(91)92450-g" target="_blank">Full Text</a>]
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<a id="96" class="mim-anchor"></a>
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<a id="Naylor1992" class="mim-anchor"></a>
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Naylor, J. A., Green, P. M., Rizza, C. R., Giannelli, F.
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<strong>Factor VIII gene explains all cases of haemophilia A.</strong>
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Lancet 340: 1066-1067, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1357455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1357455</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1357455" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0140-6736(92)93080-7" target="_blank">Full Text</a>]
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<a id="97" class="mim-anchor"></a>
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<a id="Naylor1993" class="mim-anchor"></a>
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Naylor, J. A., Green, P. M., Rizza, C. R., Giannelli, F.
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<strong>Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients.</strong>
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Hum. Molec. Genet. 2: 11-17, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490618</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8490618" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/2.1.11" target="_blank">Full Text</a>]
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<a id="98" class="mim-anchor"></a>
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<a id="Naylor1993" class="mim-anchor"></a>
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Naylor, J., Brinke, A., Hassock, S., Green, P. M., Giannelli, F.
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<strong>Characteristic mRNA abnormality found in half the patients with severe haemophilia A is due to large DNA inversions.</strong>
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Hum. Molec. Genet. 2: 1773-1778, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8281136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8281136</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8281136" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/2.11.1773" target="_blank">Full Text</a>]
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<strong>Purification and characterization of factor VIII 372-cys: a hypofunctional cofactor from a patient with moderately severe hemophilia A.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2109644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2109644</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2109644" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<strong>The telomeric region of the human X chromosome long arm: presence of a highly polymorphic DNA marker and analysis of recombination frequency.</strong>
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[<a href="https://doi.org/10.1073/pnas.82.9.2824" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3932885/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3932885</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3932885" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/317726a0" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="136" class="mim-anchor"></a>
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<a id="Wood1984" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wood, W. I., Capon, D. J., Simonsen, C. C., Eaton, D. L., Gitschier, J., Keyt, B., Seeburg, P. H., Smith, D. H., Hollingshead, P., Wion, K. L., Delwart, E., Tuddenham, E. G. D., Vehar, G. A., Lawn, R. M.
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<strong>Expression of active human factor VIII from recombinant DNA clones.</strong>
|
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Nature 312: 330-337, 1984.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438526</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6438526" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/312330a0" target="_blank">Full Text</a>]
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</p>
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<a id="137" class="mim-anchor"></a>
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<a id="Woods-Samuels1989" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Woods-Samuels, P., Wong, C., Mathias, S. L., Scott, A. F., Kazazian, H. H., Jr., Antonarakis, S. E.
|
|
<strong>Characterization of a nondeleterious L1 insertion in an intron of the human factor VIII gene and further evidence of open reading frames in functional L1 elements.</strong>
|
|
Genomics 4: 290-296, 1989.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2497061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2497061</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2497061" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0888-7543(89)90332-7" target="_blank">Full Text</a>]
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<li>
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<a id="138" class="mim-anchor"></a>
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<a id="Woolf1962" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Woolf, L. I.
|
|
<strong>Gene expression in heterozygotes.</strong>
|
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Nature 194: 609-610, 1962.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14008280/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14008280</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14008280" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/194609a0" target="_blank">Full Text</a>]
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</p>
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<a id="139" class="mim-anchor"></a>
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<a id="Young1997" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Young, M., Inaba, H., Hoyer, L. W., Higuchi, M., Kazazian, H. H., Jr., Antonarakis, S. E.
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<strong>Partial correction of a severe molecular defect in hemophilia A, because of errors during expression of the factor VIII gene.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9042915/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9042915</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9042915" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="140" class="mim-anchor"></a>
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<a id="Youssoufian1987" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Youssoufian, H., Antonarakis, S. E., Aronis, S., Tsiftis, G., Phillips, D. G., Kazazian, H. H., Jr.
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<strong>Characterization of five partial deletions of the factor VIII gene.</strong>
|
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Proc. Nat. Acad. Sci. 84: 3772-3776, 1987.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3035554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3035554</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3035554" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.84.11.3772" target="_blank">Full Text</a>]
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<a id="141" class="mim-anchor"></a>
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<a id="Youssoufian1988" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Youssoufian, H., Antonarakis, S. E., Bell, W., Griffin, A. M., Kazazian, H. H., Jr.
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<strong>Nonsense and missense mutations in hemophilia A: estimate of the relative mutation rate at CG dinucleotides.</strong>
|
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Am. J. Hum. Genet. 42: 718-725, 1988.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2833855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2833855</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2833855" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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<a id="142" class="mim-anchor"></a>
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<a id="Youssoufian1987" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Youssoufian, H., Antonarakis, S. E., Kasper, C. K., Phillips, D. G., Kazazian, H. H., Jr.
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<strong>The spectrum and origin of mutations in hemophilia A. (Abstract)</strong>
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Am. J. Hum. Genet. 41: A249 only, 1987.
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<li>
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<a id="143" class="mim-anchor"></a>
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<a id="Youssoufian1988" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Youssoufian, H., Kasper, C. K., Phillips, D. G., Kazazian, H. H., Jr., Antonarakis, S. E.
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<strong>Restriction endonuclease mapping of six novel deletions of the factor VIII gene in hemophilia A.</strong>
|
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Hum. Genet. 80: 143-148, 1988.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3139545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3139545</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3139545" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/BF00702857" target="_blank">Full Text</a>]
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<li>
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<a id="144" class="mim-anchor"></a>
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<a id="Youssoufian1986" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Youssoufian, H., Kazazian, H. H., Jr., Phillips, D. G., Aronis, S., Tsiftis, G., Brown, V. A., Antonarakis, S. E.
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<strong>Recurrent mutations in haemophilia A give evidence for CpG mutation hotspots.</strong>
|
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Nature 324: 380-382, 1986.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3097553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3097553</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3097553" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/324380a0" target="_blank">Full Text</a>]
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<li>
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<a id="145" class="mim-anchor"></a>
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<a id="Youssoufian1988" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Youssoufian, H., Wong, C., Aronis, S., Platokoukis, H., Kazazian, H. H., Jr., Antonarakis, S. E.
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<strong>Moderately severe hemophilia A resulting from glu-to-gly substitution in exon 7 of the factor VIII gene.</strong>
|
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Am. J. Hum. Genet. 42: 867-871, 1988.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2835904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2835904</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2835904" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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<li>
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<a id="146" class="mim-anchor"></a>
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<a id="Zacharski1968" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zacharski, L. R., Bowie, E. J. W., Titus, J. L., Owen, C. A., Jr.
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<strong>Synthesis of antihemophilic factor (factor VIII) by leukocytes: preliminary report.</strong>
|
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Mayo Clin. Proc. 43: 617-619, 1968.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5751674/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5751674</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5751674" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</ol>
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<br />
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</div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 02/25/2022
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</span>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 03/23/2018<br>Patricia A. Hartz - updated : 11/1/2011
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<a id="creationDate" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin : 4/5/2011
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 07/09/2024
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<div class="row collapse" id="mimCollapseEditHistory">
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<span class="mim-text-font">
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carol : 08/14/2023<br>carol : 08/07/2023<br>carol : 07/25/2023<br>carol : 03/30/2022<br>carol : 03/11/2022<br>carol : 02/25/2022<br>carol : 02/22/2022<br>alopez : 01/04/2022<br>mgross : 05/12/2021<br>alopez : 03/27/2018<br>ckniffin : 03/23/2018<br>carol : 08/11/2016<br>carol : 07/15/2016<br>carol : 6/24/2016<br>carol : 3/15/2016<br>carol : 3/14/2016<br>carol : 1/30/2016<br>carol : 11/30/2015<br>carol : 11/17/2015<br>carol : 11/16/2015<br>carol : 11/16/2015<br>terry : 9/14/2012<br>carol : 5/30/2012<br>terry : 4/12/2012<br>mgross : 11/13/2011<br>terry : 11/1/2011<br>terry : 6/24/2011<br>terry : 6/24/2011<br>terry : 6/23/2011<br>terry : 6/23/2011<br>terry : 6/23/2011<br>terry : 4/13/2011<br>carol : 4/8/2011<br>terry : 4/8/2011<br>carol : 4/7/2011<br>ckniffin : 4/6/2011
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<h3>
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<span class="mim-font">
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<strong>*</strong> 300841
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<div>
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<h3>
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<span class="mim-font">
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COAGULATION FACTOR VIII; F8
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</span>
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</h3>
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<div>
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<br />
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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FACTOR VIII<br />
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COAGULATION FACTOR VIIIC, PROCOAGULANT COMPONENT; F8C
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</span>
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</h4>
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</div>
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<div>
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<br />
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: F8</em></strong>
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</span>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 16872008, 26029002, 28293008;
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<strong>ICD10CM:</strong> D66;
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<strong>ICD9CM:</strong> 286.0;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: Xq28
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Genomic coordinates <span class="small">(GRCh38)</span> : X:154,835,792-155,022,723 </span>
|
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</em>
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</strong>
|
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<span class="small">(from NCBI)</span>
|
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="2">
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<span class="mim-font">
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Xq28
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</span>
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</td>
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<td>
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<span class="mim-font">
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Hemophilia A
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</span>
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</td>
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<td>
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<span class="mim-font">
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306700
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</span>
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</td>
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<td>
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<span class="mim-font">
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X-linked recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Thrombophilia 13, X-linked, due to factor VIII defect
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</span>
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</td>
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<td>
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<span class="mim-font">
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301071
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</span>
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</td>
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<td>
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<span class="mim-font">
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The F8 gene encodes coagulation factor VIII, a large plasma glycoprotein that functions in the blood coagulation cascade as a cofactor for the factor IXa (300746)-dependent activation of factor X (F10; 613872). Factor VIII is activated proteolytically by a variety of coagulation enzymes, including thrombin (F2; 176930). Factor VIII is tightly associated in the blood with von Willebrand factor (VWF; 613160), which serves as a protective carrier protein for factor VIII (summary by Toole et al., 1984; review by Hoyer, 1994). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Fay et al. (1982) isolated a highly purified human factor VIII that consisted of a single high molecular weight polypeptide chain having the highest specific activity. </p><p>Toole et al. (1984) isolated clones corresponding to the F8 gene from a human cDNA library. Independently and simultaneously, Gitschier et al. (1984) and Wood et al. (1984) also cloned and expressed the F8 gene. The deduced precursor protein has 2,351 amino acids and a molecular mass of 267 kD. The leader sequence of the proprotein contains 19 amino acids, yielding a mature protein of 2,332 amino acids. The protein has an obvious domain structure, contains sequence repeats, and is structurally related to factor V (F5; 612309) and ceruloplasmin (CP; 117700). F8 has 3 copies of an A domain of 330 to 380 amino acids, a B domain of about 925 amino acids, and 2 C domains of about 160 amino acids. The domains are arranged A1-A2-B-A3-C1-C2. Both A and C repeats show conservation of cysteines, and the B region contains most potential N-glycosylation sites. Northern blot analysis detected a 9-kb F8 transcript. </p><p>The F8 gene is expressed in human liver, spleen, lymph nodes, and a variety of other tissues, but not in bone marrow, peripheral blood lymphocytes, or endothelial cells (Wion et al., 1985). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The F8 gene contains 26 exons and spans 186 kb (Gitschier et al., 1984). </p><p>Levinson et al. (1990) found a curious example of a gene within a gene. In looking for transcripts from the Xq28 region, they found one referred to as the A gene that hybridized to a region in exon 22 of the F8 gene. The A or F8A gene (305423) was in reverse orientation to F8 and was contained entirely in intron 22. Computer analysis of the sequence suggested that the A gene encodes a protein, with the complication that codon usage analysis suggested a frameshift halfway through the gene. The A gene cDNA also bound to mouse, monkey, and rat genomic DNA in a 'zoo blot.' The mouse A gene was also found to be on the X chromosome but not within the mouse F8 gene as it is in the human. </p><p>Freije and Schlessinger (1992) demonstrated that the X chromosome contains 3 copies of F8A and its adjacent regions, 1 in intron 22 and 2 telomeric and upstream to the F8 gene transcription start site. Gene F8A, which is transcribed in the opposite direction to F8, is intronless and completely nested within intron 22. Approximately 500 kb upstream of the F8 gene, there are 2 additional transcribed copies of the F8A gene. Lakich et al. (1993) pointed out that intron 22 is unusual in many respects. At 32 kb, it is the largest intron in the F8 gene. It also contains a CpG island, located about 10 kb downstream of exon 22. This island appears to serve as a bidirectional promoter for the F8A and F8B (305424) genes. The F8B gene is also located in intron 22 and is transcribed in the opposite direction from F8A; its first exon lies within intron 22 and is spliced to exons 23-26. The F8A and B genes are both expressed ubiquitously. </p><p>Having previously reported the existence of 5 CpG islands close to the F8 gene, 4 of which they cloned by genomic walking, Gitschier's group (Kenwrick et al., 1992) reported the isolation of the remaining island, located approximately 70 kb telomeric of the 5-prime end of the F8 gene. They identified cDNA clones corresponding to 2 transcribed sequences, C6.1A (BRCC3; 300617) and C6.1B (MTCP1; 300116), that originate from this CpG island. The C6.1A gene was highly conserved between species and expressed abundantly in many human and mouse tissues. No striking homologies to existing genes could be found for either sequence. Kenwrick et al. (1992) found that both genes were deleted in 2 brothers who suffered from mental handicap and dysmorphism as well as hemophilia A (306700). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By in situ hybridization, Tantravahi et al. (1986) concluded that the F8 gene is located in the proximal part of chromosome Xq28 with probes DX13 and St14 distally located. Using a hybrid cell line that contains only a terminal Xq28 fragment, Tantravahi et al. (1986) found that F8 probes did not hybridize but the DX13 and St14 did hybridize to the DNA of that cell line. </p><p>Patterson et al. (1987) showed that the G6PD (305900) and F8 genes lie within 500 kb of each other. Arveiler et al. (1989) showed that G6PD and F8 are in the same 290-kb pulsed field gel electrophoresis fragment, but did not establish which of the genes is more proximal. </p><p>Kenwrick and Gitschier (1989) established the order: cen--R/GCP--GDX--G6PD--F8--DXS15--tel. The direction of transcription of the GDX, G6PD, and F8 genes is toward the centromere, i.e., the R/GCP end of the region. Patterson et al. (1989) showed that the genomic sequences recognized by the anonymous probe 767 (DXS115) are localized to 2 sites within Xq28. One site lies within intron 22 of the F8 gene. The second site, which contains the RFLPs detected by 767, is located within 1.2 megabases of the F8 gene. Genetic data indicate tight linkage of F8 and DXS115; maximum lod = 8.30 at theta = 0.04. </p><p>G6PD (305900) is one of the 5 rather tightly linked loci located on Xq28, the others being CBD (303800), CBP (303900), HEMA, and ALD (300371). In a physical map of the most distal 12 Mb of Xq, Poustka et al. (1991) found that the F8 gene lies about 1.1 Mb from the telomere, with G6PD proximal to it, and about 1.5 Mb from the telomere. This contradicted the earlier impression that the gene is located in the proximal part of Xq28. </p><p>In a 9-year-old Malaysian female with de novo hemophilia A (306700) as well as a complex de novo translocation involving one X chromosome and one chromosome 17 (Muneer et al., 1986), Migeon et al. (1993) identified a breakpoint within Xq28 with deletion of the 5-prime end of the factor VIII gene, leaving the more proximal G6PD locus intact on the derivative chromosome 17. As the deleted segment included the 5-prime half of F8C as well as the subtelomeric DXYS64 locus, they concluded that F8 is oriented on the chromosome with its 5-prime region closest to the telomere. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Biochemical Features</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Factor VII is a complex of a large inert carrier protein (VWF; 613160) and a noncovalently bound small fragment which contains the procoagulant active site. Zacharski et al. (1968) showed that leukocytes synthesize some factor VIII in vitro; however, it is synthesized primarily in the liver. </p><p>Cooper and Wagner (1974) presented evidence that the carrier molecule is normally present in the plasma of hemophilia A patients. </p><p>Fay et al. (1982) isolated a highly purified human factor VIII that consisted of a single high molecular weight polypeptide chain having the highest specific activity. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Ratnoff and Bennett (1973) reviewed the genetics of hereditary disorders of blood coagulation. </p><p><strong><em>Hemophilia A</em></strong></p><p>
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|
Gitschier et al. (1985) identified truncating mutations in the F8 gene (see, e.g., 300841.0001-300841.0003) as the basis for hemophilia A (306700). A severe hemophiliac with no detectable factor VIIIC activity had an R2307X mutation (300841.0001). Gitschier et al. (1986) found that the same codon was converted to glutamine (R2307Q; 300841.0042) in a mild hemophiliac with 10% of normal activity. A diminished level of factor VIII Ag in the latter patient coincided with the level of clotting activity, suggesting that the abnormal factor VIII was relatively unstable. </p><p>In a study of 83 patients with hemophilia A, Youssoufian et al. (1986) identified 2 different point mutations, one in exon 18 and one in exon 22, that recurred independently in unrelated families. Each mutation produced a nonsense codon by a change of CG to TG. In the opinion of Youssoufian et al. (1986), these observations indicated that CpG dinucleotides are mutation hotspots. It had been postulated that methylated cytosines may be mutation hotspots because 5-methylcytosine can spontaneously deaminate to thymine, resulting in a C-to-T transition in DNA. </p><p>Levinson et al. (1987) used RNAse A cleavage and DNA sequencing of the altered region to identify a mutation in the F8 gene in a patient with hemophilia. The mutation was a novel G-to-C transversion which resulted in a missense mutation, with proline being substituted for arginine in one of the active domains of the factor VIII molecule. </p><p>Youssoufian et al. (1987) characterized 5 different partial deletions of the F8 gene in 83 patients with hemophilia. None had developed circulating inhibitors. One of the deletions occurred de novo in a germ cell of the maternal grandmother, while a second deletion occurred in a germ cell of a maternal grandfather. The findings indicated that de novo deletions of X-linked genes can occur in either male or female gametes. Youssoufian et al. (1988) reported 6 other partial F8 gene deletions in severe hemophilia A, bringing to 12 the number of deletions among 240 patients. No association was observed between the size or location of deletions and the presence of inhibitors to factor VIII. Furthermore, no 'hotspots' for deletion breakpoints were identified. </p><p>Youssoufian et al. (1988) screened 240 patients with hemophilia A and found CG to TG transitions in an exon in 9. They identified novel missense mutations leading to severe hemophilia A and estimated that the extent of hypermutability of CpG dinucleotides is 10 to 20 times greater than the average mutation rate for hemophilia A. </p><p>Cooper and Youssoufian (1988) collated reports of single basepair mutations within gene coding regions causing human genetic disease. They found that 35% of mutations occurred within CpG dinucleotides. Over 90% of these mutations were C-to-T or G-to-A transitions, which thus occur within coding regions at a frequency 42-times higher than that predicted from random mutation. Cooper and Youssoufian (1988) believed these findings were consistent with methylation-induced deamination of 5-methylcytosine and suggested that methylation of DNA within coding regions may contribute significantly to the incidence of human genetic disease. </p><p>Higuchi et al. (1988) found deletion of about 2,000 bases spanning exon 3 and part of IVS3 of the F8 gene in a patient with severe hemophilia A. The mother was judged to be a somatic mosaic because the defective gene could be identified in only a portion of the leukocytes and cultured fibroblasts. </p><p>By use of a cDNA probe corresponding to exons 14-26 of F8, Bardoni et al. (1988) studied 49 Italian patients with severe hemophilia A. They found no TaqI site mutations, but did find a partial deletion, eliminating exons 15-18 and spanning about 13 kb (300841.0046), in a patient with anti-factor VIII antibodies. </p><p>In a case of hemophilia A, Kazazian et al. (1988) described the first instance of insertional mutagenesis in man caused by a long inserted element (LINE) in the F8 gene. L1 (LINE-1) sequences are a human-specific family of long, interspersed, repetitive elements, present in about 100,000 copies dispersed throughout the genome. The full-length L1 sequence is 6.1 kilobases, but most L1 elements are truncated at the 5-prime end, resulting in a 5-fold higher copy number of 3-prime sequences. Kazazian et al. (1988) found insertions of L1 elements into exon 14 of the F8 gene in 2 of 240 unrelated patients with hemophilia A. Both of these insertions (3.8 and 2.3 kb, respectively) contained 3-prime portions of the L1 sequence. They interpreted these results as indicating that certain L1 sequences in man can be dispersed, presumably by an RNA intermediate, and cause disease by insertional mutation. Both of the above insertions were de novo events, appearing either during embryogenesis in the patient or in the mother's germ cells. The L1 element transposed into one of these patients was demonstrated by Dombroski et al. (1991) to have come from a retrotransposable element located on chromosome 22 (see 151626). </p><p>Woods-Samuels et al. (1989) characterized a third L1 insertion in intron 10 of the F8 gene of a hemophilia A patient. This L1 insertion was not a cause of hemophilia in the patient because it was also present in the maternal grandfather, who did not have the disease. Altogether the L1 insertion was present in 4 generations of the family. All 3 of the L1 insertions discovered by Dombroski et al. (1991) have open reading frames (ORFs), and the 3 derived amino acid sequences are 98 to 99% identical. They show similarity in the sequence of the L1 3-prime ORFs, and the polymerase domain of reverse transcriptase was observed in all 3 L1 insertions. The presence of ORFs and the close sequence similarity of these recently inserted L1 elements provide indirect evidence for the existence of a set of functional L1 elements that encodes 1 or more proteins necessary for their retrotransposition. </p><p>In studies of 83 unrelated Finnish patients with hemophilia A, Levinson et al. (1990) identified specific mutations, falling into 3 classes, in 10 patients: 5 mutations caused loss of TaqI restriction sites; 1 point mutation resulted in a new TaqI site; and 4 represented partial gene deletions. Although exons 5 and 6 were involved in 3 of the 4 partial gene deletions, the extent of the DNA loss differed in each. The fourth deletion was located entirely within intron 1. There was no history of hemophilia in 8 of the 10 families. The origin of the mutation was determined in 6 of these pedigrees, 2 of which showed evidence for maternal mosaicism. </p><p>Brocker-Vriends et al. (1990) described a case of hemophilia A due to partial deletion of the F8 gene of about 2 kb, spanning exon 5 and part of introns 4 and 5; the mother was a somatic and presumably gonadal mosaic for the mutation although coagulation assays and RFLP analysis in the family did not suggest a carrier status. </p><p>McGinniss et al. (1993) reported that half of hemophilia A patients have no detectable factor VIII; about 5% have normal levels of dysfunctional factor VIII as protein and are termed CRM-+, whereas the rest ( 45%) have plasma factor VIII Ag protein reduced to an extent roughly comparable to the level of factor VIIIC activity and are designated CRM-reduced. They found in an analysis of mutations that almost all CRM-positive/reduced mutations (24/26) were missense, and many (12/26) occurred at CpG dinucleotides. They showed that 18 of 19 amino acid residues altered by mutation in these patients were conserved in the porcine and murine sequences. Almost half of the mutations (11/26) were clustered in the A2 domain. </p><p>In a review, Antonarakis et al. (1995) collected the findings of more than 1,000 hemophilia subjects examined for F8 gene mutations. These include point mutations, inversions, deletions, and unidentified mutations which constitute 46%, 42%, 8%, 4%, and 91%, 0%, 0%, and 9%, respectively, of those with severe versus mild to moderate disease, respectively, in selected studies. The 266 point mutations described as of April, 1994 comprised missense (53%), CpG-to-TpG (16%), small deletions (12%), nonsense (9%), small inversions and splicing (3% each), and missense polymorphisms and silent mutations in exons (2% each). In addition to these point mutations 100 different larger deletions and 9 insertion mutations had been reported. </p><p>In a study of 147 sporadic cases of severe hemophilia A, Becker et al. (1996) were able to identify the causative defect in the F8 gene in 126 patients (85.7%). An inversion of the gene was found in 55 patients (37.4%), a point mutation in 47 (32%), a small deletion in 14 (9.5%), a large deletion in 8 (5.4%), and a small insertion in 2 (1.4%). In 4 (2.7%), mutations were localized but not yet sequenced. No mutation was identified in 17 patients (11.6%). The identified mutations occurred in the B domain in 16 (10.9%); 4 of these were located in an adenosine nucleotide stretch at codon 1192, indicating a mutation hotspot. Somatic mosaicism was detected in 3 (3.9%) of 76 patients' mothers, comprising 3 of 16 de novo mutations in the patients' mothers. Investigation of family relatives allowed detection of a de novo mutation in 16 of 76 2-generation and 28 of 34 3-generation families. On the basis of these data, Becker et al. (1996) estimated the male:female ratio of mutation frequencies (k) to be 3.6. By use of the quotients of mutation origin in maternal grandfather to patients' mother or to maternal grandmother, k values were directly estimated as 15 and 7.5, respectively. Considering each mutation type separately, they found a mutation type-specific sex ratio of mutation frequencies. Point mutations showed a 5-to-10-fold-higher and inversions a more than 10-fold-higher mutation rate in male germ cells, whereas deletions showed a more than 5-fold-higher mutation rate in female germ cells. Consequently, and in accordance with the data of other disorders such as Duchenne muscular dystrophy, the results indicated to Becker et al. (1996) that at least for X-chromosomal disorders the male:female mutation rate is determined by its proportion of the different mutation types. </p><p>The molecular diagnosis of hemophilia A is challenging because of the high number of different causative mutations that are distributed through the large F8 gene. The putative role of the novel mutations, especially missense mutations, may be difficult to interpret as causing hemophilia A. Guillet et al. (2006) identified 95 novel mutations out of 180 different mutations found among 515 patients with hemophilia A from 406 unrelated families followed up at a single hemophilia treatment center in a Paris hospital. The 95 novel mutations comprised 55 missense mutations, 12 nonsense mutations, 11 splice site mutations, and 17 small insertions/deletions. They used a strategy in interpreting the causality of novel F8 mutations based on a combination of the familial segregation of the mutation, the resulting biologic and clinical hemophilia A phenotype, and the molecular consequences of the amino acid substitution. For the latter, they studied the putative biochemical modifications: its conservation status with cross-species factor VIII and homologous proteins, its putative location in known factor VIII functional regions, and its spatial position in the available factor VIII 3D structures. </p><p>Among 1,410 Italian patients with hemophilia A, Santacroce et al. (2008) identified 382 different mutations in the F8 gene, 217 (57%) of which had not previously been reported. Mutations leading to a null allele accounted for 82%, 15%, and less than 1% of severe, moderate, or mild hemophilia, respectively. Missense mutations were identified in 16%, 68%, and 81% of severe, moderate, or mild hemophilia, respectively, yielding a good genotype/phenotype correlation useful for treatment and genetic counseling. </p><p>To establish a national database of F8 mutations, Green et al. (2008) identified and cataloged multiple mutations in approximately one-third of the U.K. hemophilia A population. The risk of developing inhibitors for patients with nonsense mutations was greater when the stop codon was in the 3-prime half of the mRNA. The most common change was the intron 22 inversion (300841.0067), which accounted for 16.6% of all mutations and for 38% of those causing severe disease. </p><p><strong><em>Inversion Mutations in Intron 22 of the F8 Gene</em></strong></p><p>
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Intron 22 of the human F8 gene is hypomethylated on the active X and methylated on the inactive X. Inaba et al. (1990) described an MspI RFLP in intron 22 of the F8 gene. Japanese showed 45% heterozygosity and Asian Indians showed 13%; polymorphism was not found in American blacks or Caucasians. </p><p>Naylor et al. (1992) found an unusual cluster of mutations involving regions of intron 22 not examined earlier and leading to defective joining of exons 22 and 23 in the mRNA (300841.0067) as the cause of hemophilia A in 10 of 24 severely affected UK patients. These results confirmed predictions about the efficacy of the mRNA-based method suggested by Naylor et al. (1991), and also excluded hypotheses proposing that mutations outside the F8 gene are responsible for a large proportion of severe hemophilia A. </p><p>Of the 28 patients reported by Naylor et al. (1993), 5 had mild or moderate disease and all had a missense mutation. The other 23 patients were severely affected; unexpectedly, intron 22 seemed to be the target of approximately 40% of the mutations causing severe hemophilia A. Naylor et al. (1993) found that the basis of the unique F8 mRNA defect that prevented PCR amplification across the boundary between exons 22 and 23 was an abnormality in the internal regions of intron 22. They showed that exons 1-22 of the F8 mRNA had become part of a hybrid message containing new multiexonic sequences expressed in normal cells. The novel sequences were not located in a YAC containing the whole F8 gene. Southern blots from patients probed by novel sequences and clones covering intron 22 showed no obvious abnormalities. Naylor et al. (1993) also suggested that inversions involving intron 22 repeated sequences are the basis of the mRNA defect. These mutations in severely affected patients occur at the surprising rate of approximately 4 x 10(-6) per gene per gamete per generation. Furthermore, it has been shown that these de novo inversions occur more frequently in males than females with a ratio of 302:1 estimated in male:female germ cells. </p><p>The F8A gene (305423) is contained entirely within intron 22 of the F8 gene and is transcript in the reverse orientation from the F8 gene (Levinson et al., 1990). Lakich et al. (1993) proposed that many of the previously unidentified mutations resulting in severe hemophilia A are based on recombination between the homologous F8A sequences within intron 22 and upstream of the F8 gene. Such a recombination would lead to an inversion of all intervening DNA and a disruption of the gene. Lakich et al. (1993) presented evidence to support this model and described a Southern blot assay that detects the inversion. They suggested that this assay should permit genetic prediction of hemophilia A in approximately 45% of families with severe disease. </p><p>Rossiter et al. (1994) hypothesized that pairing of Xq with its homolog inhibits the intrachromosomal inversion that is responsible for nearly half of all cases of severe hemophilia A. This would predict that the event originates predominantly in male germ cells. They presented findings supporting the hypothesis: in all 20 informative cases in which the inversion originated in a maternal grandparent, DNA polymorphism analysis determined that it occurred in the male germline. In addition, all but 1 of 50 mothers of sporadic cases due to an inversion were carriers. </p><p>Inversion mutations resulting from recombinations between DNA sequences in the A gene in intron 22 of the F8 gene and 1 of 2 other A genes upstream to F8 have been shown to cause a large portion of cases. From data on more than 2,000 samples, Antonarakis et al. (1995) concluded that the common inversion mutations are found in 42% of all severe hemophilia A subjects. Whereas 98% of the mothers of those with inversions were carriers of the inversion, only about 1 de novo inversion was found in maternal cells for every 25 mothers of sporadic cases. When the maternal grandparental origin of inversions was examined the ratio of de novo occurrences in male:female germ cells was 69:1. </p><p>Brinke et al. (1996) reported the presence of a novel inversion in 2 hemophilic monozygotic twins. These patients showed an inversion that affects the first intron of the F8 gene, displacing the most telomeric exon (exon 1) of F8 further towards the telomere and close to the C6.1A gene (BRCC3; 300617). Brinke et al. (1996) noted that this novel inversion creates 2 hybrid transcription units. One of these is formed by the promoter and first exon of F8 and widely expressed sequences that map telomeric to the C6.1A sequence. The other hybrid transcription unit contains the CpG island and all of the known sequence of C6.1A and the 3-prime section of most of the F8 gene. </p><p>It is hypothesized that the inversion mutations occur almost exclusively in germ cells during meiotic cell division by an intrachromosomal recombination between a 9.6-kb sequence within intron 22 and 1 of 2 almost identical copies located about 300 kb distal to the F8 gene at the telomeric end of the X chromosome. Most inversion mutations originate in male germ cells, where the lack of bivalent formation may facilitate flipping of the telomeric end of the single X chromosome. Oldenburg et al. (2000) reported the first instance of intron 22 inversion presenting as somatic mosaicism in a female, affecting only about 50% of lymphocyte and fibroblast cells of the proposita. Supposing a postzygotic de novo mutation as the usual cause of somatic mosaicism, the finding implies that the intron 22 inversion mutation is not restricted to meiotic cell divisions but can also occur during mitotic cell divisions, either in germ cell precursors or in somatic cells. </p><p><strong><em>Hemophilia A with Inhibitors</em></strong></p><p>
|
|
Approximately 10 to 20% of patients with severe hemophilia A develop antibodies, known as inhibitors, to factor VIII following treatment with exogenous factor VIII. Most of these patients have nonsense mutations or deletions in the F8 gene (Antonarakis et al., 1995). </p><p>Antonarakis et al. (1985) identified several molecular defects in families with hemophilia A. One family had a deletion of about 80 kb in the F8 gene, whereas another had a single nucleotide change in the coding region of the gene, resulting in a nonsense codon and premature termination. In addition, they used 2 common polymorphic sites in the F8 gene to differentiate the normal gene from the defective gene in 4 of 6 obligate carriers from families with patients in whom inhibitors did not develop. In both the family with a large deletion and the family with premature termination, affected persons developed inhibitors. </p><p>A variety of F8 gene mutations have been found in patients with hemophilia A due to inhibitors. Among 30 such cases, Antonarakis et al. (1995) found that 87 and 13% had different nonsense and missense mutations, respectively. F8 gene inversions do not seem to be a major predisposing factor for the development of inhibitors. Among severe hemophilia A cases, 16% of those without inversions and 20% of those with inversions developed inhibitors. </p><p>Schwaab et al. (1995) found that the probability of developing factor VIII inhibitors is greater in patients with large deletions in the F8 gene. </p><p>Viel et al. (2009) sequenced the F8 gene in 78 black patients with hemophilia to identify the causative mutations and background haplotypes, which the authors designated H1 to H5. They found that 24% of the patients had an H3 or H4 haplotype, and that the prevalence of inhibitors was higher among patients with either of those haplotypes than among patients with haplotypes H1 or H2 (odds ratio, 3.6; p = 0.04), despite a similar spectrum of hemophilic mutations and degree of severity of illness in the 2 subgroups. Noting that Caucasians carry only the H1 or H2 haplotypes and that most blood donors are Caucasian, Viel et al. (2009) suggested that mismatched factor VIII replacement therapy might be a risk factor for the development of anti-factor VIII alloantibodies. </p><p><strong><em>Thrombophilia, X-Linked, due to Factor VIII Defect</em></strong></p><p>
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|
Shen et al. (2013) evaluated F8 activity and F8 gene copy number in 179 patients with venous thromboembolism and 176 healthy controls. Patients with venous thromboembolism had significantly higher F8 activity compared to controls and also had a significantly greater number of copies of the F8 gene. F8 activity was also correlated to F8 gene copy number in patients versus controls, although this was not true for every individual patient. The F8 copy number was significantly higher in males compared to females. </p><p>In 7 individuals from 2 Italian families with thrombophilia (THPH13; 301071), Simioni et al. (2021) identified a tandem duplication in the factor VIII gene (300841.0272). The 2 families shared a 3-Mb haplotype, indicating a shared common ancestor. F8 mRNA was increased in patient lymphocytes. Increased transcriptional activity of fragments of the duplicated region was demonstrated by luciferase assay and was highest in a region (region C) that overlapped a major DNase I hypersensitivity cluster. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Genotype/Phenotype Correlations</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In a Japanese family with mild to moderately severe hemophilia A, Young et al. (1997) found a deletion of a single nucleotide T within an A(8)TA(2) sequence of exon 14 of the F8 gene. The severity of the clinical phenotype did not correspond to that expected of a frameshift mutation. A small amount of functional factor VIII protein was detected in the patient's plasma. Analysis of DNA and RNA molecules from normal and affected individuals and in vitro transcription/translation suggested a partial correction of the molecular defect, because of the following: (i) DNA replication/RNA transcription errors resulted in restoration of the reading frame and/or (ii) 'ribosomal frameshifting' resulted in the production of normal factor VIII polypeptide and, thus, in a milder-than-expected hemophilia A. All of these mechanisms probably were promoted by the longer run of adenines, A(10) instead of A(8)TA(2), after the deleted T. Young et al. (1997) concluded that errors in the complex steps of gene expression therefore may partially correct a severe frameshift defect and ameliorate an expected severe phenotype. </p><p>Cutler et al. (2002) identified 81 mutations in the F8C gene in 96 unrelated patients, all of whom had previously typed negative for the common IVS22 inversion mutation (300841.0067). Forty-one of these mutations were not recorded in F8C gene mutation databases. Analysis of these 41 mutations with regard to location, possible cross-species conservation, and type of substitution, in correlation with the clinical severity of the disease, supported the view that the phenotypic result of a mutation in the F8C gene correlates more with the position of the amino acid change within the 3-dimensional structure of the protein than with the actual nature of the alteration. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>History</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Early Mutation Detection Methods</em></strong></p><p>
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Since point mutations in the F8 gene are responsible for most cases of hemophilia A and only a small proportion of these mutations could be recognized by restriction endonuclease analysis, Traystman et al. (1990) used PCR and denaturing gradient gel electrophoresis (DGGE) to characterize single nucleotide substitutions. A GC clamp was attached to the 5-prime PCR primer to allow detection of most single base changes in DNA fragments ranging in size from 249 to 356 bp. (A 'GC clamp' is a sequence rich in G and C such that it is relatively resistant to melting by heating; see Myers et al. (1985, 1985) and Abrams et al., 1990.) Ten of 11 known point mutations were definitively separated. Traystman et al. (1990) then used these methods, applied to exon 8, the 3-prime end of exon 14, exon 17, exon 18, and exon 24, in a study of 52 patients with unknown mutations. A 'new' disease-producing mutation was found in 2 of the patients: a missense mutation in exon 14 (tyr1709-to-cys and asn1922-to-asp). A previously described mutation in exon 24 (arg2209-to-gln) In addition, a new polymorphic nucleotide substitution was found in intron 7. Traystman et al. (1990) detected all of these mutations when the GC-clamped products from all 5 regions were run in the same denaturing gel. </p><p>Kogan and Gitschier (1990) likewise used DGGE to identify mutations and found a DNA polymorphism, located in intron 7, which they thought might be useful for genetic prediction in cases in which the BclI and XbaI polymorphisms are uninformative. </p><p>Higuchi et al. (1991) pointed out that whereas nearly all mutations resulting in mild to moderate hemophilia B could be detected by PCR and DGGE, these methods sufficed in only 16 of 30 (53%) patients with severe hemophilia A. They interpreted this to indicate that the mutations in DNA sequence lay outside the regions studied and may include locus-controlling regions, other sequences within introns or outside the gene that are important for its expression, or perhaps another gene involved in factor VIII expression that is very closely linked to the F8 gene. Higuchi et al. (1991) designed a total of 45 primer sets to amplify 99% of the coding region of the F8C gene and 41 of 50 splice junctions. After PCR amplification they used denaturing gradient gel electrophoresis (DGGE) to identify successfully the point mutations in 26 DNAs with different previously identified changes. Among 29 patients with unknown mutations, they identified the disease-producing change in 25 (86%). Two polymorphisms and 2 rare normal variants were also found. </p><p>Naylor et al. (1992) used an mRNA-based method to examine hemophilia A mutations and were able to explain the report of Higuchi et al. (1991) that mutations could not be identified in 14 of 30 severely affected patients, although mutations were found in all but 1 of 17 less severely affected patients. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>272 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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F8, ARG2307TER
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<br />
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SNP: rs137852354,
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ClinVar: RCV000010797
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Gitschier et al. (1985) identified this mutation due to a CGA-to-TGA change in codon 2326 in exon 26 in a patient with severe hemophilia A (306700). Nonsense mutations and a different missense (arg-to-gln) mutation have previously been observed in the same codon. It was pointed out that the G-to-T transversion is contrary to the rule of CG-to-TG mutations at CG dinucleotides, which represent the overwhelming majority. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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F8, ARG2209TER
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<br />
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SNP: rs137852355,
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ClinVar: RCV000010798, RCV003656621
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a severe case of hemophilia A (306700), Gitschier et al. (1985) found change in codon 2228 in exon 24 from CGA to TGA to result in conversion of arg2209 to stop. This mutation has also been found by others (Youssoufian et al., 1986). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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F8, EX26DEL
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<br />
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ClinVar: RCV000010799
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with severe hemophilia A (306700), Gitschier et al. (1985) found deletion of about 22 kb including exon 26. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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F8, ARG2116TER
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<br />
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SNP: rs137852356,
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gnomAD: rs137852356,
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ClinVar: RCV000010800, RCV002284167
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a case of severe hemophilia A (306700) (JH5), Youssoufian et al. (1986) found change of codon 2135 from CGA to TGA, resulting in conversion of amino acid 2116 to stop. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0005 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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|
<span class="mim-text-font">
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|
|
F8, EX6DEL
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<br />
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|
|
ClinVar: RCV000010801
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a case of severe hemophilia A (306700) (JH6), Youssoufian et al. (1987) found deletion of exon 6. </p><p>In a patient with severe hemophilia A (patient 2213), Levinson et al. (1990) found a deletion of exon 6 of the factor VIII gene. Schwaab et al. (1993) identified 2 patients with this deletion. See also Lin et al. (1993) and Antonarakis et al. (1995). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX14DEL
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|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010802
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|
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|
|
</span>
|
|
</div>
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|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a case of severe hemophilia A (306700) (JH7), Youssoufian et al. (1987) found deletion of exon 14. </p><p>In 3 patients with severe hemophilia A, Krepelova et al. (1992) found a deletion of exon 14 of the factor VIII gene. See also 300841.0029, 300841.0047, and 300841.0049. </p>
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|
</span>
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|
</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 HEMOPHILIA A</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
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|
|
F8, EX24-25DEL
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<br />
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|
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|
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|
|
ClinVar: RCV000010803
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a case of severe hemophilia A (306700) (JH8), Youssoufian et al. (1987) found deletion of exons 24 and 25. </p>
|
|
</span>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
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|
|
F8, EX23-25DEL
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<br />
|
|
|
|
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|
|
|
ClinVar: RCV000010804
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|
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</span>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a case of severe hemophilia A (306700) (JH9), Youssoufian et al. (1987) found deletion of exons 23-25. </p>
|
|
</span>
|
|
</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 HEMOPHILIA A</strong>
|
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</span>
|
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</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
|
|
|
|
F8, EX22DEL
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<br />
|
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|
|
|
|
|
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ClinVar: RCV000010805
|
|
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</span>
|
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</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a case of moderately severe hemophilia A (306700) (JH10), Youssoufian et al. (1987) found 'in-frame' deletion of exon 22. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 HEMOPHILIA A</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
|
|
F8, EX26DEL
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<br />
|
|
|
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|
|
ClinVar: RCV000010806
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a case of severe hemophilia A (306700) (JH12), Antonarakis et al. (1995) found deletion of exon 26. The mother showed mosaicism for this mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX1DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010807
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a case of severe hemophilia A (306700) (JH13), Youssoufian et al. (1988) found deletion of exon 1. </p><p>In a patient with severe hemophilia A (patient H309), Millar et al. (1990) found a deletion of exon 1 of the factor VIII gene. See also Wehnert et al. (1989), Higuchi et al. (1991), Schwaab et al. (1993), and Antonarakis et al. (1995), who reported patients with deletion of exon 1. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG2147TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852357,
|
|
|
|
|
|
|
|
ClinVar: RCV000010808
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a case of severe hemophilia A (306700) (JH14), Youssoufian et al. (1988) found a CGA to TGA change in codon 2166, resulting in a change in ARG2147 to a termination codon. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, NEW SPLICE DONOR, IVS4
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906429,
|
|
|
|
|
|
gnomAD: rs387906429,
|
|
|
|
|
|
ClinVar: RCV000010809, RCV003407314
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a case of mild hemophilia A (306700) (JH17), Youssoufian et al. (1988) found the creation of a new splice donor site created in intron 4 by a GAA to AAA change. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG2209GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852358,
|
|
|
|
|
|
|
|
ClinVar: RCV000010810, RCV000852189
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 cases of severe hemophilia A (306700) (JH18, JH19), Youssoufian et al. (1988) found a CGA-to-CAA change in codon 2228, resulting in substitution of glutamine for arginine as amino acid 2209. This mutation has also been found by others (Bernardi et al., 1989; Levinson et al., 1990; Traystman et al., 1990). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLU272GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852359,
|
|
|
|
|
|
|
|
ClinVar: RCV000010811
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Youssoufian et al. (1988) demonstrated the usefulness of DNA amplification followed by direct nucleotide sequencing in the search for mutations in X-linked disorders because of the unambiguous sequencing data obtained when the amplified DNA is from a male patient. In a 17-year-old Greek male with moderately severe hemophilia A (306700) (JH20), they detected a mutation by analysis of genomic DNA with TaqI; contrary to previous experience, the mutation was not a C-to-T or G-to-A transition. (The unifying mechanism of these mutations is thought to be methylation-induced C-to-T transitions at CpG dinucleotides involving either the coding or the complementary strand of DNA; see Bird (1980).) In this case the point mutation was in exon 7, where codon 291 for glutamate (GAA) was changed to one for glycine (GGA), leading to a change in amino acid 272 of the mature factor VIII protein. The mutation had arisen de novo in a germ cell of the patient's mother. The patient had 2% factor VIII activity, 3.5% factor VIII antigen, and moderate hemophilia A. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX2-3DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010812
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a case of severe hemophilia A (306700) (JH21), Youssoufian et al. (1988) found deletion of exons 2 and 3. </p><p>In a patient with severe hemophilia A (patient 656), Higuchi et al. (1988) found a deletion of exons 2-3 of the factor VIII gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX3-13DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010813
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a case of severe hemophilia A (306700) (JH22), Youssoufian et al. (1988) found deletion of exons 3-13. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX4-25DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010814
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a case of severe hemophilia A (306700) (JH23), Youssoufian et al. (1988) found deletion of exons 4-25. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX7-14DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010815
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a case of severe hemophilia A (306700) (JH24), Youssoufian et al. (1988) found deletion of exons 7-14. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 FACTOR VIII POLYMORPHISM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, LINE INS, IVS10
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010816
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a normal individual (JH25), Woods-Samuels et al. (1989) found insertion of 0.7 kb of LINE sequence in intron 10. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX26DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010817
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) (JH26), Youssoufian et al. (1988) found deletion of exon 26. Also see Gitschier et al. (1985) and Bernardi et al. (1989). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, LINE INS, EX14
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010818
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 brothers with severe hemophilia A (306700) (JH27, JH28), Kazazian et al. (1988) found insertion of 3.8 kb of LINE sequence in exon 14. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0023 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX15DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010819
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient (JH29) with severe hemophilia A (306700) and a translocation t(X;17), Antonarakis et al. (1995) found deletion of exon 15. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0024 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 2-BP DEL, EX8
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010916
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) (JH31), Higuchi et al. (1990) found deletion of GA from codon 360 GAA in exon 8. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0025 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG2307LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852360,
|
|
|
|
|
|
|
|
ClinVar: RCV000010821
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese patient with mild hemophilia A (306700) (JH32), Inaba et al. (1989) found a CGA-to-CTA change in codon 2326 in exon 26, resulting in substitution of leucine for arginine at amino acid 2307. PCR and nucleotide sequencing were used to identify the defect, which caused an alteration in a TaqI site. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0026 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG1941GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28937294,
|
|
|
|
|
|
|
|
ClinVar: RCV000010822, RCV000756109
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>{Antonarakis (unpublished observations)} reported a Japanese patient with mild hemophilia A (306700) with a CGA-to-CAA change t nucleotide 1960 in exon 18, resulting in substitution of glutamine for arginine at amino acid 1941. This mutation was also found in a Finnish patient by Levinson et al. (1990). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0027 FACTOR VIII (OKAYAMA)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG372HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28935499,
|
|
|
|
|
|
|
|
ClinVar: RCV000010823, RCV000757254, RCV000852002, RCV004812295
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a case of CRM-positive hemophilia A (306700) (JH35), Arai et al. (1989) found a change of arginine-372 to histidine, resulting from a CGC-to-CAC change in codon 391 in exon 8. The mutation was at the site of thrombin cleavage. Shima et al. (1989) found the same change in what they called factor VIII (Okayama). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0028 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLU1686TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852361,
|
|
|
|
|
|
gnomAD: rs137852361,
|
|
|
|
|
|
ClinVar: RCV000010824
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) (JH36), Higuchi et al. (1990) found a CAG-to-TAG change in codon 1705, causing replacement of glutamic acid 1686 by a stop signal. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0029 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX14DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010825
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) (JH37), Higuchi et al. (1989) found deletion of exon 14. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0030 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
FACTOR VIII (EAST HARTFORD)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG1689CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs111033613,
|
|
|
|
|
|
|
|
ClinVar: RCV000010826, RCV000010827, RCV001092277
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with moderately severe hemophilia A (306700) of a CRM-positive type, Gitschier (1988) found a CGC-to-TGC change in codon 1708 in exon 14, resulting in a change of arginine-1689 to cysteine. The mutation affects the thrombin cleavage site. The same mutation was subsequently found in additional patients (JH38, JH39) by Arai et al. (1990). Aly et al. (1992) found that cysteamine, which is known to modify mutant proteins with an arg-to-cys substitution, enhances the procoagulant activity of the mutant factor VIII, which they referred to as factor VIII-East Hartford. Aly and Hoyer (1992) demonstrated that the East Hartford mutant protein had procoagulant activity when separated from von Willebrand factor; this was taken to indicate that the dissociation of factor VIII from VWF is an essential effect of factor VIII light chain cleavage at arginine-1689. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0031 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, TYR1680PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28935203,
|
|
|
|
|
|
gnomAD: rs28935203,
|
|
|
|
|
|
ClinVar: RCV000010828, RCV002508187, RCV004975259
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with mild hemophilia A (306700) (JH40), Higuchi et al. (1990) found a TAT-to-TTT change in codon 1699, resulting in substitution of phenylalanine for tyrosine at amino acid 1680. The mutation affected the von Willebrand binding site. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0032 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, TYR1709CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852362,
|
|
|
|
|
|
|
|
ClinVar: RCV000010829
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with hemophilia A (306700) (JH41), Traystman et al. (1990) found a TAT-to-TGT change in codon 1728 of exon 14, leading to substitution of cysteine for tyrosine-1709. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0033 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX11-22DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010830
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a case of severe hemophilia A (306700) (JH1), Antonarakis et al. (1985) found deletion of exons 11-22. </p><p>(This allelic variant was originally entered into the database incorrectly as EX11-18DEL.)</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0034 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG1960TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852363,
|
|
|
|
|
|
gnomAD: rs137852363,
|
|
|
|
|
|
ClinVar: RCV000010831
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a case of severe hemophilia A (306700) (JH2), Antonarakis et al. (1985) found change in exon 18 from CGA to TGA which converted arg1960 to stop. Youssoufian et al. (1986) found the same mutation in another case of severe hemophilia A (JH3). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0035 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX3DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010832
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Higuchi et al. (1989) found a deletion of exon 3 about 2 kb in length. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0036 FACTOR VIII POLYMORPHISM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 7-KB DEL, IVS1
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010833
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Levinson et al. (1990) found a deletion of 7 kb from IVS1 as a presumed normal variant of factor VIII. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0037 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX1-5DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010834
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Higuchi et al. (1989) found a 35+ kb deletion removing exons 1 to 5. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0038 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX1-22DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010835
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Lillicrap et al. (1986) found a 127+ kb deletion that removed exons 1 to 22.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0039 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX26DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010836
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Higuchi et al. (1989) found deletion of exon 26. </p><p>In a patient with severe hemophilia A (patient HDX5), Bernardi et al. (1989) found a deletion of exon 26 of the factor VIII gene. This deletion was also reported by Nafa et al. (1990), Lavergne et al. (1992), Schwaab et al. (1993), and Antonarakis et al. (1995). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0040 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX1-26DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010837
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Casarino et al. (1986) found a 178+ kb deletion that removed exons 1 to 26.</p><p>In a patient with severe hemophilia A (patient H1) and factor VIII inhibitors, Casula et al. (1990) found a total deletion of the factor VIII gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0041 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG372CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852364,
|
|
|
|
|
|
|
|
ClinVar: RCV000010838
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This change was found in a case of moderately severe hemophilia A (306700) by Shima et al. (1989). The mutation is in the thrombin cleavage activator site. O'Brien et al. (1990) studied the relationship between structure and dysfunction. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0042 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG2307GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852360,
|
|
|
|
|
|
|
|
ClinVar: RCV000010839, RCV000851861, RCV001169905
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Gitschier et al. (1986) found this mutation in a case of mild hemophilia A (306700). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0043 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, LEU2166SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852365,
|
|
|
|
|
|
|
|
ClinVar: RCV000010840
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Levinson et al. (1990) found this mutation in a patient with less than 1% factor VIII activity and clinically severe hemophilia A (306700). The substitution was caused by a T-to-C transition at position 6555 in exon 23. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0044 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG2116PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852366,
|
|
|
|
|
|
gnomAD: rs137852366,
|
|
|
|
|
|
ClinVar: RCV000010841
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Levinson et al. (1987) found this mutation in a severe case of hemophilia A (306700). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0045 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, SER170LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852367,
|
|
|
|
|
|
|
|
ClinVar: RCV000010842, RCV003480026
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Chan et al. (1989) found this mutation in a moderately severe case of hemophilia A (306700). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0046 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX15-18DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010843
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Bardoni et al. (1988) found deletion of exons 15 to 18. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0047 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX14DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010844
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) with inhibitors, Higuchi et al. (1989) found deletion of exon 14. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0048 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX23-25DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010845
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Gitschier (1988) found deletion of exons 23 to 25 as a result of a complex rearrangement with deletion-duplication. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0049 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX14DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010846
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) accompanied by inhibitors, Mikami (1988) found deletion of exon 14. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0050 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX7-9DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010847
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) with inhibitors, Higuchi et al. (1989) found deletion of exons 7 to 9. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0051 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX5DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010848
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Levinson et al. (1990) found a 3- to 6-kb deletion removing exon 5. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0052 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX5DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010849
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Levinson et al. (1990) found a deletion of about 10 kb removing exon 5. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0053 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX5DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010850
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Briet et al. (1989) found a deletion of about 2 kb removing exon 5. Somatic and gonadal mosaicism was demonstrated in the mother.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0054 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX5-6 DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010851
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) with inhibitors, Levinson et al. (1990) found a deletion of 3-10 kb removing exons 5 and 6. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0055 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG336TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852368,
|
|
|
|
|
|
gnomAD: rs137852368,
|
|
|
|
|
|
ClinVar: RCV000010852
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Gitschier et al. (1986) found this mutation in a patient with severe hemophilia A (306700). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0056 REMOVED FROM DATABASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0057 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ASN1922ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852369,
|
|
|
|
|
|
|
|
ClinVar: RCV000010853
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Traystman et al. (1990) demonstrated this mutation in patients with hemophilia A (306700). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0058 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, CYS329ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906430,
|
|
|
|
|
|
|
|
ClinVar: RCV000010854
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Kogan and Gitschier (1990) demonstrated a thymine-to-cytosine mutation that changed the cysteine at codon 329 to an arginine. They used denaturing gel electrophoresis for this purpose. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0059 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, VAL326LEU
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|
|
<br />
|
|
|
|
SNP: rs137852371,
|
|
|
|
|
|
|
|
ClinVar: RCV000010855
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Kogan and Gitschier (1990) demonstrated a guanine-to-cytosine change within codon 326 resulting in a valine-to-leucine change. </p><p>Higuchi et al. (1990) found the same mutation in a patient with severe hemophilia A (JH30). </p>
|
|
</span>
|
|
</div>
|
|
|
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|
|
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<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0060 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
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|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 4-BP DEL, FS
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|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906431,
|
|
|
|
|
|
|
|
ClinVar: RCV000010856
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By means of denaturing gradient gel electrophoresis, Kogan and Gitschier (1990) demonstrated a deletion of 4 nucleotides within the region coding for the first acidic domain. The mutation caused a frameshift and a truncated protein product. The deletion occurred in a repetitive AAT and AAG motif. Small deletions in repeat sequences are thought to occur by a 'slipped mispairing' mechanism during DNA replication. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0061 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX13DUP
|
|
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|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010857
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with mild hemophilia A (306700), Murru et al. (1990) characterized a duplication in exon 13. The duplication was the result of nonhomologous breakage and reunion of 2 misaligned wildtype chromosomes. Sequence analysis of the breakpoint region showed AT-rich sequences and possible topoisomerase I sites, whose involvement in cases of illegitimate recombination has been postulated. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0062 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG427TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852372,
|
|
|
|
|
|
|
|
ClinVar: RCV000010858, RCV002247316
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Berg et al. (1990) took advantage of the fact that extremely low background levels of correctly spliced mRNA transcripts of tissue-specific genes can be demonstrated in a number of supposedly nonexpressing' cell types. This 'ectopic' or 'illegitimate' transcription was used to demonstrate the diagnostic utility of such transcripts in the construction of specific cDNAs derived from readily accessible 'nonexpressing' tissue, e.g., lymphocytes in the case of hemophilia A. Using PCR and direct sequencing, they demonstrated a novel mutation: a CGA-to-TGA transition at arginine 427. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0063 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLU1704LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852373,
|
|
|
|
|
|
|
|
ClinVar: RCV000010859
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with sporadic severe hemophilia A (306700), Paynton et al. (1991) identified a G-to-A transition resulting in substitution of lysine for glutamate-1704 (E1704K). The origin of the mutation was shown to be in the maternal grandfather who was 27 years old when his daughter was conceived. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0064 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, PRO2300SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852374,
|
|
|
|
|
|
gnomAD: rs137852374,
|
|
|
|
|
|
ClinVar: RCV000010860, RCV004700214
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a sporadic case of mild hemophilia A (306700), Paynton et al. (1991) demonstrated a C-to-T transition that resulted in mutation of serine for proline-2300. Paynton et al. (1991) used PCR amplification of specific alleles (PASA) to screen 96 unrelated hemophiliacs for the P2300S mutation; none of these patients had the mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0065 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, MET1772THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852375,
|
|
|
|
|
|
|
|
ClinVar: RCV000010861
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a study of the molecular defects responsible for crossreacting material-positive hemophilia A (306700), Aly et al. (1992) found 2 patients in whom the nonfunctional factor VIII-like protein had abnormal, slower-moving heavy or light chains on SDS/PAGE. Both patients had severe hemophilia A with less than 1% of normal factor VIII activity but with normal plasma level of factor VIII antigen. By denaturing gradient gel electrophoresis screening of PCR-amplified products of the factor VIII coding DNA sequence, followed by nucleotide sequencing of the abnormal PCR products, they identified in 1 patient a met1772-to-thr mutation that created a potential new N-glycosylation site at asparagine-1770 in the factor VIII light chain. In the second patient, an isoleucine-to-threonine substitution at position 566 created a potential new N-glycosylation site at asparagine-564 in the A2 domain of the factor VIII heavy chain. </p><p>Abnormal N-glycosylation, blocking factor VIII probe procoagulant activity, represented a previously unrecognized mechanism for the pathogenesis of severe hemophilia A.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0066 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ILE566THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852376,
|
|
|
|
|
|
|
|
ClinVar: RCV000010862
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 300841.0065.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0067 HEMOPHILIA A, SEVERE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, IVS22 INV
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010863
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Lakich et al. (1993) concluded that many mutations in the F8C gene result from recombination between homologous sequences within intron 22 of the F8C gene and those upstream of the gene. Such a recombination would lead to an inversion of all intervening DNA and a disruption of the gene. Among 23 patients with severe hemophilia A (306700), Naylor et al. (1993) found that approximately 40% were on the basis of this mutation involving intron 22. </p><p>It is hypothesized that the inversion mutations occur almost exclusively in germ cells during meiotic cell division by an intrachromosomal recombination between a 9.6-kb sequence within intron 22 and 1 of 2 almost identical copies located about 300 kb distal to the factor VIII gene at the telomeric end of the X chromosome. Most inversion mutations originate in male germ cells, where the lack of bivalent formation may facilitate flipping of the telomeric end of the single X chromosome. Oldenburg et al. (2000) reported the first instance of intron 22 inversion presenting as somatic mosaicism in a female, affecting only about 50% of lymphocyte and fibroblast cells of the proposita. Supposing a postzygotic de novo mutation as the usual cause of somatic mosaicism, the finding implies that the intron 22 inversion mutation is not restricted to meiotic cell divisions but can also occur during mitotic cell divisions, either in germ cell precursors or in somatic cells. </p><p>Lozier et al. (2002) found that the defect in the Chapel Hill hemophilia A dog colony started by Brinkhous and Graham (1950) replicates the F8 gene inversion commonly seen in humans with severe hemophilia A. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0068 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, IVS6DS, A-G, +3, 186-BP DEL, EX5-6 DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010896, RCV003934820
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Bidichandani et al. (1994) studied 15 randomly selected hemophilia A (306700) patients, 9 of whom were severely affected. They reported a new mutation affecting the intron 6 splice donor site in the factor VIII gene of 2 patients, that corresponds to an exon skipping event involving exon 5 and 6. The mutation is an A-to-G substitution at position +3 in the splice donor site of intron 6 in both the patients. This exon skipping event left the translational frame intact, and the resultant in-frame deletion of 186-bp in the mature mRNA is predicted to cause a shortening of the mature factor VIII polypeptide by 62 amino acid residues. Direct sequencing showed that exon 5 is consistently skipped along with exon 6 in the mature factor VIII mRNA. Both patients have a disease of moderate severity and residual factor VIII activity 3% of the normal. Bidichandani et al. (1994) noted that a patient lacking exon 5 and 6 in the mature factor VIII mRNA due to gross DNA deletion has previously been reported to have severe hemophilia A. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0069 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG-5TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906432,
|
|
|
|
|
|
|
|
ClinVar: RCV000010865, RCV003114181
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 patients with hemophilia A (306700), Pattinson et al. (1990) identified mutation of CGA to TGA at codon -5 in exon 1, resulting in a stop codon. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. This mutation has also been found by others (Reiner and Thompson, 1992). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0070 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, LEU7ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852377,
|
|
|
|
|
|
|
|
ClinVar: RCV000010866
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (306700). The mutation is caused by a CTG-to-CGG transversion at codon 7 in exon 1 of the A1 domain, resulting in arginine for leucine-7. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0071 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLU11VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852378,
|
|
|
|
|
|
|
|
ClinVar: RCV000010867
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Diamond et al. (1992) found this mutation in a patient with mild hemophilia A (306700). The substitution is caused by a GAA-to-GTA transversion at codon 11 in exon 1, resulting in valine for glutamic acid-11. This mutation is found in the A1 domain. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0072 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 89-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010868
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported in a patient with severe hemophilia A (306700) the deletion of 89 nucleotides from codon 14 to 29 in exon 1, resulting in a frameshift. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0073 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLY22CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852379,
|
|
|
|
|
|
gnomAD: rs137852379,
|
|
|
|
|
|
ClinVar: RCV000010869, RCV002247317
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this substitution in 2 patients with less than 1% factor VIII activity and severe hemophilia A (306700). The mutation is caused by a GGT-to-TGT transversion at codon 22 in exon 1 of the A1 domain, resulting in cysteine for glycine-22. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0074 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 10-BP INS, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2124149047,
|
|
|
|
|
|
|
|
ClinVar: RCV000010870
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Lin et al. (1993) identified the insertion of 10 nucleotides (TTCCATTCAA) resulting in a frameshift downstream from codon 38 in exon 2. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0075 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 2-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906433,
|
|
|
|
|
|
|
|
ClinVar: RCV000010871
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Lin et al. (1993) identified the deletion of 2 nucleotides (AA) resulting in a frameshift downstream from codon 48 in exon 2. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0076 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 4-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906434,
|
|
|
|
|
|
gnomAD: rs387906434,
|
|
|
|
|
|
ClinVar: RCV000010872, RCV004791212
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported in a patient with severe hemophilia A (306700) the deletion of 4 nucleotides (GTTT) resulting in a frameshift downstream from codon 50 in exon 2. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0077 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 2-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906435,
|
|
|
|
|
|
|
|
ClinVar: RCV000010873
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Antonarakis et al. (1995) reported the deletion of 2 nucleotides (GT) resulting in a frameshift downstream from codon 102 or 3 in exon 3. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0078 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 23-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000010874
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) identified in a patient with severe hemophilia A (306700) the deletion of 23 nucleotides resulting in a frameshift downstream from codon 104 in exon 3. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0079 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, IVS4AS, A-G, -2
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2124134457,
|
|
|
|
|
|
|
|
ClinVar: RCV000010875
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported the substitution of A to G at the second nucleotide of the acceptor splice site of intron 4, resulting in abnormal splicing. The patient had 1.7% factor VIII activity, 1.3% factor VIII antigen, and a severe hemophilia A (306700). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0080 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLY70ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852380,
|
|
|
|
|
|
|
|
ClinVar: RCV000010876
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this gly70-to-asp mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (306700). The mutation is caused by a GGT-to-GAT transition at codon 70 in exon 3 of the A1 domain. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0081 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLY73VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852381,
|
|
|
|
|
|
|
|
ClinVar: RCV000010877
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Diamond et al. (1992) found this mutation in a patient with mild hemophilia A (306700). The mutation is caused by a GGT-to-GTT transversion at codon 73 in exon 3 of the A1 domain, resulting in valine for glycine-73. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0082 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, VAL80ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852382,
|
|
|
|
|
|
|
|
ClinVar: RCV000010878
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this val80-to-asp mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (306700). The mutation is caused by a GTT-to-GAT transversion at codon 80 in exon 3 of the A1 domain. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0083 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, VAL85ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852383,
|
|
|
|
|
|
|
|
ClinVar: RCV000010879
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Diamond et al. (1992) found this val85-to-asp mutation in a patient with mild hemophilia A (306700). The mutation is caused by a GTC-to-GAC transversion at codon 85 in exon 3 of the A1 domain. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0084 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, LYS89THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852384,
|
|
|
|
|
|
|
|
ClinVar: RCV000010880, RCV000508582, RCV002247318
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this lys89-to-thr mutation in a patient with mild hemophilia A (306700). The mutation is caused by an AAG-to-ACG transversion at codon 89 in exon 3 of the A1 domain. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0085 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, MET91VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852385,
|
|
|
|
|
|
|
|
ClinVar: RCV000010881
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in a patient with moderate hemophilia A (306700). The mutation is caused by an ATG-to-GTG transition at codon 91 in exon 3 of the A1 domain, resulting in valine for methionine-91. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0086 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, LEU98ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852386,
|
|
|
|
|
|
|
|
ClinVar: RCV000010882
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (306700). It is caused by a CTT-to-CGT transversion at codon 98 in exon 3 of the A1 domain, resulting in arginine for leucine-98. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0087 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLY130ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852387,
|
|
|
|
|
|
|
|
ClinVar: RCV000010883
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with less than 1% factor VIII activity and severe hemophilia A (306700), Lin et al. (1993) identified a GGA-to-CGA transversion at codon 111 in exon 3 of the A1 domain of the F8 gene, resulting in arginine for glycine-111. Including the 19-amino acid signal peptide of the F8 gene (Vehar et al., 1984), the mutation is designated gly130-to-arg (G130R). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0088 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLU132ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852388,
|
|
|
|
|
|
gnomAD: rs137852388,
|
|
|
|
|
|
ClinVar: RCV000010884, RCV001529373, RCV002247319, RCV002280860, RCV002496321, RCV003952352
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported a glu113-to-asp mutation in a patient with less than 1% factor VIII activity, severe hemophilia A (306700) and inhibitors. It is caused by a GAA-to-GAC transversion at codon 113 in exon 4 of the A1 domain of factor VIII. Including the 19-amino acid signal peptide of the F8 gene (Vehar et al., 1984), this mutation is designated glu132-to-asp (E132D). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0089 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, TYR114CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852389,
|
|
|
|
|
|
|
|
ClinVar: RCV000010885
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this tyr114-to-cys mutation in a patient with 6.3% factor VIII activity, 10.7% factor VIII antigen, and mild hemophilia A (306700). The mutation is caused by a TAT-to-TGT transition at codon 114 in exon 4. This mutation is found in the A1 domain of factor VIII. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0090 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ASP116GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852390,
|
|
|
|
|
|
|
|
ClinVar: RCV000010886
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (306700). The mutation is caused by a GAT-to-GGT transition at codon 116 in exon 4 of the A1 domain, resulting in glycine for aspartic acid-116. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0091 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, THR137ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852391,
|
|
|
|
|
|
|
|
ClinVar: RCV000010887, RCV004799739
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with 2% factor VIII activity, 10.7% factor VIII antigen, and moderate hemophilia A (306700). The mutation is caused by an ACC-to-ATC transition at codon 118 in exon 4 of the A1 domain, resulting in isoleucine for threonine-118. Including the 19-amino acid signal peptide of the F8 gene (Vehar et al., 1984), this mutation is designated thr137-to-ile (T137I). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0092 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLY145VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852392,
|
|
|
|
|
|
gnomAD: rs137852392,
|
|
|
|
|
|
ClinVar: RCV000010888
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Diamond et al. (1992) found this gly145-to-val mutation in a patient with mild hemophilia A (306700). The mutation is caused by a GGT-to-GTT transversion at codon 145 in exon 4 of the A1 domain. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0093 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, PRO146SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852393,
|
|
|
|
|
|
gnomAD: rs137852393,
|
|
|
|
|
|
ClinVar: RCV000010889, RCV003657257
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Lin et al. (1993) found a pro146-to-ser mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (306700). The mutation is caused by a CCA-to-TCA transition at codon 146 in exon 4 of the A1 domain. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0094 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, VAL162MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852394,
|
|
|
|
|
|
|
|
ClinVar: RCV000010890, RCV000851946, RCV001701720, RCV003398478
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Diamond et al. (1992) found this mutation in 5 patients with 3.5-8.5% factor VIII activity, 6-35.9% factor VIII antigen, and moderate to mild hemophilia A (306700). A GTG-to-ATG transition at codon 162 in exon 4 of the A1 domain resulted in a val162-to-met change. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0095 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, LYS166THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852395,
|
|
|
|
|
|
|
|
ClinVar: RCV000010891
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this lys166-to-thr mutation in a patient with 19% factor VIII activity and mild hemophilia A (306700). The mutation is caused by an AAA-to-ACA transversion at codon 166 in exon 4 of the A1 domain. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0096 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ASP203VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852396,
|
|
|
|
|
|
|
|
ClinVar: RCV000010892
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with 2% factor VIII activity, 8.5% factor VIII antigen, and moderate hemophilia A (306700). The mutation is caused by a GAT-to-GTT transversion at codon 203 in exon 5 of the A1 domain and resulted in valine for aspartic acid-203. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0097 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLY205TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852397,
|
|
|
|
|
|
|
|
ClinVar: RCV000010893
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in a patient with 3.2% factor VIII activity and moderate hemophilia A (306700). The mutation is caused by a GGG-to-TGG transversion at codon 205 in exon 5 of the A1 domain, resulting in tryptophan for glycine-205. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0098 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 2-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906436,
|
|
|
|
|
|
|
|
ClinVar: RCV000010894
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Lin et al. (1993) identified the deletion of 2 nucleotides (AG) resulting in a frameshift downstream from codon 210-211 in exon 6. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0099 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, IVS5AS, A-G, -2
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2124131475,
|
|
|
|
|
|
|
|
ClinVar: RCV000010895
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with less than 1% factor VIII activity and severe hemophilia A (306700), Naylor et al. (1991) identified an A-to-G transition at the second nucleotide of the acceptor splice site of intron 5, which resulted in abnormal splicing. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0100 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, IVS6DS, A-G, +3
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2073548872,
|
|
|
|
|
|
|
|
ClinVar: RCV000010896, RCV003934820
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with 3-4% factor VIII activity and moderate hemophilia A (306700), Bidichandani et al. (1994) identified mutation of A to G at the third nucleotide of the donor splice site of intron 6, which resulted in abnormal splicing. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0101 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, IVS6AS, G-C, -1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2073445259,
|
|
|
|
|
|
|
|
ClinVar: RCV001265089
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported a patient with less than 1% factor VIII activity and severe hemophilia A (306700) who had a G-to-C transversion. The mutation was in the first nucleotide of the acceptor splice site of intron 6 and resulted in abnormal splicing ({Antonarakis and Kazazian, unpublished}). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0102 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLY266GLU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852398,
|
|
|
|
|
|
|
|
ClinVar: RCV000010898
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Eckhardt et al. (2013) noted that a gly266-to-glu (G266E) mutation in the F8 gene (gly247-to-glu in the mature protein) had been found in patients with hemophilia A (306700). </p><p>Antonarakis et al. (1995) had reported this mutation as a gly247-to-gln substitution caused by a GGA-to-GAA transition at codon 247 in exon 7 of the A1 domain. The patient had less than 1% factor VIII activity and severe hemophilia A. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0103 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, TRP274TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs34371500,
|
|
|
|
|
|
|
|
ClinVar: RCV000010899
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with hemophilia A (306700), Antonarakis et al. (1995) reported mutation of TGG-to-TGA at codon 255 in exon 7, resulting in a stop codon. Including the 19-amino acid signal peptide of the F8 gene (Vehar et al., 1984), this mutation is designated trp274-to-ter (W274X). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0104 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLY278ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852399,
|
|
|
|
|
|
|
|
ClinVar: RCV000010900
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (306700). The mutation is caused by a GGA-to-AGA transition at codon 259 in exon 7 of the A1 domain, resulting in arginine for glycine-259. Including the 19-amino acid signal peptide of the F8 gene (Vehar et al., 1984), this mutation is designated gly6278-to-arg (G278R). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0105 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 1-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906437,
|
|
|
|
|
|
|
|
ClinVar: RCV000010901
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Antonarakis et al. (1995) reported the deletion of 1 nucleotide (T) resulting in a frameshift downstream from codon 264 in exon 7. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0106 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, VAL266GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852400,
|
|
|
|
|
|
|
|
ClinVar: RCV000010902
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in a patient with mild hemophilia A (306700). The mutation is caused by a GTG-to-GGG transversion at codon 266 in exon 7 of the A1 domain, resulting in glycine for valine-266. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0107 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, THR275ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852401,
|
|
|
|
|
|
|
|
ClinVar: RCV000010903
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with 4-4.8% factor VIII activity, 20-40% factor VIII antigen, and moderate hemophilia A (306700). The mutation is caused by a ACA-to-ATA transition at codon 275 in exon 7 of the A1 domain, resulting in isoleucine for threonine-275. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0108 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ASN280ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852402,
|
|
|
|
|
|
|
|
ClinVar: RCV000010904
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Pieneman et al. (1993) found this mutation in a patient with 8-12% factor VIII activity and mild hemophilia A (306700). The mutation is caused by a AAC-to-ATC transversion at codon 280 in exon 7 of the A1 domain, resulting in isoleucine for asparagine-280. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0109 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG282HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852403,
|
|
|
|
|
|
|
|
ClinVar: RCV000010905, RCV000255290, RCV004745151
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in a patient with less than 1% factor VIII activity, 18% factor VIII antigen, and severe hemophilia A (306700). A CGC-to-CAC transition at codon 282 in exon 7 of the A1 domain results in an arg282-to-his change. The G-to-A transition follows the rule of CG-to-CA mutations at CG dinucleotides. This mutation has also been found by others (McGinniss et al., 1993; Naylor et al., 1993). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0110 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG282LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852403,
|
|
|
|
|
|
|
|
ClinVar: RCV000010906
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in 2 patients with less than 1% factor VIII activity and severe hemophilia A (306700). It is caused by a CGC-to-CTC transversion at codon 282 in exon 7 of the A1 domain, resulting in leucine for arginine-282. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0111 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 1-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906438,
|
|
|
|
|
|
|
|
ClinVar: RCV000010907
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Antonarakis et al. (1995) reported the deletion of 1 nucleotide (G), resulting in a frameshift downstream from codon 283 in exon 7. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0112 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, SER289LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852404,
|
|
|
|
|
|
|
|
ClinVar: RCV000010908, RCV003415685
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>McGinniss et al. (1993) found this substitution in a patient with 37% factor VIII activity, 106% factor VIII antigen and mild hemophilia A (306700). The mutation is caused by a TCG-to-TTG transition at codon 289 in exon 7 of the A1 domain, resulting in leucine for serine-289. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0113 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, PHE293SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852405,
|
|
|
|
|
|
|
|
ClinVar: RCV000010909, RCV000852250, RCV003656098
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in 3 patients with 7-21.5% factor VIII activity, 2-17.9% factor VIII antigen, and mild hemophilia A (306700). An ACT-to-GCT transition at codon 295 in exon 7 of the A1 domain results in alanine for threonine-295. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0114 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, THR314ALA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852406,
|
|
|
|
|
|
gnomAD: rs137852406,
|
|
|
|
|
|
ClinVar: RCV000010910, RCV004566717
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in 3 patients with 7-21.5% factor VIII activity, 2-17.9% factor VIII antigen, and mild hemophilia A (306700). The mutation is caused by an ACT-to-GCT transition at codon 295 in exon 7 of the A1 domain, resulting in alanine for threonine-295. Including the 19-amino acid signal peptide of the F8 gene (Vehar et al., 1984), this mutation is designated thr314-to-ala (T314A). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0115 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 1-BP DEL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906439,
|
|
|
|
|
|
|
|
ClinVar: RCV000010911
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>(Antonarakis et al. (1995)) reported in a patient with severe hemophilia A (306700) the deletion of 1 nucleotide (G), resulting in a frameshift downstream from codon 296 in exon 7. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0116 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, LEU308PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852407,
|
|
|
|
|
|
|
|
ClinVar: RCV000010912
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (306700). The mutation is caused by a CTG-to-CCG transition at codon 308 in exon 7 of the A1 domain, resulting in proline for leucine-308. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0117 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, TYR342TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852408,
|
|
|
|
|
|
|
|
ClinVar: RCV000010913
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 1 patient with hemophilia A (306700), Lin et al. (1993) identified a TAT-to-TAA substitution at codon 323 in exon 8, resulting in a stop codon. Including the 19-amino acid signal peptide of the F8 gene (Vehar et al., 1984), this mutation is designated tyr342-to-ter (W342X). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0118 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, CYS329TYR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852409,
|
|
|
|
|
|
|
|
ClinVar: RCV000010914
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (306700). The mutation is caused by a TGT-to-TAT transition at codon 329 in exon 8 of the A1 domain, resulting in tyrosine for cysteine-329. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0119 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, CYS348SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852410,
|
|
|
|
|
|
|
|
ClinVar: RCV000010915
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with 2.6% factor VIII activity, 3.2% factor VIII antigen, and moderate hemophilia A (306700). The mutation is caused by a TGT-to-TCT transversion at codon 329 in exon 8 of the A1 domain, resulting in serine for cysteine-329. Including the 19-amino acid signal peptide of the F8 gene (Vehar et al., 1984), this mutation is designated cys348-to-ser (C348S). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0120 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 2-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906440,
|
|
|
|
|
|
|
|
ClinVar: RCV000010916
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Higuchi et al. (1990) identified the deletion of 2 nucleotides (GA) resulting in a frameshift downstream from codon 341 in exon 8. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0121 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, SER392TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933668,
|
|
|
|
|
|
|
|
ClinVar: RCV000010917
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 1 patient with hemophilia A (306700), Acquila et al. (1993) identified a TCA-to-TAA substitution at codon 373 in exon 8, resulting in a stop codon. Including the 19-amino acid signal peptide of the F8 gene (Vehar et al., 1984), this mutation is designated ser392-to-ter (S392X). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0122 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, SER373LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933668,
|
|
|
|
|
|
|
|
ClinVar: RCV000010918, RCV003114182
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Acquila et al. (1993) found this mutation in a patient with 8% factor VIII activity and mild hemophilia A (306700). The mutation is caused by a TCA-to-TTA transition at codon 373 in exon 8, resulting in leucine for serine-373. The mutation has been shown to abolish normal cleavage by thrombin. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0123 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, SER373PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933669,
|
|
|
|
|
|
|
|
ClinVar: RCV000010919
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Johnson et al. (1994) found this mutation in a patient with 10% factor VIII activity, 100% factor VIII antigen, and mild hemophilia A (306700). The mutation is caused by a TCA-to-CCA transition at codon 373 in exon 8, resulting in proline for serine-373. The mutation abolishes normal cleavage by thrombin. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0124 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 2-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906441,
|
|
|
|
|
|
|
|
ClinVar: RCV000010920
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Antonarakis et al. (1995) reported the deletion of 2 nucleotides (AA), resulting in a frameshift downstream from codon 381-382 in exon 8. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0125 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ILE386SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933670,
|
|
|
|
|
|
|
|
ClinVar: RCV000010921
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Lin et al. (1993) found this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (306700). The mutation is caused by an ATT-to-AGT transversion at codon 386 in exon 8 of the A2 domain, resulting in serine for isoleucine-386. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0126 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLU390GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933671,
|
|
|
|
|
|
|
|
ClinVar: RCV000010922
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in 2 patients with less than 1-3.3% factor VIII activity and severe to moderate hemophilia A (306700). The mutation is caused by a GAG-to-GGG transition at codon 390 in exon 8 of the A2 domain, resulting in glycine for glutamic acid-390. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0127 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, LEU412PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933672,
|
|
|
|
|
|
|
|
ClinVar: RCV000010923
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in 2 patients with 5-10.5% factor VIII activity and moderate to mild hemophilia A (306700). The mutation is caused by a TTG-to-TTT transversion at codon 412 in exon 9 of the A2 domain, resulting in phenylalanine for leucine-412. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0128 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 1-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906442,
|
|
|
|
|
|
|
|
ClinVar: RCV000010924
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Lin et al. (1993) identified the deletion of 1 nucleotide (G), resulting in a frameshift downstream from leucine-412 in exon 9. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0129 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, LYS425ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28937272,
|
|
|
|
|
|
|
|
ClinVar: RCV000010925
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in a patient with less than 1% factor VIII activity, 5% factor VIII antigen, and severe hemophilia A (306700). The mutation is caused by a AAA-to-AGA transition at codon 425 in exon 9 of the A2 domain, resulting in arginine for lysine-425. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0130 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, TYR431ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs111033616,
|
|
|
|
|
|
|
|
ClinVar: RCV000010926
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Pieneman et al. (1993) found this mutation in a patient with 4% factor VIII activity and moderate hemophilia A (306700). The mutation is caused by a TAC-to-AAC transversion at codon 431 in exon 9 of the A2 domain, resulting in asparagine for tyrosine-431. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0131 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, TYR473HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906443,
|
|
|
|
|
|
|
|
ClinVar: RCV000010927
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in a patient with mild hemophilia A (306700). The mutation is caused by a TAT-to-CAT transition at codon 473 in exon 10 of the A2 domain, resulting in histidine for tyrosine-473. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0132 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, TYR473CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906444,
|
|
|
|
|
|
|
|
ClinVar: RCV000010928
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in 2 patients with 2.7-3.5% factor VIII activity and moderate hemophilia A (306700). The mutation is caused by a TAT-to-TGT transition at codon 473 in exon 10 of the A2 domain, resulting in cysteine for tyrosine-473. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0133 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ILE475THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852413,
|
|
|
|
|
|
|
|
ClinVar: RCV000010929
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with 5-5.7% factor VIII activity, 6.9-8.8% factor VIII antigen, and mild hemophilia A (306700). The mutation is caused by an ATC-to-ACC transition at codon 475 in exon 10 of the A2 domain, resulting in threonine for isoleucine-475. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0134 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLY498ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852414,
|
|
|
|
|
|
|
|
ClinVar: RCV000010930, RCV000851700
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Naylor et al. (1993) found this mutation in a patient with 2% factor VIII activity and moderate hemophilia A (306700). The mutation was caused by a GGA-to-AGA transition in the F8 gene, resulting in a gly479-to-arg substitution. Antonarakis et al. (1995) stated that this mutation occurred in exon 10 of the A2 domain and had been reported in 2 other patients with hemophilia A. Including the 19-amino acid signal peptide of the F8 gene (Vehar et al., 1984), this mutation is designated gly498-to-arg (G498R). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0135 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 11-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2124099163,
|
|
|
|
|
|
|
|
ClinVar: RCV000010931
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Lin et al. (1993) identified the deletion of 11 nucleotides (CCGTCCTTTGT) between codon 483 and 487 in exon 10. The deletion results in a frameshift. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0136 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, IVS10AS, G-T, +1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1414679955,
|
|
|
|
|
|
|
|
ClinVar: RCV000010932
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with mild hemophilia A (306700), Economou et al. (1992) identified a G-to-T transversion in codon 504. This mutation, which did not result in amino acid substitution, occurs in the first nucleotide of exon 11 and alters the sequence of the acceptor splice site of intron 10. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0137 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 1-BP INS, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906445,
|
|
|
|
|
|
|
|
ClinVar: RCV000010933
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Economou et al. (1992) identified the insertion of 1 nucleotide (G), resulting in a frameshift downstream from codon 513 or 514 in exon 11. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0138 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ASP525ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852415,
|
|
|
|
|
|
|
|
ClinVar: RCV000010934
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with 6% factor VIII activity, 61% factor VIII antigen, and moderate hemophilia A (306700). The mutation is caused by a GAT-to-AAT transition at codon 525 in exon 11 of the A2 domain, resulting in asparagine for aspartic acid-525. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0139 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG527TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852416,
|
|
|
|
|
|
|
|
ClinVar: RCV000010935, RCV000852048, RCV003103711
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in a patient with 9.5-38% factor VIII activity, 43-245% factor VIII antigen, and mild hemophilia A (306700). The mutation is caused by a CGG-to-TGG transition at codon 527 in exon 11 of the A2 domain, resulting in tryptophan for arginine-527. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. This mutation has also been found by others (McGinniss et al., 1993; see also Antonarakis et al., 1995). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0140 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG531CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852417,
|
|
|
|
|
|
|
|
ClinVar: RCV000010936, RCV004595878
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in 3 patients with 4.2-6.7% factor VIII activity and moderate to mild hemophilia A (306700). The mutation is caused by a CGC-to-TGC transition at codon 531 in exon 11 of the A2 domain, resulting in cysteine for arginine-531. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. This mutation has also been found by others (Economou et al., 1992 and Diamond et al., 1992). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0141 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG531GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852417,
|
|
|
|
|
|
|
|
ClinVar: RCV000010937, RCV000757245
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in a patient with 9.2% factor VIII activity and mild hemophilia A (306700). The mutation is caused by a CGC-to-GGC transversion at codon 531 in exon 11 of the A2 domain, resulting in glycine for arginine-531. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0142 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG531HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852418,
|
|
|
|
|
|
gnomAD: rs137852418,
|
|
|
|
|
|
ClinVar: RCV000010938, RCV003656622, RCV005042025
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with 23.5-32% factor VIII activity, 20-33.2% factor VIII antigen and mild hemophilia A (306700). The mutation is caused by a CGC-to-CAC transition at codon 531 in exon 11 of the A2 domain, resulting in histidine for arginine-531. The G-to-A transition follows the rule of CG-to-CA mutations at CG dinucleotides. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0143 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, SER535GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852419,
|
|
|
|
|
|
gnomAD: rs137852419,
|
|
|
|
|
|
ClinVar: RCV000010939, RCV000727106, RCV003934821
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in 2 patients with mild hemophilia A (306700). The mutation is caused by a AGT-to-GGT transition at codon 535 in exon 11 of the A2 domain, resulting in glycine for serine-535. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0144 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ASP542GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852420,
|
|
|
|
|
|
|
|
ClinVar: RCV000010940
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in a patient with less than 1% factor VIII activity, 5% factor VIII antigen, and severe hemophilia A (306700). The mutation is caused by a GAT-to-GGT transition at codon 542 in exon 11 of the A2 domain, resulting in glycine for aspartic acid-542. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0145 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLU557TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852421,
|
|
|
|
|
|
|
|
ClinVar: RCV000010941
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with hemophilia A (306700), Diamond et al. (1992) identified a GAA-to-TAA substitution at codon 557 in exon 11, resulting in a stop codon. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0146 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, SER558PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28937282,
|
|
|
|
|
|
|
|
ClinVar: RCV000010942
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>McGinniss et al. (1993) found this mutation in a patient with 21% factor VIII activity, 175% factor VIII antigen, and mild hemophilia A (306700). The mutation is caused by a TCT-to-TTT transition at codon 558 in exon 11 of the A2 domain, resulting in phenylalanine for serine-558. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0147 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLN565LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852422,
|
|
|
|
|
|
|
|
ClinVar: RCV000010943
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in 2 patients with 6.8% factor VIII activity and moderate to mild hemophilia A (306700). The mutation is caused by a CAG-to-AAG transversion at codon 565 in exon 11 of the A2 domain, resulting in lysine for glutamine-565. This mutation has also been found by others (Antonarakis et al., 1995). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0148 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, SER577PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906446,
|
|
|
|
|
|
|
|
ClinVar: RCV000010944
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Reiner and Thompson (1992) found this mutation in 5 patients with less than 1% factor VIII activity and severe hemophilia A (306700). The mutation is caused by a TCT-to-CCT transition at codon 577 in exon 12 of the A2 domain, resulting in proline for serine-577. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. This mutation has also been found by others (Antonarakis et al., 1995). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0149 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG583TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852424,
|
|
|
|
|
|
gnomAD: rs137852424,
|
|
|
|
|
|
ClinVar: RCV000010945, RCV000852054
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 patients with hemophilia A (306700), Pattinson et al. (1990) identified a CGA-to-TGA substitution at codon 583 in exon 12, resulting in a stop codon. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. This mutation has also been found by others (Reiner and Thompson, 1992; see also Antonarakis et al., 1995). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0150 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, SER584ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852425,
|
|
|
|
|
|
|
|
ClinVar: RCV000010946
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with hemophilia A (306700). The mutation is caused by a AGC-to-ATC transversion at codon 584 in exon 12 of the A2 domain, resulting in isoleucine for serine-584. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0151 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, TRP604CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852426,
|
|
|
|
|
|
|
|
ClinVar: RCV000010947
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Lin et al. (1993) found this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (306700). The mutation is caused by a TGG-to-TGC transversion at codon 585 in exon 12 of the A2 domain, resulting in cysteine for tryptophan-585. Including the 19-amino acid signal peptide of the F8 gene (Vehar et al., 1984), this mutation is designated trp604-to-cys (W604C). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0152 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, TYR586SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852427,
|
|
|
|
|
|
|
|
ClinVar: RCV000010948
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Lin et al. (1993) found this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (306700). The mutation is caused by a TAC-to-TCC transversion at codon 586 in exon 12 of the A2 domain, resulting in serine for tyrosine-586. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0153 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG593CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852428,
|
|
|
|
|
|
gnomAD: rs137852428,
|
|
|
|
|
|
ClinVar: RCV000010949, RCV000413577, RCV000851933, RCV002247320, RCV004540992
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in a patient with mild to moderate hemophilia A (306700). The mutation is caused by a CGC-to-TGC transition at codon 593 in exon 12 of the A2 domain, resulting in cysteine for arginine-593. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. This mutation has also been found by others (Naylor et al., 1993 and Diamond et al., 1992; see also Antonarakis et al., 1995). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0154 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ASN612SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852429,
|
|
|
|
|
|
|
|
ClinVar: RCV000010950
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with hemophilia A (306700). The mutation is caused by a AAC-to-AGC transition at codon 612 in exon 12 of the A2 domain, resulting in serine for asparagine-612. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0155 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, IVS12DS, G-A, +5
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2124090120,
|
|
|
|
|
|
|
|
ClinVar: RCV000010951
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with mild hemophilia A (306700), Antonarakis et al. (1995) reported a G-to-A transition. The mutation is at the fifth nucleotide of the donor splice site of intron 12 and results in abnormal splicing. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0156 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, VAL634ALA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852430,
|
|
|
|
|
|
|
|
ClinVar: RCV000010952
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>McGinniss et al. (1993) found this mutation in a patient with 5% factor VIII activity, 138% factor VIII antigen, and mild hemophilia A (306700). The mutation is caused by a GTG-to-GCG transition at codon 634 in exon 13 of the A2 domain, resulting in alanine for valine-634. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0157 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, VAL634MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852431,
|
|
|
|
|
|
|
|
ClinVar: RCV000010953
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>McGinniss et al. (1993) found a val634-to-met mutation in 2 patients with less than 1% factor VIII activity, 175% factor VIII antigen, and severe hemophilia A (306700). The mutation is caused by a GTG-to-ATG transition at codon 634 in exon 13 of the A2 domain. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0158 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, TYR655TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852432,
|
|
|
|
|
|
|
|
ClinVar: RCV000010954
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 patients with hemophilia A (306700) (1 with inhibitors), Antonarakis et al. (1995) reported the substitution of TAC-to-TAG at codon 636 in exon 13, resulting in a stop codon. Including the 19-amino acid signal peptide of the F8 gene (Vehar et al., 1984), this mutation is designated trp655-to-cys (W604C). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0159 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ALA644VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852433,
|
|
|
|
|
|
|
|
ClinVar: RCV000010955
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in a patient with 14% factor VIII activity, 25% factor VIII antigen, and mild hemophilia A (306700). The mutation is caused by a GCA-to-GTA transition at codon 644 in exon 13 of the A2 domain, resulting in valine for alanine-644. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0160 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 3-BP DEL, PHE652DEL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1476178386,
|
|
|
|
|
|
|
|
ClinVar: RCV000010956
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with 1.4% factor VIII activity, 12% factor VIII antigen, and severe hemophilia A (306700), McGinniss et al. (1993) identified an in-frame deletion of 3 bp corresponding to codon 652 (TTC) in exon 13 of the A2 domain, resulting in the deletion of phenylalanine-652. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0161 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, PHE677LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852434,
|
|
|
|
|
|
|
|
ClinVar: RCV000010957
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with 5.1% factor VIII activity, 50.5% factor VIII antigen, and moderate hemophilia A (306700). The mutation is caused by a TTC-to-CTC transition at codon 658 in exon 13 of the A2 domain, resulting in leucine for phenylalanine-658. Including the 19-amino acid signal peptide of the F8 gene (Vehar et al., 1984), this mutation is designated phe677-to-leu (F677L). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0162 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG698TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852435,
|
|
|
|
|
|
gnomAD: rs137852435,
|
|
|
|
|
|
ClinVar: RCV000010958, RCV000851590, RCV000851937, RCV002247321, RCV002281701, RCV002490350
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Diamond et al. (1992) found this mutation in a patient with mild hemophilia A (306700). The mutation is caused by a CGG-to-TGG transition at codon 698 in exon 14 of the A2 domain, resulting in tryptophan for arginine-698. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0163 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ALA704THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852436,
|
|
|
|
|
|
gnomAD: rs137852436,
|
|
|
|
|
|
ClinVar: RCV000010959, RCV000852072, RCV001560529, RCV002490351
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in 3 patients with a mild to moderate hemophilia A (306700). The mutation is caused by a GCC-to-ACC transition at codon 704 in exon 14 of the A2 domain, resulting in threonine for alanine-704. The G-to-A transition follows the rule of CG-to-CA mutations at CG dinucleotides. See also Antonarakis et al. (1995). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0164 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLU720LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28937285,
|
|
|
|
|
|
gnomAD: rs28937285,
|
|
|
|
|
|
ClinVar: RCV000010960, RCV004745152
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this glu720-to-lys mutation in 2 patients with 12.5-30% factor VIII activity, less than 20% factor VIII antigen, and a mild hemophilia A (306700). The mutation is caused by a GAG-to-AAG transition at codon 720 in exon 14 of the A2 domain. The G-to-A transition follows the rule of CG-to-CA mutations at CG dinucleotides. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0165 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG795TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2228152,
|
|
|
|
|
|
gnomAD: rs2228152,
|
|
|
|
|
|
ClinVar: RCV000010961
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with hemophilia A (306700), Pattinson et al. (1990) identified the substitution of CGA-to-TGA at codon 795 in exon 14, resulting in a stop codon. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0166 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 1-BP INS, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906447,
|
|
|
|
|
|
|
|
ClinVar: RCV000010962
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Naylor et al. (1993) identified the insertion of 1 nucleotide (A) at codon 961-2 or 3 in exon 14. The mutation results in a frameshift. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0167 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 2-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906448,
|
|
|
|
|
|
|
|
ClinVar: RCV000010963
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Lin et al. (1993) identified the deletion of 2 nucleotides (AG) that results in a frameshift downstream from codon 969 in exon 14. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0168 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLU1038LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933673,
|
|
|
|
|
|
gnomAD: rs28933673,
|
|
|
|
|
|
ClinVar: RCV000010964, RCV000601703, RCV002247322, RCV004791213
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) and McGinniss et al. (1993) found this mutation in a patient with 2.4% factor VIII activity, 15% factor VIII antigen, and moderate hemophilia A (306700). The mutation is caused by a GAG-to-AAG transition at codon 1038 in exon 14 of the B domain, resulting in lysine for glutamic acid-1038. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0169 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 2-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906449,
|
|
|
|
|
|
|
|
ClinVar: RCV000010965
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Lin et al. (1993) identified the deletion of 2 nucleotides (AA) resulting in a frameshift downstream from codon 1164 in exon 14. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0170 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 1-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906450,
|
|
|
|
|
|
gnomAD: rs387906450,
|
|
|
|
|
|
ClinVar: RCV000010966, RCV000851976, RCV004721244
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 patients with severe hemophilia A (306700), Lin et al. (1993) identified the deletion of 1 nucleotide (A) resulting in a frameshift downstream from codon 1194 in exon 14. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0171 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 1-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906451,
|
|
|
|
|
|
|
|
ClinVar: RCV000010967
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Naylor et al. (1993) identified the deletion of 1 nucleotide (C) resulting in a frameshift downstream from codon 1212 in exon 14. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0172 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 2-BP, INS, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2124049493,
|
|
|
|
|
|
|
|
ClinVar: RCV000010968
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Lin et al. (1993) identified the insertion of 2 nucleotides (AA) resulting in a frameshift downstream from codon 1324 in exon 14. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0173 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 4-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906452,
|
|
|
|
|
|
|
|
ClinVar: RCV000010969, RCV002490352
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Lin et al. (1993) identified the deletion of 4 nucleotides (TAGA) resulting in a frameshift downstream from codons 1355-6 in exon 14. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0174 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 1-BP INS, A, CODON 1414
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1360639935,
|
|
|
|
|
|
|
|
ClinVar: RCV000010970
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Higuchi et al. (1991) identified the insertion of 1 nucleotide (A) resulting in a frameshift downstream from codon 1395 in exon 14. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0175 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 5-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906453,
|
|
|
|
|
|
|
|
ClinVar: RCV000010971
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported in a patient with severe hemophilia A (306700) the deletion of 5 nucleotides (CTCTT) resulting in a frameshift downstream from codons 1412-4 in exon 14. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0176 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 4-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906454,
|
|
|
|
|
|
|
|
ClinVar: RCV000010972
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Naylor et al. (1993) identified the deletion of 4 nucleotides (AAGA) resulting in a frameshift downstream from codons 1422-5 in exon 14. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0177 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 1-BP INS, A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906455,
|
|
|
|
|
|
gnomAD: rs387906455,
|
|
|
|
|
|
ClinVar: RCV001807852, RCV002503301, RCV003104145
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) identified in 2 patients with severe hemophilia A (306700) the insertion of 1 nucleotide (A) between codons 1458 and 1460 in exon 14 resulting in a frameshift. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0178 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 1-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906455,
|
|
|
|
|
|
gnomAD: rs387906455,
|
|
|
|
|
|
ClinVar: RCV000010974
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 patients with severe hemophilia A (306700), Higuchi et al. (1991) and Naylor et al. (1993) identified the deletion of 1 nucleotide (A) resulting in a frameshift downstream from codons 1439, 1440 or 1441 in exon 14. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0179 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 2-BP DEL, GA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2124048199,
|
|
|
|
|
|
|
|
ClinVar: RCV000010975
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Higuchi et al. (1991) identified the deletion of 2 nucleotides (GA) between codons 1555 and 1556 in exon 14 resulting in a frameshift. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0180 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 1-BP INS, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397514036,
|
|
|
|
|
|
|
|
ClinVar: RCV000010976, RCV003103984
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Lin et al. (1993) identified the insertion of 1 nucleotide (A) resulting in a frameshift downstream from codon 1590 in exon 14. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0181 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 1-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906456,
|
|
|
|
|
|
|
|
ClinVar: RCV000010977
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700), Lin et al. (1993) identified the deletion of 1 nucleotide (C) resulting in a frameshift downstream from codon 1601 in exon 14. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0182 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLU161TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852438,
|
|
|
|
|
|
|
|
ClinVar: RCV000010978
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with hemophilia A (306700), Lavergne et al. (1992) identified the substitution of GAG-to-TAG at codon 1615 in exon 14, resulting in a stop codon. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0183 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG1689HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs111033614,
|
|
|
|
|
|
gnomAD: rs111033614,
|
|
|
|
|
|
ClinVar: RCV000010979, RCV000851813, RCV001091839, RCV003914826
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Schwaab et al. (1993) found this mutation in 3 patients with 7-11% factor VIII activity, 130-165% factor VIII antigen, and mild hemophilia A (306700). The mutation is caused by a CGC-to-CAC transition at codon 1689 in exon 14 of the A3 domain, resulting in histidine for arginine-1689. The G-to-A transition follows the rule of CG-to-CA mutations at CG dinucleotides. The mutation has been shown to abolish normal cleavage by thrombin at the light chain. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0184 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG1696TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852439,
|
|
|
|
|
|
|
|
ClinVar: RCV000010980
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 patients with hemophilia A (306700) and inhibitors, Pattinson et al. (1990) identified the substitution of CGA to TGA at codon 1696 in exon 14, resulting in a stop codon. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. This mutation has also been found by others (Naylor et al., 1993). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0185 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG1696GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852439,
|
|
|
|
|
|
|
|
ClinVar: RCV000010981, RCV003114183
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Reiner and Thompson (1992) found this mutation in a patient with 17% factor VIII activity and mild hemophilia A (306700). The mutation was caused by a CGA-to-TGA transition at codon 1696 in exon 14 of the A3 domain, resulting in glycine for arginine-1696. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0186 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, IVS14AS, A-G, -2
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2073039685,
|
|
|
|
|
|
|
|
ClinVar: RCV000010982
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with less than 1% factor VIII activity, less than 2.5% factor VIII antigen, and severe hemophilia A (306700), Antonarakis et al. (1995) reported the substitution of A to G at the second nucleotide of the acceptor splice site of intron 14, resulting in abnormal splicing. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0187 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLY1769ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852440,
|
|
|
|
|
|
|
|
ClinVar: RCV000010983
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in 4 patients with 21-26% factor VIII activity, 14.5-26% factor VIII antigen, and mild hemophilia A (306700). The mutation was caused by a GGA-to-AGA transition at codon 1750 in exon 15 of the A3 domain, resulting in arginine for glycine-1750. Including the 19-amino acid signal peptide of the F8 gene (Vehar et al., 1984), this mutation is designated gly1769-to-arg (G1769R). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0188 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, LEU1756VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28937287,
|
|
|
|
|
|
|
|
ClinVar: RCV000010984
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with 5% factor VIII activity, 1.5% factor VIII antigen, and moderate hemophilia A (306700). The mutation was caused by a TTG-to-GTG transversion at codon 1756 in exon 15 of the A3 domain, resulting in valine for leucine-1756. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0189 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, LEU1775PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852441,
|
|
|
|
|
|
|
|
ClinVar: RCV000010985
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with 18.5% factor VIII activity, and mild hemophilia A (306700). The mutation was caused by a TTG-to-TTC transversion at codon 1756 in exon 15 of the A3 domain, resulting in phenylalanine for leucine-1756. Including the 19-amino acid signal peptide of the F8 gene (Vehar et al., 1984), this mutation is designated leu1775-to-phe (L1775F). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0190 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLY1760GLU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28937289,
|
|
|
|
|
|
|
|
ClinVar: RCV000010986
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Lin et al. (1993) found this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (306700). The mutation was caused by a GGG-to-GAG transition at codon 1760 in exon 15 of the A3 domain, resulting in glutamic acid for glycine-1760. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0191 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG1781HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852442,
|
|
|
|
|
|
|
|
ClinVar: RCV000010987, RCV001552643, RCV003430635
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in 4 patients with 2-2.5% factor VIII activity, 4.7-5.4% factor VIII antigen, and moderate hemophilia A (306700). The mutation was caused by a CGT-to-CAT transition at codon 1781 in exon 16 of the A3 domain, resulting in histidine for arginine-1781. The G-to-A transition follows the rule of CG-to-CA mutations at CG dinucleotides. See also Antonarakis et al. (1995). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0192 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG1781CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852443,
|
|
|
|
|
|
gnomAD: rs137852443,
|
|
|
|
|
|
ClinVar: RCV000010988
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Jonsdottir et al. (1992) found this mutation in a patient with 4-7% factor VIII activity and mild hemophilia A (306700). The mutation was caused by a CGT-to-TGT transition at codon 1781 in exon 16 of the A3 domain, resulting in cysteine for arginine-1781. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0193 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG1781GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852443,
|
|
|
|
|
|
gnomAD: rs137852443,
|
|
|
|
|
|
ClinVar: RCV000010989
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with 6% factor VIII activity and mild hemophilia A (306700). The mutation was caused by a CGT-to-GGT transversion at codon 1781 in exon 16 of the A3 domain, resulting in glycine for arginine-1781. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0194 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, SER1784TYR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852444,
|
|
|
|
|
|
|
|
ClinVar: RCV000010990
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in a patient with less than 1% factor VIII activity and clinically a severe hemophilia A (306700). The mutation was caused by a TCC-to-TAC transversion at codon 1784 in exon 16 of the A3 domain, resulting in tyrosine for serine-1784. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0195 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, LEU1789PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852445,
|
|
|
|
|
|
|
|
ClinVar: RCV000010991
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Diamond et al. (1992) and Lin et al. (1993) found this mutation in 3 patients with 7.2% factor VIII activity and mild hemophilia A (306700). The mutation was caused by a CTT-to-TTT transition at codon 1789 in exon 16 of the A3 domain, resulting in phenylalanine for leucine-1789. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0196 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLN1796TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852446,
|
|
|
|
|
|
|
|
ClinVar: RCV000010992
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with hemophilia A (306700) and inhibitors, Lin et al. (1993) identified the substitution of CAG-to-TAG at codon 1796 in exon 16, resulting in a stop codon. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0197 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, MET1823ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933674,
|
|
|
|
|
|
|
|
ClinVar: RCV000010993
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Lin et al. (1993) found this mutation in a patient with 4.6% factor VIII activity and moderate hemophilia A (306700). The mutation is caused by an ATG-to-ATA transition at codon 1823 in exon 16 of the A3 domain, resulting in isoleucine for methionine-1823. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0198 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, PRO1825SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933675,
|
|
|
|
|
|
|
|
ClinVar: RCV000010994, RCV000851817
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in a patient with 15% factor VIII activity and mild hemophilia A (306700). The mutation was caused by a CCC-to-TCC transition at codon 1825 in exon 16 of the A3 domain, resulting in serine for proline-1825. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0199 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, THR1826PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933676,
|
|
|
|
|
|
|
|
ClinVar: RCV000010995
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Economou et al. (1992) found this mutation in a patient with mild hemophilia A (306700). The mutation was caused by an ACT-to-CCT transversion at codon 1826 in exon 16 of the A3 domain, resulting in proline for threonine-1826. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0200 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, LYS1827TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906457,
|
|
|
|
|
|
|
|
ClinVar: RCV000010996
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 patients with hemophilia A (306700) and inhibitors, Lin et al. (1993) identified the mutation AAA to TAA at codon 1827 in exon 16, resulting in a stop codon. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0201 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ALA1834VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933677,
|
|
|
|
|
|
|
|
ClinVar: RCV000010997
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Lin et al. (1993) found this mutation in a patient with 18% factor VIII activity and mild hemophilia A (306700). The mutation was caused by a GCC-to-GTC transition at codon 1834 in exon 16 of the A3 domain, resulting in valine for alanine-1834. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0202 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, IVS16DS, G-A, -1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2123997676,
|
|
|
|
|
|
|
|
ClinVar: RCV000010998
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 patients with 9-18% factor VIII activity, 5.9% factor VIII antigen, and mild hemophilia A (306700), Higuchi et al. (1991) and Antonarakis et al. (1995) reported a G-to-A substitution at the -1 nucleotide of the donor splice site of intron 16, resulting in abnormal splicing. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0203 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ASP1846ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933678,
|
|
|
|
|
|
|
|
ClinVar: RCV000010999
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (306700). The mutation was caused by a GAT-to-AAT transition at codon 1846 in exon 17 of the A3 domain, resulting in asparagine for aspartic acid-1846. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0204 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ASP1846TYR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933678,
|
|
|
|
|
|
|
|
ClinVar: RCV000011000
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (306700). The mutation was caused by a GAT-to-TAT transversion at codon 1846 in exon 17 of the A3 domain, resulting in tyrosine for aspartic acid-1846. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0205 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, HIS1848ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933679,
|
|
|
|
|
|
|
|
ClinVar: RCV000011001, RCV003480027
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in a patient with 1-5% factor VIII activity and moderate hemophilia A (306700). The mutation was caused by a CAC-to-CGC transition at codon 1848 in exon 17 of the A3 domain, resulting in arginine for histidine-1848. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0206 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, PRO1854ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933680,
|
|
|
|
|
|
|
|
ClinVar: RCV000011002
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (306700). The mutation was caused by a CCC-to-CGC transversion at codon 1854 in exon 17 of the A3 domain, resulting in arginine for proline-1854. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0207 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 1-BP INS, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906458,
|
|
|
|
|
|
|
|
ClinVar: RCV000011003
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported in 1 patient with severe hemophilia A (306700) the insertion of 1 nucleotide (T) resulting in a frameshift downstream from codon 1855 in exon 17. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0208 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLN1874TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852448,
|
|
|
|
|
|
|
|
ClinVar: RCV000011004
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 1 patient with hemophilia A (306700) and inhibitors, Naylor et al. (1993) identified the substitution of CAG-to-TAG at codon 1874 in exon 17, resulting in a stop codon. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0209 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLU1885LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933681,
|
|
|
|
|
|
|
|
ClinVar: RCV000011005
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Lin et al. (1993) found this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (306700). The mutation was caused by a GAG-to-AAG transition at codon 1885 in exon 17 of the A3 domain, resulting in lysine for glutamic acid-1885. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0210 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 1-BP INS, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906459,
|
|
|
|
|
|
|
|
ClinVar: RCV000011006
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) identified in 1 patient with severe hemophilia A (306700) the insertion of 1 nucleotide (A) at codon 1907 in exon resulting in a frameshift. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0211 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ASN1922SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933682,
|
|
|
|
|
|
|
|
ClinVar: RCV000011007, RCV004791214
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) and Diamond et al. (1992) identified this mutation in 2 patients with less than 1% factor VIII activity and severe-to-moderate hemophilia A (306700). The mutation was an AAT-to-AGT transition at codon 1922 in exon 18 of the F8 gene, resulting in an asn1922-to-ser (N1922S) substitution in the A3 domain of the protein. </p><p>Summers et al. (2011) noted that N1922 lies at the interface of 2 A3 subdomains in F8 and that the A3 and adjacent C1 domains form an extensive hydrophobic interface. By expression in baby hamster kidney cells, they found that F8 with the N1922S mutation (F8-N1922S) was weakly secreted compared with wildtype F8, although secreted F8-N1922S showed normal or near-normal activity. Wildtype F8 followed the classic secretory pathway; however, F8-N1922S was delayed in the endoplasmic reticulum (ER), prior to processing and packaging in the Golgi. Use of conformation-specific monoclonal antibodies revealed that the delay in the ER was due to a defect in folding of the A3 domain and the adjacent C1 domain. Summers et al. (2011) concluded that the N1922S substitution results in poor secretion of a functional protein. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0212 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG1941LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28937294,
|
|
|
|
|
|
|
|
ClinVar: RCV000011008
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Nafa et al. (1992) found this mutation in a patient with 7% factor VIII activity and moderate hemophilia A (306700). The mutation was caused by a CGA-to-CTA transversion at codon 1941 in exon 18 of the A3 domain, resulting in leucine for arginine-1941. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0213 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, TRP1961TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852449,
|
|
|
|
|
|
|
|
ClinVar: RCV000011009
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with hemophilia A (306700), Lin et al. (1993) identified the substitution of TGG-to-TAG at codon 1942 in exon 18, resulting in a stop codon. Including the 19-amino acid signal peptide of the F8 gene (Vehar et al., 1984), this mutation is designated trp1961-to-ter (W1961X). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0214 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLY1948ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs111033615,
|
|
|
|
|
|
|
|
ClinVar: RCV000011010
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>David et al. (1994) found this mutation in a patient with 7.4% factor VIII activity, 46.7% factor VIII antigen, and moderate hemophilia A (306700). The mutation was caused by a GGC-to-GAC transition at codon 1948 in exon 18 of the A3 domain, resulting in aspartic acid for glycine-1948. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0215 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLY1960VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852450,
|
|
|
|
|
|
|
|
ClinVar: RCV000011011
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with 6% factor VIII activity and moderate hemophilia A (306700). The mutation was caused by a GGA-to-GTA transversion at codon 1960 in exon 18 of the A3 domain, resulting in valine for glycine-1960. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0216 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, HIS1961TYR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852451,
|
|
|
|
|
|
|
|
ClinVar: RCV000011012
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with 15.5% factor VIII activity, 7.8% factor VIII antigen, and mild hemophilia A (306700). The mutation was caused by a CAT-to-TAT transition at codon 1961 in exon 18 of the A3 domain, resulting in tyrosine for histidine-1961. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0217 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG1966TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852452,
|
|
|
|
|
|
|
|
ClinVar: RCV000011013
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 7 patients with hemophilia A (306700) (3 with inhibitors), Reiner and Thompson (1992) identified the mutation of CGA to TGA at codon 1966 in exon 18, resulting in a stop codon. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. This mutation has also been found by others (Lin et al., 1993; Naylor et al., 1993; Schwaab et al., 1993; and David et al., 1994). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0218 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 1-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906460,
|
|
|
|
|
|
gnomAD: rs387906460,
|
|
|
|
|
|
ClinVar: RCV000011014
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) identified in 2 patients with severe hemophilia A (306700) the deletion of 1 nucleotide (A) resulting in a frameshift downstream from codon 1967-1968 in exon 19. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0219 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 1-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906461,
|
|
|
|
|
|
|
|
ClinVar: RCV000011015
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported in 1 patient with severe hemophilia A (306700) the deletion of 1 nucleotide (G) resulting in a frameshift downstream from codon 1998 in exon 19. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0220 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLU1987TER, EX19DEL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267606791,
|
|
|
|
|
|
|
|
ClinVar: RCV000011016
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 1 patient with hemophilia A (306700), Naylor et al. (1993) identified the mutation of GAA to TAA at codon 1987 in exon 19, resulting in a stop codon and exon 19 skipping. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0221 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG1997TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852453,
|
|
|
|
|
|
|
|
ClinVar: RCV000011017
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) and Antonarakis et al. (1995) reported this mutation in 3 patients with less than 1-3.4% factor VIII activity and moderate to severe hemophilia A (306700). The mutation was caused by a CGG-to-TGG transition at codon 1997 in exon 19 of the A3 domain, resulting in tryptophan for arginine-1997. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0222 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ASN2019SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852454,
|
|
|
|
|
|
|
|
ClinVar: RCV000011018
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with 5% factor VIII activity, 3.3% factor VIII antigen, and moderate hemophilia A (306700). The mutation was caused by a AAT-to-AGT transition at codon 2019 in exon 19 of the A3 domain, resulting in serine for asparagine-2019. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0223 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, TRP2065ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852455,
|
|
|
|
|
|
|
|
ClinVar: RCV000011019
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Diamond et al. (1992) found this mutation in a patient with moderate hemophilia A (306700). The mutation was caused by a TGG-to-CGG transition at codon 2046 in exon 21 of the C1 domain, resulting in arginine for tryptophan-2046. Including the 19-amino acid signal peptide of the F8 gene (Vehar et al., 1984), this mutation is designated trp2065-to-arg (W2065R). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0224 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, SER2069PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852456,
|
|
|
|
|
|
|
|
ClinVar: RCV000011020
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (306700). The mutation was caused by a TCT-to-TTT transition at codon 2069 in exon 21 of the C1 domain, resulting in phenylalanine for serine-2069. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0225 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ASP2074GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852457,
|
|
|
|
|
|
|
|
ClinVar: RCV000011021
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) found this mutation in 2 patients with 4.5-9% factor VIII activity, 1.7-15.2% factor VIII antigen, and mild hemophilia A (306700). The mutation was caused by a GAT-to-GGT transition at codon 2074 in exon 22 of the C1 domain, resulting in glycine for aspartic acid-2074. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0226 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, PHE2120LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852458,
|
|
|
|
|
|
|
|
ClinVar: RCV000011022
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in 2 patients with 7-11% factor VIII activity, 5.3% factor VIII antigen, and mild hemophilia A (306700). The mutation was caused by a TTT-to-TTG transversion at codon 2101 in exon 22 of the C1 domain, resulting in leucine for phenylalanine-2101. Including the 19-amino acid signal peptide of the F8 gene (Vehar et al., 1984), this mutation is designated phe2120-to-leu (F2120L). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0227 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, TYR2124CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852459,
|
|
|
|
|
|
gnomAD: rs137852459,
|
|
|
|
|
|
ClinVar: RCV000011023, RCV001508071
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Naylor et al. (1993) found this mutation in a patient with 14% factor VIII activity and mild hemophilia A (306700). The mutation was caused by a TAT-to-TGT transition at codon 2105 in exon 22 of the C1 domain, resulting in cysteine for tyrosine-2105. Including the 19-amino acid signal peptide of the F8 gene (Vehar et al., 1984), this mutation is designated tyr2124-to-cys (Y2124C). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0228 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, SER2119TYR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852460,
|
|
|
|
|
|
|
|
ClinVar: RCV000011024
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in 3 patients with 3-8% factor VIII activity, 9.2-13.2% factor VIII antigen, and mild to moderate hemophilia A (306700). The mutation was caused by a TCC-to-TAC transversion at codon 2119 in exon 22 of the C1 domain, resulting in tyrosine for serine-2119. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0229 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 2-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906462,
|
|
|
|
|
|
|
|
ClinVar: RCV000011025
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) identified in 1 patient with severe hemophilia A (306700) the deletion of 2 nucleotides (TC) resulting in a frameshift downstream from serine-2119 in exon 22. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0230 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 2-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906463,
|
|
|
|
|
|
|
|
ClinVar: RCV000011026
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Tuddenham et al. (1991) identified in 1 patient with severe hemophilia A (306700) the deletion of 2 nucleotides (AA) resulting in a frameshift downstream from codon 2136 in exon 23. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0231 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG2169HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852461,
|
|
|
|
|
|
|
|
ClinVar: RCV000011028, RCV000851846, RCV003147281, RCV005049328
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) stated that this mutation had been reported in 10 patients with less than 1 to 7% factor VIII activity and severe to mild hemophilia A (306700). The mutation was caused by a CGT-to-CAT transition at codon 2150 in exon 23 of the C1 domain, resulting in histidine for arginine-2150. The G-to-A transition follows the rule of CG-to-CA mutations at CG dinucleotides. This mutation was reported by Higuchi et al. (1991), Naylor et al. (1993), Diamond et al. (1992); and Jonsdottir et al. (1992). Including the 19-amino acid signal peptide of the F8 gene (Vehar et al., 1984), this mutation is designated arg2169-to-his (R2169H). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0232 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, PRO2153GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852462,
|
|
|
|
|
|
|
|
ClinVar: RCV000011029
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with 3% factor VIII activity, 5.6% factor VIII antigen, and moderate hemophilia A (306700). The mutation was caused by a CCA-to-CAA transversion at codon 2153 in exon 23 of the C1 domain, resulting in glutamine for proline-2153. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0233 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, THR2154ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852463,
|
|
|
|
|
|
|
|
ClinVar: RCV000011030
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Jonsdottir et al. (1992) found this mutation in a patient with 6% factor VIII activity and mild hemophilia A (306700). The mutation was caused by an ACT-to-ATT transition at codon 2154 in exon 23 of the C1 domain, resulting in isoleucine for threonine-2154. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0234 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG2159CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852464,
|
|
|
|
|
|
|
|
ClinVar: RCV000011031, RCV003103985
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) stated that this mutation had been reported in 12 patients with 6 to 26% factor VIII activity, less than 5 to 15.7% factor VIII antigen, and mild hemophilia A (306700). The mutation was caused by a CGC-to-TGC transition at codon 2159 in exon 23 of the C1 domain, resulting in cysteine for arginine-2159. The mutation was reported by Higuchi et al. (1991), McGinniss et al. (1993); Diamond et al. (1992); and Jonsdottir et al. (1992). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0235 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG2159LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852465,
|
|
|
|
|
|
gnomAD: rs137852465,
|
|
|
|
|
|
ClinVar: RCV000011027
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with 12% factor VIII activity, 4.8% factor VIII antigen, and mild hemophilia A (306700). The mutation was caused by a CGC-to-CTC transversion at codon 2159 in exon 23 of the C1 domain, resulting in leucine for arginine-2159. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0236 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG2159HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852465,
|
|
|
|
|
|
gnomAD: rs137852465,
|
|
|
|
|
|
ClinVar: RCV000011032, RCV000852179, RCV003114184
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with 22% factor VIII activity, 11.9% factor VIII antigen, and mild hemophilia A (306700). The mutation was caused by a CGC-to-CAC transition at codon 2159 in exon 23 of the C1 domain, resulting in histidine for arginine-2159. The G-to-A transition follows the rule of CG-to-CA mutations at CG dinucleotides. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0237 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG2163HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852466,
|
|
|
|
|
|
|
|
ClinVar: RCV000011033, RCV004821959
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in 2 patients with 5% factor VIII antigen and moderate hemophilia A (306700). The mutation was caused by a CGC-to-CAC transition at codon 2163 in exon 23 of the C1 domain, resulting in histidine for arginine-2163. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0238 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG2163CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852467,
|
|
|
|
|
|
gnomAD: rs137852467,
|
|
|
|
|
|
ClinVar: RCV000011034, RCV002247323
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Reiner et al. (1992) found this mutation in a patient with 1% factor VIII activity, less than 10% factor VIII antigen, and moderate hemophilia A (306700). The mutation was caused by a CGC-to-TGC transition at codon 2163 in exon 23 of the C1 domain, resulting in cysteine for arginine-2163. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0239 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ALA2192PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852468,
|
|
|
|
|
|
|
|
ClinVar: RCV000011035
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Lin et al. (1993) found this mutation in a patient with 1% factor VIII activity and moderate hemophilia A (306700). The mutation was caused by a GCT-to-CCT transversion at codon 2192 in exon 24 of the C2 domain, resulting in proline for alanine-2192. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0240 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 3-BP DEL, PRO220 DEL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1229477261,
|
|
|
|
|
|
|
|
ClinVar: RCV000011036
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 patients with less than 1% factor VIII activity and severe-to-moderate hemophilia A (306700), Economou et al. (1992) and Lin et al. (1993) identified an in-frame deletion of 3-bp corresponding to codon 2205 (TctcCT) in exon 24 of the C2 domain, resulting in the deletion of proline-2205. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0241 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG2209LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852358,
|
|
|
|
|
|
|
|
ClinVar: RCV000011037
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Millar et al. (1991) found this mutation in a patient with 3% factor VIII activity, 2.5% factor VIII antigen, and moderate hemophilia A (306700). The mutation was caused by a CGA-to-CTA transversion at codon 2209 in exon 24 of the C2 domain, resulting in leucine for arginine-2209. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0242 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG2209GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852355,
|
|
|
|
|
|
|
|
ClinVar: RCV000011038
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with less than 1% factor VIII activity and severe hemophilia A (306700). The mutation was caused by a CGA-to-GGA transversion at codon 2209 in exon 24 of the C2 domain, resulting in glycine for arginine-2209. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0243 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 1-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906464,
|
|
|
|
|
|
|
|
ClinVar: RCV000011039
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported in 1 patient with severe hemophilia A (306700) the deletion of 1 nucleotide (G) resulting in a frameshift downstream from codon 2214 in exon 24. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0244 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, TRP2248CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852469,
|
|
|
|
|
|
|
|
ClinVar: RCV000011040, RCV000851849, RCV003114185
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Naylor et al. (1991) and Diamond et al. (1992) found this mutation in 2 patients with 3% factor VIII activity, moderate hemophilia A (306700), and inhibitors in 1 out of the 2. The mutation was caused by a TGG-to-TGT transversion at codon 2229 in exon 25 of the C2 domain, resulting in cysteine for tryptophan-2229. Including the 19-amino acid signal peptide of the F8 gene (Vehar et al., 1984), this mutation is designated trp2248-to-cys (W2248C). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0245 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLN2246ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852470,
|
|
|
|
|
|
|
|
ClinVar: RCV000011041, RCV001701638
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with 4.5% factor VIII activity, 1.1% factor VIII antigen, and moderate hemophilia A (306700). The mutation was caused by a CAG-to-CGG transition at codon 2246 in exon 25 of the C2 domain, resulting in arginine for glutamine-2246. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0246 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 2-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906465,
|
|
|
|
|
|
|
|
ClinVar: RCV000011042
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Lin et al. (1993) identified in 1 patient with severe hemophilia A (306700) the deletion of 2 nucleotides (AG) resulting in a frameshift downstream from glutamine-2246 in exon 25. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0247 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, GLN2270TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852471,
|
|
|
|
|
|
|
|
ClinVar: RCV000011043
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 1 patient with hemophilia A (306700), Antonarakis et al. (1995) reported the mutation of CAG-to-TAG at codon 2270 in exon 25, resulting in a stop codon. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0248 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 5-BP DEL, FS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906466,
|
|
|
|
|
|
|
|
ClinVar: RCV000011044
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported in 1 patient with severe hemophilia A (306700) the deletion of 5 nucleotides (AAATC) resulting in a frameshift downstream from codon 2285-86 or 87 in exon 26. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0249 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, PRO2300LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852472,
|
|
|
|
|
|
|
|
ClinVar: RCV000011045, RCV000851613, RCV001701721
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) found this mutation in a patient with 7.5% factor VIII activity and mild hemophilia A (306700). The mutation was caused by a CCG-to-CTG transition at codon 2300 in exon 26 of the C2 domain, resulting in leucine for proline-2300. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0250 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG2304CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852473,
|
|
|
|
|
|
gnomAD: rs137852473,
|
|
|
|
|
|
ClinVar: RCV000011046
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Higuchi et al. (1991) and Reiner et al. (1992) found this mutation in 2 patients with less than 1% factor VIII activity, less than 10% factor VIII antigen, and severe hemophilia A (306700). The mutation was caused by a CGC-to-TGC transition at codon 2304 in exon 26 of the C2 domain, resulting in cysteine for arginine-2304. The C-to-T transition follows the rule of CG-to-TG mutations at CG dinucleotides. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0251 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, ARG2304HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852474,
|
|
|
|
|
|
|
|
ClinVar: RCV000011047
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported this mutation in a patient with mild hemophilia A (306700). The mutation was caused by a CGC-to-CAC transition at codon 2304 in exon 26 of the C2 domain, resulting in histidine for arginine-2304. The G-to-A transition follows the rule of CG-to-CA mutations at CG dinucleotides. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0252 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX1-6DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011048
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) (patient H238) and factor VIII inhibitors, Millar et al. (1990) found a deletion of exons 1-6 of the factor VIII gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0253 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX2-4DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011049
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) (patient TWN11) and factor VIII inhibitors, Lin et al. (1993) found a deletion of exons 2-4 of the factor VIII gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0254 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX3-5DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011050
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) (patient H151), Millar et al. (1990) found a deletion of exons 3-5 of the factor VIII gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0255 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX4-10DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011051
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) (patient TWN27) and factor VIII inhibitors, Lin et al. (1993) found a deletion of exons 4-10 of the factor VIII gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0256 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX5-13DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011052
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) (patient H571) and factor VIII inhibitors, Millar et al. (1990) found a deletion of exons 5-13 of the factor VIII gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0257 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX10DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011053
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) (patient 149), Krepelova et al. (1992) found a deletion of exon 10 of the factor VIII gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0258 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX14-21DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011054
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) (patient H229) and factor VIII inhibitors, Millar et al. (1990) found a deletion of exons 14-21 of the factor VIII gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0259 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX14-22DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011055
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) (patient H20) and factor VIII inhibitors, Nafa et al. (1990) found a deletion of exons 14-22 of the factor VIII gene. See also Antonarakis et al. (1995). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0260 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX15-22DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011056
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Antonarakis et al. (1995) reported 3 patients with severe hemophilia A (306700) who had a deletion of exons 15-22 of the factor VIII gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0261 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX16-26DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011057
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) (patient HDX3) and factor VIII inhibitors, Figueiredo et al. (1992) found a deletion of exons 16-26 of the factor VIII gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0262 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX18-19DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011058
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) (patient 5b), Grover et al. (1987) found a deletion of exons 18-19 of the factor VIII gene. This deletion may extend to exon 22. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0263 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX16DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011059
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) (patient HD10), Schwaab et al. (1993) found a deletion of exon 16 of the factor VIII gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0264 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX19-21DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011060
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) (patient H58) and factor VIII inhibitors, Millar et al. (1990) found a deletion of exons 19-21 of the factor VIII gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0265 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX23-24DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011061
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) (patient HA711), Lavergne et al. (1992) found a deletion of exons 23-24 of the factor VIII gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0266 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, EX23-26DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011062
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia A (306700) (patient HDX2) and factor VIII inhibitors, Din et al. (1986) found a deletion of exons 23-26 of the factor VIII gene. See also Lavergne et al. (1992). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0267 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, 1-BP DEL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2124094327,
|
|
|
|
|
|
|
|
ClinVar: RCV000011063
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Favier et al. (2000) described a 14-month-old girl with severe hemophilia A (306700). Both of her parents had normal values of factor VIII activity, and von Willebrand disease was excluded. Karyotype analysis demonstrated no obvious alteration, and no F8 gene inversions were found. Direct sequencing of the F8 gene exons revealed a frameshift-stop mutation (Q565delC/ter566) in the heterozygous state in the proposita only. F8 gene polymorphism analysis indicated that the mutation must have occurred de novo in the paternal germline. Furthermore, analysis of the pattern of X chromosome methylation at the human androgen receptor gene locus demonstrated a skewed inactivation of the derived maternal X chromosome from the lymphocytes of the proband's DNA. Thus, the severe hemophilia A in the proposita resulted from a de novo F8 gene mutation on the paternally derived X chromosome, associated with a nonrandom pattern of inactivation of the maternally derived X chromosome. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0268 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, CYS179GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852475,
|
|
|
|
|
|
|
|
ClinVar: RCV000011064
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 brothers with severe hemophilia A (306700), Mazurier et al. (2002) found a T-to-G transversion in exon 4 of the F8C gene, resulting in a cys179-to-gly (C179G) mutation. This mutation affected a cysteine residue in the A1 domain that is conserved in the sequences of the murine, canine, and swine factor 8 genes. A maternal first cousin showed factor VIII deficiency and bleeding, but was found instead to have von Willebrand disease type 2N (see 613554) due to compound heterozygous mutations in the VWF gene (613160.0035 and 613160.0036). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0269 HEMOPHILIA A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F8, TYR16CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852476,
|
|
|
|
|
|
|
|
ClinVar: RCV000011065
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Valleix et al. (2002) described an A-to-G transition in exon 1 of the F8 gene in monozygotic twin females that caused a tyr16-to-cys (Y16C) mutation. Both twins were heterozygous for the mutation, which caused severe hemophilia A (306700) in 1 and mild phenotype in the other. The mutation was not present in the twins' healthy sister or parents, suggesting that it had occurred de novo in the germline of 1 parent. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0270 HEMOPHILIA A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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F8, ALU INS
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<br />
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ClinVar: RCV000011066
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Sukarova et al. (2001) described a family with a severe form of hemophilia A (306700) in which they identified an Alu retrotransposition event in a coding exon, which represented the first report of an Alu insertion in the F8 gene. The propositus was an 18-year-old Bulgarian boy in whom the diagnosis of severe hemophilia had been made at the age of 1 year. His 12-year-old brother was also affected. There was no other family history of the disorder. The 341-bp element incorporated into the F8C gene interrupted the reading frame of the mature protein at met1224, resulting in a stop codon within the inserted sequence. Sequence analysis showed that the inserted fragment was a full Alu repeat belonging to the Yb8 subfamily of Alu repetitive sequences, according to the standardized nomenclature for Alu repeats (Batzer et al., 1996). The mutation site was flanked by a 5-bp (AAGAA) direct repeat which Sukarova et al. (2001) stated was the shortest direct repeat described at the integration points of Alu insertions. </p><p>Ganguly et al. (2003) reported a second instance: a 6-year-old male in whom an Alu element was inserted at position -19 of intron 18 of the F8C gene, causing skipping of exon 19 and hemophilia A. The insertion, which did not affect the natural splice donor site, was in the opposite orientation with respect to the direction of transcription of the F8 gene. The size of intron 18 was predicted to be increased by approximately 331 nucleotides because of the insertion. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0271 HEMOPHILIA A, MILD</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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F8, 2113+461_2113+473DEL
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<br />
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SNP: rs781928603,
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gnomAD: rs781928603,
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ClinVar: RCV000591635, RCV002248811
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 unrelated probands with mild hemophilia A (HEMA; 306700), Jourdy et al. (2018) identified an intronic deletion (c.2113+461_2113+473del, NM_000132.3) in intron 13 of the F8 gene. Transcription analysis of patient cells showed an aberrant transcript resulting from this deletion; it caused the insertion of a 122-bp intronic fragment (c.2113_2114ins2113+477_2113+598) at the exon 13-14 junction. This out-of-frame insertion was predicted to result in a truncated protein (Gly705AspfsTer37). DNA sequencing analysis showed that the included pseudoexon corresponds to an antisense AluY element, and that the deletion removed a part of the poly(T)-tail from the right arm of AluY. The findings suggested aberrant exonization of the AluY element that likely resulted from decreased binding of the cryptic exon silencer HNRNPC (164020). Disruption of or siRNA-mediated knockdown of HNRNPC in HeLa cells reproduced the effect of the deletion. Screening of 992 unrelated French families with mild hemophilia A found a deletion in the poly(T)-tail of AluY in intron 13 in 6.1% of families, although these resulted from several different intronic deletions in this region, suggesting a recurring molecular mechanism. Haplotype analysis suggested a founder effect for c.2113+461_2113+473del. The patients also carried a normal F8 transcript in addition to the aberrant transcript, explaining the mild phenotype. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0272 THROMBOPHILIA, X-LINKED, DUE TO FACTOR VIII DEFECT</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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F8, 23.4-KB DUP
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<br />
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ClinVar: RCV004560336
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 7 individuals from 2 Italian families with thrombophilia due to factor VIII defect (THPH13; 301071), Simioni et al. (2021) identified a 23.4-kb tandem duplication in the F8 gene, including the promoter, exon 1, and part of intron 1. The mutation was hemizygous in affected males and heterozygous in affected females. The mutation was found by a combination of linkage analysis, MLPA analysis, whole-genome sequencing, and Sanger sequencing. The mutation segregated with disease in both families. The variant was not present in the 1000 Genomes Project database or in 103 control individuals. F8 mRNA was increased in patient lymphocytes. Increased transcriptional activity of fragments of the duplicated region was demonstrated via luciferase assay. The authors designated this mutation 'FVIII Padua.' </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>See Also:</strong>
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</span>
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</h4>
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<span class="mim-text-font">
|
|
Aly et al. (1992); Barrow and Graham (1973); Bloom and Peake (1977);
|
|
Gitschier et al. (1985); Graham et al. (1985); Gralnick and Coller
|
|
(1976); Green et al. (1991); Hoyer (1981); Jaffe and Nachman (1975);
|
|
Janco et al. (1987); Lawn (1985); Marchesi et al. (1972); Nilsson et
|
|
al. (1966); Oberle et al. (1985); Peake et al. (1985); Pratt et al.
|
|
(1999); Ratnoff (1978); Roberts (1971); Saiki et al. (1985);
|
|
Tuddenham et al. (1981); Woolf (1962); Youssoufian et al. (1987);
|
|
Youssoufian et al. (1988)
|
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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Abrams, E. S., Murdaugh, S. E., Lerman, L. S.
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<strong>Comprehensive detection of single base changes in human genomic DNA using denaturing gradient gel electrophoresis and a GC clamp.</strong>
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Genomics 7: 463-475, 1990.
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Acquila, M., Caprino, D., Pecorara, M., Baudo, F., Morfini, M., Mori, P. G.
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<strong>Two novel mutations at 373 codon of FVIII gene detected by DGGE.</strong>
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Aly, A. M., Arai, M., Hoyer, L. W.
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<strong>Cysteamine enhances the procoagulant activity of factor VIII-East Hartford, a dysfunctional protein due to a light chain thrombin cleavage site mutation (arginine-1689 to cysteine).</strong>
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J. Clin. Invest. 89: 1375-1381, 1992.
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<p class="mim-text-font">
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Aly, A. M., Higuchi, M., Kasper, C. K., Kazazian, H. H., Jr., Antonarakis, S. E., Hoyer, L. W.
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<strong>Hemophilia A due to mutations that create new N-glycosylation sites.</strong>
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Proc. Nat. Acad. Sci. 89: 4933-4937, 1992.
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[PubMed: 1594597]
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[Full Text: https://doi.org/10.1073/pnas.89.11.4933]
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<li>
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<p class="mim-text-font">
|
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Aly, A. M., Hoyer, L. W.
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<strong>Factor VIII-East Hartford (arginine1689 to cysteine) has procoagulant activity when separated from von Willebrand factor.</strong>
|
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J. Clin. Invest. 89: 1382-1387, 1992.
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[PubMed: 1569181]
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[Full Text: https://doi.org/10.1172/JCI115726]
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Antonarakis, S. E., Copeland, K. L., Carpenter, R. J., Jr., Carta, C. A., Hoyer, L. W., Caskey, C. T., Toole, J. J., Kazazian, H. H., Jr.
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<strong>Prenatal diagnosis of haemophilia A by factor VIII gene analysis.</strong>
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Lancet 325: 1407-1409, 1985. Note: Originally Volume I.
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Antonarakis, S. E., Kazazian, H. H., Tuddenham, G. D.
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<strong>Molecular etiology of factor VIII deficiency in hemophilia A.</strong>
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Hum. Mutat. 5: 1-22, 1995.
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Antonarakis, S. E., Rossiter, J. P., Young, M., Horst, J., de Moerloose, P., Sommer, S. S., Ketterling, R. P., Kazazian, H. H., Jr., Negrier, C., Vinciguerra, C., Gitschier, J., Goossens, M., and 54 others.
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<strong>Factor VIII inversions in severe hemophilia A: results from an international consortium.</strong>
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Blood 86: 2206-2212, 1995.
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[PubMed: 7662970]
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Antonarakis, S. E., Waber, P. G., Kittur, S. D., Patel, A. S., Kazazian, H. H., Jr., Mellis, M. A., Counts, R. B., Stamatoyannopoulos, G., Bowie, E. J. W., Fass, D. N., Pittman, D. D., Wozney, J. M., Toole, J. J.
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<strong>Hemophilia A: detection of molecular defects and of carriers by DNA analysis.</strong>
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New Eng. J. Med. 313: 842-848, 1985.
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Arai, M., Higuchi, M., Antonarakis, S. E., Kazazian, H. H., Jr., Phillips, J. A., III, Janco, R. L., Hoyer, L. W.
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<strong>Characterization of a thrombin cleavage site mutation (arg1689-to-cys) in the factor VIII gene of two unrelated patients with cross-reacting material-positive hemophilia A.</strong>
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Blood 75: 384-389, 1990.
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[PubMed: 2104766]
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Arai, M., Inaba, H., Higuchi, M., Antonarakis, S. E., Kazazian, H. H., Jr., Fujimaki, M., Hoyer, L. W.
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<strong>Direct characterization of factor VIII in plasma: detection of a mutation altering a thrombin cleavage site (arginine372-to-histidine).</strong>
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Proc. Nat. Acad. Sci. 86: 4277-4281, 1989.
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[PubMed: 2498882]
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Arveiler, B., Vincent, A., Mandel, J.-L.
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<strong>Toward a physical map of the Xq28 region in man: linking color vision, G6PD, and coagulation factor VIII genes to an X-Y homology region.</strong>
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Genomics 4: 460-471, 1989.
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Bardoni, B., Sampietro, M., Romano, M., Crapanzano, M., Mannucci, P. M., Camerino, G.
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<strong>Characterization of a partial deletion of the factor VIII gene in a haemophiliac with inhibitor.</strong>
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Hum. Genet. 79: 86-88, 1988.
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[PubMed: 2835307]
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<p class="mim-text-font">
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Barrow, E. M. S., Graham, J. B.
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<strong>Factor VIII. (Letter)</strong>
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Lancet 301: 1312-1313, 1973. Note: Originally Volume I.
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[PubMed: 4126092]
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[Full Text: https://doi.org/10.1016/s0140-6736(73)91319-6]
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Batzer, M. A., Deininger, P. L., Hellmann-Blumberg, U., Jurka, J., Labuda, D., Rubin, C. M., Schmid, C. W., Zietkiewicz, E., Zuckerkandl, E.
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<strong>Standardized nomenclature for Alu repeats.</strong>
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J. Molec. Evol. 42: 3-6, 1996.
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[PubMed: 8576960]
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</p>
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<p class="mim-text-font">
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Becker, J., Schwaab, R., Moller-Taube, A., Schwaab, U., Schmidt, W., Brackmann, H. H., Grimm, T., Olek, K., Oldenburg, J.
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<strong>Characterization of the factor VIII defect in 147 patients with sporadic hemophilia A: family studies indicate a mutation type-dependent sex ratio of mutation frequencies.</strong>
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Am. J. Hum. Genet. 58: 657-670, 1996.
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[PubMed: 8644728]
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<p class="mim-text-font">
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Berg, L.-P., Wieland, K., Millar, D. S., Schlosser, M., Wagner, M., Kakkar, V. V., Reiss, J., Cooper, D. N.
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<strong>Detection of a novel point mutation causing haemophilia A by PCR/direct sequencing of ectopically-transcribed factor VIII mRNA.</strong>
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Hum. Genet. 85: 655-658, 1990.
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[PubMed: 2121641]
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[Full Text: https://doi.org/10.1007/BF00193593]
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</p>
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<li>
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<p class="mim-text-font">
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Bernardi, F., Volinia, S., Patracchini, P., Gemmati, D., Boninsegna, S., Schwienbacher, C., Marchetti, G.
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<strong>A recurrent missense mutation (arg-to-gln) and a partial deletion in factor VIII gene causing severe haemophilia A.</strong>
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Brit. J. Haemat. 71: 271-276, 1989.
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|
|
|
[PubMed: 2493803]
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|
[Full Text: https://doi.org/10.1111/j.1365-2141.1989.tb04266.x]
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</p>
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<p class="mim-text-font">
|
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Bidichandani, S. I., Shiach, C. R., Lanyon, W. G., Connor, J. M.
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<strong>A novel splice donor mutation affecting position +3 in intron 6 of the factor VIII gene.</strong>
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Hum. Molec. Genet. 3: 651-653, 1994.
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|
|
[PubMed: 8069313]
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[Full Text: https://doi.org/10.1093/hmg/3.4.651]
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</p>
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<p class="mim-text-font">
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Bird, A. P.
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<strong>DNA methylation and the frequency of CpG in animal DNA.</strong>
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|
Nucleic Acids Res. 8: 1499-1504, 1980.
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[PubMed: 6253938]
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[Full Text: https://doi.org/10.1093/nar/8.7.1499]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Bloom, A. L., Peake, I. R.
|
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<strong>Molecular genetics of factor VIII and its disorders.</strong>
|
|
Semin. Hemat. 14: 319-339, 1977.
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[PubMed: 327558]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Briet, E., Bakker, B., Brocker-Vriends, A.
|
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<strong>Somatic and germinal mosaicism for a deletion in the factor VIII gene. (Abstract)</strong>
|
|
Brit. J. Haemat. 71 (suppl. 1): 1 only, 1989.
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Brinke, A., Tagliavacca, L., Naylor, J., Green, P., Giangrande, P., Giannelli, F.
|
|
<strong>Two chimaeric transcription units result from an inversion breaking intron 1 of the factor VIII gene and a region reportedly affected by reciprocal translocations in T-cell leukaemia.</strong>
|
|
Hum. Molec. Genet. 5: 1945-1951, 1996.
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|
[PubMed: 8968748]
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