19989 lines
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Entry
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- *300746 - COAGULATION FACTOR IX; F9
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- OMIM
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</form>
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*300746</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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<a href="#title"><strong>Title</strong></a>
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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="#geneFunction">Gene Function</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="#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="#animalModel">Animal Model</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/300746">Table View</a>
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</li>
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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>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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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=ENSG00000101981;t=ENST00000218099" 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=2158" 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=300746" 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=ENSG00000101981;t=ENST00000218099" 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_000133,NM_001313913,XM_005262397" 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_000133" 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=300746" 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://hprd.org/summary?hprd_id=02385&isoform_id=02385_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/F9" 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/180288,180553,182609,182611,182613,182621,182623,344471,412174,439774,490124,490126,545021,4261692,4469253,4503649,22385321,29469530,30841428,30841430,58737077,67476446,70610325,70610327,80478260,80479046,100017706,100017708,100017710,100017712,100017714,100017716,100017718,100017720,100017722,100017724,100017726,100017728,100017730,100017732,100017734,100017736,100017738,100017740,100017742,100017744,100017746,100017748,100017750,100017752,100017754,100017756,100017758,100017760,100017762,100017764,100017766,100017768,100017770,100017772,100017774,100017776,100017778,100017780,100017782,100017784,100017786,100017788,100017790,100017792,100017794,100017796,100017798,100017800,100017802,100017804,100017806,100017808,100017810,100017812,100017814,100017816,100017818,100017820,100017822,100017824,100017826,100017828,100017830,100017832,100017834,100017836,100017838,110623178,119608837,119608838,119608839,119608840,158258935,326684020,326684022,326684024,530422392,927028867,2050590094,2050590096,2050590098,2462628682" 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/P00740" 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=2158" 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=ENSG00000101981;t=ENST00000218099" 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=F9" 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=F9" 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+2158" 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/F9" 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:2158" 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/2158" 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=ENST00000218099.7&hgg_start=139530739&hgg_end=139563459&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">
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<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:3551" 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:3551" 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/f9" 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=300746[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=300746[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://gnomad.broadinstitute.org/gene/ENSG00000101981" 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=F9" 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=F9" 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=F9" 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="#mimLocusSpecificDBsFold" id="mimLocusSpecificDBsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A gene-specific database of variation."><span id="mimLocusSpecificDBsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Locus Specific DBs</div>
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<div id="mimLocusSpecificDBsFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="http://www.LOVD.nl/F9" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">F9 database at LOVD</a></div><div style="margin-left: 0.5em;"><a href="http://www.hemobase.com/en/Base_de_datos_HB.htm" title="F9 Mutation Registry at Hemobase" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">F9 Mutation Registry at He…</a></div><div style="margin-left: 0.5em;"><a href="http://www.kcl.ac.uk/ip/petergreen/haemBdatabase.html" title="Haemophilia B Mutation Database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Haemophilia B Mutation Dat…</a></div>
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</div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=F9&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/PA27954" 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:3551" 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:88384" 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/F9#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:88384" 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/2158/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/OMIA000438/" 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=2158" 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-030714-2" 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">
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<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:2158" 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=F9&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> 1336117005<br />
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">ICD+</a>
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</div>
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<div>
|
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
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300746
|
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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 IX; F9
|
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</span>
|
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</h3>
|
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</div>
|
|
<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
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<p>
|
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<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
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</p>
|
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</div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
FACTOR IX<br />
|
|
PLASMA THROMBOPLASTIN COMPONENT; PTC
|
|
</span>
|
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</h4>
|
|
</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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<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=F9" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">F9</a></em></strong>
|
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</span>
|
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</p>
|
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</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/739?start=-3&limit=10&highlight=739">Xq27.1</a>
|
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chrX:139530739-139563459&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:139,530,739-139,563,459</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<br />
|
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</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">
|
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<th>
|
|
Location
|
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</th>
|
|
<th>
|
|
Phenotype
|
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<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=300807,301052,306900,300807" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
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|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
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<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
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Xq27.1
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{Deep venous thrombosis, protection against}
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<a href="/entry/300807"> 300807 </a>
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<abbr class="mim-tip-hint" title="X-linked recessive">XLR</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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{Warfarin sensitivity}
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<a href="/entry/301052"> 301052 </a>
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<abbr class="mim-tip-hint" title="X-linked">XL</abbr>
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Hemophilia B
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<a href="/entry/306900"> 306900 </a>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="X-linked recessive">XLR</abbr>
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Thrombophilia 8, X-linked, due to factor IX defect
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<a href="/entry/300807"> 300807 </a>
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<abbr class="mim-tip-hint" title="X-linked recessive">XLR</abbr>
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<span class="mim-font">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/300746" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/300746" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<p>The F9 gene encodes coagulation factor IX, which circulates as an inactive zymogen until proteolytic release of its activation peptide allows it to assume the conformation of an active serine protease (<a href="#54" class="mim-tip-reference" title="Davie, E. W., Fujikawa, K. <strong>Basic mechanisms in blood coagulation.</strong> Ann. Rev. Biochem. 44: 799-829, 1975.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/237463/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">237463</a>] [<a href="https://doi.org/10.1146/annurev.bi.44.070175.004055" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="237463">Davie and Fujikawa, 1975</a>). Its role in the blood coagulation cascade is to activate factor X (F10; <a href="/entry/227600">227600</a>) through interactions with calcium, membrane phospholipids, and factor VIII (F8; <a href="/entry/300841">300841</a>). Factor IX and factor X both consist of 2 polypeptide chains referred to as the L (light) and H (heavy) chains. The H chain bears a structural resemblance to the polypeptide chain of the pancreatic serine protease trypsin (PRSS1; <a href="/entry/276000">276000</a>). The L chain is covalently linked to the H chain by a single disulfide bond (<a href="#62" class="mim-tip-reference" title="Fujikawa, K., Coan, M. H., Enfield, D. L., Titani, K., Ericsson, L. H., Davie, E. W. <strong>A comparison of bovine prothrombin, factor IX (Christmas factor), and factor X (Stuart factor).</strong> Proc. Nat. Acad. Sci. 71: 427-430, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4205592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4205592</a>] [<a href="https://doi.org/10.1073/pnas.71.2.427" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4205592">Fujikawa et al., 1974</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=237463+4205592" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="cloning" class="mim-anchor"></a>
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<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>Cloning and Expression</strong>
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<p><a href="#98" class="mim-tip-reference" title="Kurachi, K., Davie, E. W. <strong>Isolation and characterization of a cDNA coding for human factor IX.</strong> Proc. Nat. Acad. Sci. 79: 6461-6464, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6959130/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6959130</a>] [<a href="https://doi.org/10.1073/pnas.79.21.6461" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6959130">Kurachi and Davie (1982)</a> isolated and characterized a cDNA coding for the human factor IX gene. The deduced 416-residue protein contains a 46-residue leader sequence that includes both a signal sequence and a pro-sequence for the mature protein that circulates in plasma. The amino-terminal region contains 12 glutamic acid residues that are converted to gamma-carboxyglutamic acid in the mature protein. The arginyl peptide bonds that are cleaved in the conversion of human factor IX to factor IXa by factor XIa (F11; <a href="/entry/264900">264900</a>) were identified as Arg145-Ala146 and Arg180-Val181. The cleavage of these 2 internal peptide bonds results in the formation of a 35-residue activation peptide and factor IXa, a serine protease composed of a 145-residue light chain and a 236-residue heavy chain that are held together by a disulfide bond. The homology in the amino acid sequence between human and bovine factor IX was found to be 83%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6959130" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#44" class="mim-tip-reference" title="Choo, K. H., Gould, K. G., Rees, D. J. G., Brownlee, G. G. <strong>Molecular cloning of the gene for human anti-haemophilic factor IX.</strong> Nature 299: 178-180, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6287289/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6287289</a>] [<a href="https://doi.org/10.1038/299178a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6287289">Choo et al. (1982)</a> isolated clones corresponding to the human factor IX gene from a human cDNA library. The deduced human protein showed 78% homology with the bovine protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6287289" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#85" class="mim-tip-reference" title="Jagadeeswaran, P., Lavelle, D. E., Kaul, R., Mohandas, T., Warren, S. T. <strong>Isolation and characterization of human factor IX cDNA: identification of Taq I polymorphism and regional assignment.</strong> Somat. Cell Molec. Genet. 10: 465-473, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6089357/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6089357</a>] [<a href="https://doi.org/10.1007/BF01534851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6089357">Jagadeeswaran et al. (1984)</a> used the peptide sequence of bovine F9 to develop a probe to screen a human liver cDNA library. They identified a recombinant clone corresponding to 70% of the coding region of human factor IX. This F9 cDNA was used to probe restriction endonuclease digested polymorphism, as well as to verify that the haploid genome contains a single copy of the gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6089357" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#4" class="mim-tip-reference" title="Anson, D. S., Choo, K. H., Rees, D. J. G., Giannelli, F., Gould, K., Huddleston, J. A., Brownlee, G. G. <strong>The gene structure of human anti-haemophilic factor IX.</strong> EMBO J. 3: 1053-1060, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6329734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6329734</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1984.tb01926.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6329734">Anson et al. (1984)</a> isolated clones corresponding to the full sequence of the human factor IX gene from a human liver cDNA library. The gene encodes a mature 415-residue protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6329734" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>Gene Structure</strong>
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<p><a href="#4" class="mim-tip-reference" title="Anson, D. S., Choo, K. H., Rees, D. J. G., Giannelli, F., Gould, K., Huddleston, J. A., Brownlee, G. G. <strong>The gene structure of human anti-haemophilic factor IX.</strong> EMBO J. 3: 1053-1060, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6329734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6329734</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1984.tb01926.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6329734">Anson et al. (1984)</a> determined that the F9 gene contains 8 exons and spans about 34 kb. Introns accounted for 92% of the gene length. Exons conformed roughly to previously designated protein regions but the catalytic region of the protein appeared to be coded by 2 separate exons, which differed from the arrangement in other characterized serine protease genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6329734" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 IXa activates factor X as part of an intrinsic activating complex that also consists of factor VIIIa. Using several chimeric and mutant F9 proteins in coagulation assays, <a href="#175" class="mim-tip-reference" title="Wilkinson, F. H., London, F. S., Walsh, P. N. <strong>Residues 88-109 of factor IXa are important for assembly of the factor X activating complex.</strong> J. Biol. Chem. 277: 5725-5733, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11726655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11726655</a>] [<a href="https://doi.org/10.1074/jbc.M107027200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11726655">Wilkinson et al. (2002)</a> determined that residues 88 to 109, excluding arg94, within the second epidermal growth factor-like domain of factor IX are important for phospholipid surface assembly of the factor X activating complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11726655" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#135" class="mim-tip-reference" title="Rusconi, C. P., Scardino, E., Layzer, J., Pitoc, G. A., Ortel, T. L., Monroe, D., Sullenger, B. A. <strong>RNA aptamers as reversible antagonists of coagulation factor IXa.</strong> Nature 419: 90-94, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12214238/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12214238</a>] [<a href="https://doi.org/10.1038/nature00963" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12214238">Rusconi et al. (2002)</a> demonstrated that protein-binding oligonucleotides (aptamers) against coagulation factor IXa are potent anticoagulants. They also showed that oligonucleotides complementary to these aptamers could act as antidotes capable of efficiently reversing the activity of these new anticoagulants in plasma from healthy volunteers and from patients who cannot tolerate heparin. <a href="#135" class="mim-tip-reference" title="Rusconi, C. P., Scardino, E., Layzer, J., Pitoc, G. A., Ortel, T. L., Monroe, D., Sullenger, B. A. <strong>RNA aptamers as reversible antagonists of coagulation factor IXa.</strong> Nature 419: 90-94, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12214238/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12214238</a>] [<a href="https://doi.org/10.1038/nature00963" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12214238">Rusconi et al. (2002)</a> concluded that their strategy was generalizable for rationally designing a drug-antidote pair, thus opening the way for developing safer regulatable therapeutics. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12214238" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="#33" class="mim-tip-reference" title="Camerino, G., Mattei, M. G., Mattei, J. F., Jaye, M., Mandel, J. L. <strong>Genetics of the fragile X-mental retardation syndrome: close linkage to hemophilia B and transmission through a normal male.</strong> Nature 306: 701-704, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6689201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6689201</a>] [<a href="https://doi.org/10.1038/306701a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6689201">Camerino et al. (1983)</a> used a factor IX gene probe to demonstrate close linkage to the locus for fragile X syndrome (<a href="/entry/300624">300624</a>) (17 nonrecombinants, 0 recombinants; lod = 5.12 at theta = 0.0). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6689201" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#37" class="mim-tip-reference" title="Chance, P. F., Dyer, K. A., Kurachi, K., Yoshitake, S., Ropers, H.-H., Wieacker, P., Gartler, S. M. <strong>Regional localization of the human factor IX gene by molecular hybridization.</strong> Hum. Genet. 65: 207-208, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6686210/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6686210</a>] [<a href="https://doi.org/10.1007/BF00286666" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6686210">Chance et al. (1983)</a> assigned the human F9 gene to chromosome Xq27-qter using somatic cell hybridization. F9 was in a fragment of the X chromosome associated with no HPRT (<a href="/entry/308000">308000</a>) activity in the hybrid cell, suggesting that F9 is distal to HPRT. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6686210" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Using a cDNA probe in the study of human-mouse hybrid cells, <a href="#32" class="mim-tip-reference" title="Camerino, G., Grzeschik, K. H., Jaye, M., de la Salle, H., Tolstoshev, P., Lecocq, J. P., Heilig, R., Mandel, J. L. <strong>Regional localization on the human X chromosome and polymorphism of the coagulation factor IX gene (hemophilia B locus).</strong> Proc. Nat. Acad. Sci. 81: 498-502, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6320191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6320191</a>] [<a href="https://doi.org/10.1073/pnas.81.2.498" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6320191">Camerino et al. (1984)</a> mapped the F9 locus to Xq26-q27. Furthermore, they identified a TaqI polymorphism with allelic frequencies of about 0.71 and 0.29. By in situ hybridization and by study of rodent-human somatic cell hybrids with various aberrations of the human X, <a href="#25" class="mim-tip-reference" title="Boyd, Y., Buckle, V. J., Munro, E. A., Choo, K. H., Migeon, B. R., Craig, I. W. <strong>Assignment of the haemophilia B (factor IX) locus to the q26-qter region of the X chromosome.</strong> Ann. Hum. Genet. 48: 145-152, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6331274/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6331274</a>] [<a href="https://doi.org/10.1111/j.1469-1809.1984.tb01009.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6331274">Boyd et al. (1984)</a> assigned the factor IX locus to Xq26-qter. <a href="#85" class="mim-tip-reference" title="Jagadeeswaran, P., Lavelle, D. E., Kaul, R., Mohandas, T., Warren, S. T. <strong>Isolation and characterization of human factor IX cDNA: identification of Taq I polymorphism and regional assignment.</strong> Somat. Cell Molec. Genet. 10: 465-473, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6089357/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6089357</a>] [<a href="https://doi.org/10.1007/BF01534851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6089357">Jagadeeswaran et al. (1984)</a> also mapped the F9 gene to Xq26-qter. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6089357+6320191+6331274" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>Hemophilia B</em></strong></p><p>
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Using genomic DNA probes, <a href="#42" class="mim-tip-reference" title="Chen, S.-H., Yoshitake, S., Chance, P. F., Bray, G. L., Thompson, A. R., Scott, C. R., Kurachi, K. <strong>An intragenic deletion of the factor IX gene in a family with hemophilia B.</strong> J. Clin. Invest. 76: 2161-2164, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3001143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3001143</a>] [<a href="https://doi.org/10.1172/JCI112222" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3001143">Chen et al. (1985)</a> identified a partial intragenic deletion in the F9 gene in 7 affected members of a family with severe hemophilia B (<a href="/entry/306900">306900</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3001143" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 affected members of a family with severe factor IX deficiency and no detectable factor IX protein, <a href="#157" class="mim-tip-reference" title="Taylor, S. A. M., Lillicrap, D. P., Blanchette, V., Giles, A. R., Holden, J. J. A., White, B. N. <strong>A complete deletion of the factor IX gene and new TaqI variant in a hemophilia B kindred.</strong> Hum. Genet. 79: 273-276, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2841226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2841226</a>] [<a href="https://doi.org/10.1007/BF00366250" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2841226">Taylor et al. (1988)</a> identified a complete deletion of the F9 gene that extended at least 80 kb 3-prime of the gene. The proband did not have antibodies to factor IX, despite total deletion of the gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2841226" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#114" class="mim-tip-reference" title="Matthews, R. J., Peake, I. R., Bloom, A. L., Anson, D. S. <strong>Carrier detection through the use of abnormal deletion junction fragments in a case of haemophilia B involving complete deletion of the factor IX gene.</strong> J. Med. Genet. 25: 779-780, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2907054/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2907054</a>] [<a href="https://doi.org/10.1136/jmg.25.11.779" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2907054">Matthews et al. (1988)</a> discussed the family originally reported by <a href="#123" class="mim-tip-reference" title="Peake, I. R., Furlong, B. L., Bloom, A. L. <strong>Carrier detection by direct gene analysis in a family with haemophilia B (factor IX deficiency).</strong> Lancet 323: 242-243, 1984. Note: Originally Volume 1.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6142993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6142993</a>] [<a href="https://doi.org/10.1016/s0140-6736(84)90123-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6142993">Peake et al. (1984)</a> as having an X-chromosome deletion of minimum size 114 kb that included the entire F9 gene. By isolation of further 3-prime flanking probes, they located the 3-prime breakpoint of the deletion to a position 145 kb 3-prime to the start of the F9 gene. Abnormal junction fragments detected at the breakpoint were used in the detection of carriers. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6142993+2907054" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 B, <a href="#139" class="mim-tip-reference" title="Siguret, V., Amselem, S., Vidaud, M., Assouline, Z., Kerbiriou-Nabias, D., Pietu, G., Goossens, M., Larrieu, M. J., Bahnak, B., Meyer, D., Lavergne, J. M. <strong>Identification of a CpG mutation in the coagulation factor-IX gene by analysis of amplified DNA sequences.</strong> Brit. J. Haemat. 70: 411-416, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3219291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3219291</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1988.tb02509.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3219291">Siguret et al. (1988)</a> found loss of the TaqI restriction site at the 5-prime end of exon 8 of the F9 gene. Using oligonucleotide probes and PCR-amplified DNA for sequencing of the affected region, the authors identified a C-to-T change in the catalytic domain of the protein, resulting in premature termination. The change resulted from a CpG mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3219291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 PCR followed by sequencing, <a href="#23" class="mim-tip-reference" title="Bottema, C. D. K., Koeberl, D. D., Ketterling, R. P., Lillicrap, D. P., Bridges, P., Sommer, S. S. <strong>The molecular pathology of hemophilia B is a mirror of the pattern of recent germline mutations in humans. (Abstract)</strong> Blood 74: 252A, 1989."None>Bottema et al. (1989)</a> identified mutations in the F9 gene (see, e.g., <a href="#0051">300746.0051</a>) in all 14 hemophilia B patients studied. Analysis for heterozygosity in at-risk female relatives was then done, either by sequencing the appropriate region or by detection of an altered restriction site.</p><p><a href="#77" 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.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1768766/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1768766</a>] [<a href="https://doi.org/10.1097/00001721-199108000-00007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1768766">Green et al. (1991)</a> provided a list of point mutations that cause hemophilia B. <a href="#143" class="mim-tip-reference" title="Sommer, S. S., Bowie, E. J. W., Ketterling, R. P., Bottema, C. D. K. <strong>Missense mutations and the magnitude of functional deficit: the example of factor IX.</strong> Hum. Genet. 89: 295-297, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1601420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1601420</a>] [<a href="https://doi.org/10.1007/BF00220543" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1601420">Sommer et al. (1992)</a> estimated that missense mutations cause only 59% of moderate and severe hemophilia B and that these mutations are almost always (95%) of independent origin (i.e., de novo mutations). In contrast, missense mutations were found in virtually all (97%) families with mild disease and only a minority of these (41%) were of independent origin. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1601420+1768766" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Giannelli, F., Green, P. M., High, K. A., Sommer, S., Poon, M.-C., Ludwig, M., Schwaab, R., Reitsma, P. H., Goossens, M., Yoshioka, A., Brownlee, G. G. <strong>Haemophilia B: database of point mutations and short additions and deletions--fourth edition, 1993.</strong> Nucleic Acids Res. 21: 3075-3087, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8392713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8392713</a>] [<a href="https://doi.org/10.1093/nar/21.13.3075" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8392713">Giannelli et al. (1993)</a> reported on the findings in a database of 806 patients with hemophilia B in whom the defect in factor IX had been identified at the molecular level. A total of 379 independent mutations were described. The list included 234 different amino acid substitutions. There were 13 promoter mutations, 18 mutations in donor splice sites, 15 mutations in acceptor splice sites, and 4 mutations creating cryptic splice sites. In analyses of DNA from 290 families with hemophilia B (203 independent mutations), <a href="#91" class="mim-tip-reference" title="Ketterling, R. P., Vielhaber, E., Sommer, S. S. <strong>The rates of G:C-to-T:A and G:C-to-C:G transversions at CpG dinucleotides in the human factor IX gene.</strong> Am. J. Hum. Genet. 54: 831-835, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8178822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8178822</a>]" pmid="8178822">Ketterling et al. (1994)</a> found 12 deletions more than 20 bp long. Eleven of these were more than 2 kb long and one was 1.1 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8178822+8392713" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#70" class="mim-tip-reference" title="Giannelli, F., Green, P. M., Sommer, S. S., Poon, M.-C., Ludwig, M., Schwaab, R., Reitsma, P. H., Goossens, M., Yoshioka, A., Brownlee, G. G. <strong>Haemophilia B (sixth edition): a database of point mutations and short additions and deletions.</strong> Nucleic Acids Res. 24: 103-118, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8594556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8594556</a>] [<a href="https://doi.org/10.1093/nar/24.1.103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8594556">Giannelli et al. (1996)</a> described the sixth edition of their hemophilia B database of point mutations and short (less than 30 bp) additions and deletions. The 1,380 patient entries were ordered by the nucleotide number of their mutation. References to published mutations were given and the laboratories generating the data were indicated. <a href="#71" class="mim-tip-reference" title="Giannelli, F., Green, P. M., Sommer, S. S., Poon, M.-C., Ludwig, M., Schwaab, R., Reitsma, P. H., Goossens, M., Yoshioka, A., Figueiredo, M. S., Brownlee, G. G. <strong>Haemophilia B: database of point mutations and short additions and deletions, 7th edition.</strong> Nucleic Acids Res. 25: 133-135, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9016521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9016521</a>] [<a href="https://doi.org/10.1093/nar/25.1.133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9016521">Giannelli et al. (1997)</a> described the seventh edition of their database; 1,535 patient entries were ordered by the nucleotide number of their mutation. When known, details were given on factor IX activity, factor IX antigen in the circulation, presence of inhibitor, and origin of mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9016521+8594556" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#106" class="mim-tip-reference" title="Ljung, R., Petrini, P., Tengborn, L., Sjorin, E. <strong>Haemophilia B mutations in Sweden: a population-based study of mutational heterogeneity.</strong> Brit. J. Haemat. 113: 81-86, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11328285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11328285</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2001.02759.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11328285">Ljung et al. (2001)</a> surveyed a series comprising all 77 known families with hemophilia B in Sweden. The disorder was severe in 38, moderate in 10, and mild in 29. A total of 51 different mutations were found. Ten of the mutations, all C-to-T or G-to-A transitions, recurred in 1 to 6 additional families. Using haplotype analysis of 7 polymorphisms in the F9 gene, <a href="#106" class="mim-tip-reference" title="Ljung, R., Petrini, P., Tengborn, L., Sjorin, E. <strong>Haemophilia B mutations in Sweden: a population-based study of mutational heterogeneity.</strong> Brit. J. Haemat. 113: 81-86, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11328285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11328285</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2001.02759.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11328285">Ljung et al. (2001)</a> found that the 77 families carried 65 unique, independent mutations. Of the 48 families with severe or moderate hemophilia, 23 (48%) had a sporadic case compared with 31 families of 78 (40%) in the whole series. Five of those 23 sporadic cases carried de novo mutations; 11 of 23 of the mothers were proven carriers; and in the remaining 7 families, it was not possible to determine carriership. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11328285" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>X-Linked Thrombophilia due to Factor IX Defect</em></strong></p><p>
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In an Italian man with deep venous thrombosis of the femoral-popliteal veins (THPH8; <a href="/entry/300807">300807</a>), <a href="#140" class="mim-tip-reference" title="Simioni, P., Tormene, D., Tognin, G., Gavasso, S., Bulato, C., Iacobelli, N. P., Finn, J. D., Spiezia, L., Radu, C., Arruda, V. R. <strong>X-linked thrombophilia with a mutant factor IX (factor IX Padua).</strong> New Eng. J. Med. 361: 1671-1675, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19846852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19846852</a>] [<a href="https://doi.org/10.1056/NEJMoa0904377" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19846852">Simioni et al. (2009)</a> identified a hemizygous mutation in the F9 gene (R338L; <a href="#0112">300746.0112</a>). Coagulation studies showed that he had normal levels of F9 antigen, but very high levels of F9 activity (776% of control values). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19846852" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Warfarin Sensitivity</em></strong></p><p>
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In a 49-year-old patient who was found to have warfarin sensitivity, <a href="#46" class="mim-tip-reference" title="Chu, K., Wu, S.-M., Stanley, T., Stafford, D. W., High, K. A. <strong>A mutation in the propeptide of factor IX leads to warfarin sensitivity by a novel mechanism.</strong> J. Clin. Invest. 98: 1619-1625, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8833911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8833911</a>] [<a href="https://doi.org/10.1172/JCI118956" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8833911">Chu et al. (1996)</a> identified an A-10T mutation in the propeptide of the factor IX gene (A37T; <a href="#0102">300746.0102</a>). The mutation was found by direct sequence analysis of amplified genomic DNA from all 8 exons and exon-intron junctions of F9. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8833911" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 warfarin sensitivity, <a href="#122" class="mim-tip-reference" title="Oldenburg, J., Quenzel, E.-M., Harbrecht, U., Fregin, A., Kress, W., Muller, C. R., Hertefelder, H.-J., Schwaab, R., Brackmann, H.-H., Hanfland, P. <strong>Missense mutations at ala-10 in the factor IX propeptide: an insignificant variant in normal life but a decisive cause of bleeding during oral anticoagulant therapy.</strong> Brit. J. Haemat. 98: 240-244, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9233593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9233593</a>] [<a href="https://doi.org/10.1046/j.1365-2141.1997.2213036.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9233593">Oldenburg et al. (1997)</a> identified mutations in the F9 gene: A-10T in 1 patient and an A-10V mutation (A37V; <a href="#0103">300746.0103</a>) in the others. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9233593" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Pezeshkpoor, B., Czogalla, K. J., Caspers, M., Berkemeier, A.-C., Liphardt, K., Ghosh, S., Kellner, M., Ulrich, S., Pavlova, A., Oldenburg, J. <strong>Variants in FIX propeptide associated with vitamin K antagonism hypersensitivity: functional analysis and additional data confirming the common founder mutations.</strong> Ann. Hemat. 97: 1061-1069, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29450643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29450643</a>] [<a href="https://doi.org/10.1007/s00277-018-3264-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29450643">Pezeshkpoor et al. (2018)</a> identified the A37T mutation in the F9 gene in 11 patients with X-linked warfarin sensitivity, including 6 patients previously reported by <a href="#121" class="mim-tip-reference" title="Oldenburg, J., Kriz, K., Wuillemin, W. A., Maly, F. E., von Felten, A., Siegemund, A., Keeling, D. M., Baker, P., Chu, K., Konkle, B. A., Lammle, B., Albert, T. <strong>Genetic predisposition to bleeding during oral anticoagulant therapy: evidence for common founder mutations (FIXVal-10 and FIXThr-10) and an independent CpG hotspot mutation (FIXThr-10).</strong> Thromb. Haemost. 85: 454-457, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11307814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11307814</a>]" pmid="11307814">Oldenburg et al. (2001)</a>, and the A37V mutation in 7 patients, including 5 patients previously reported by <a href="#121" class="mim-tip-reference" title="Oldenburg, J., Kriz, K., Wuillemin, W. A., Maly, F. E., von Felten, A., Siegemund, A., Keeling, D. M., Baker, P., Chu, K., Konkle, B. A., Lammle, B., Albert, T. <strong>Genetic predisposition to bleeding during oral anticoagulant therapy: evidence for common founder mutations (FIXVal-10 and FIXThr-10) and an independent CpG hotspot mutation (FIXThr-10).</strong> Thromb. Haemost. 85: 454-457, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11307814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11307814</a>]" pmid="11307814">Oldenburg et al. (2001)</a>. Expression of F9 containing the A37T mutation or the A37V mutation in HEK293T cells resulted in a reduction in the FIX:C ratio and a reduced half maximal inhibitory concentration (IC50) for warfarin compared to HEK293T cells transfected with wildtype F9. This indicated a sensitivity to warfarin conferred by both mutations, with A37V conferring less warfarin sensitivity than A37T. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11307814+29450643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 haplotype analysis in 11 patients with the A37T mutation and 7 patients with the A37V mutation, <a href="#125" class="mim-tip-reference" title="Pezeshkpoor, B., Czogalla, K. J., Caspers, M., Berkemeier, A.-C., Liphardt, K., Ghosh, S., Kellner, M., Ulrich, S., Pavlova, A., Oldenburg, J. <strong>Variants in FIX propeptide associated with vitamin K antagonism hypersensitivity: functional analysis and additional data confirming the common founder mutations.</strong> Ann. Hemat. 97: 1061-1069, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29450643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29450643</a>] [<a href="https://doi.org/10.1007/s00277-018-3264-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29450643">Pezeshkpoor et al. (2018)</a> found that both were founder mutations in the European population. They noted that 2 patients from the US with the A37T mutation (patients J and K in <a href="#121" class="mim-tip-reference" title="Oldenburg, J., Kriz, K., Wuillemin, W. A., Maly, F. E., von Felten, A., Siegemund, A., Keeling, D. M., Baker, P., Chu, K., Konkle, B. A., Lammle, B., Albert, T. <strong>Genetic predisposition to bleeding during oral anticoagulant therapy: evidence for common founder mutations (FIXVal-10 and FIXThr-10) and an independent CpG hotspot mutation (FIXThr-10).</strong> Thromb. Haemost. 85: 454-457, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11307814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11307814</a>]" pmid="11307814">Oldenburg et al., 2001</a>) shared a different haplotype than the 9 European patients with the A37T mutation, indicating an independent origin. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11307814+29450643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Mechanism of Mutation Generation</em></strong></p><p>
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Methylation of CpG dinucleotides constitutes an endogenous mechanism of mutation, which results from insufficient repair of the deamination product to 5-methyl cytosine (<a href="#89" class="mim-tip-reference" title="Ketterling, R. P., Vielhaber, E., Bottema, C. D. K., Schaid, D. J., Cohen, M. P., Sexauer, C. L., Sommer, S. S. <strong>Germ-line origins of mutation in families with hemophilia B: the sex ratio varies with the type of mutation.</strong> Am. J. Hum. Genet. 52: 152-166, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8434583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8434583</a>]" pmid="8434583">Ketterling et al., 1993</a>). Among 22 patients with hemophilia B, <a href="#93" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Buerstedde, J.-M., Sommer, S. S. <strong>Functionally important regions of the factor IX gene have a low rate of polymorphism and a high rate of mutation in the dinucleotide CpG.</strong> Am. J. Hum. Genet. 45: 448-457, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2773937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2773937</a>]" pmid="2773937">Koeberl et al. (1989)</a> found a high rate of mutation at CpG dinucleotides. Transitions of CpG accounted for 31% (5 out of 16) of distinct mutations and for 38% (5 out of 13) of single base changes. The authors used a method of genome amplification with transcript sequencing to perform direct sequencing on 8 regions of the F9 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2773937+8434583" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#47" class="mim-tip-reference" title="Cooper, D. N., Krawczak, M. <strong>The mutational spectrum of single base-pair substitutions causing human genetic disease: patterns and predictions.</strong> Hum. Genet. 85: 55-74, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2192981/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2192981</a>] [<a href="https://doi.org/10.1007/BF00276326" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2192981">Cooper and Krawczak (1990)</a> made an extensive survey of single basepair substitutions that cause various human genetic diseases and found that 32% were CG-to-TG or CG-to-CA transitions. This was a 12-fold increase over the frequency predicted from random expectation. They presented a computer model (MUTPRED) designed to predict the location of mutations within gene coding regions causing human genetic disease. The model predicted successfully the rank order of disease prevalence and/or mutation rates associated with various human autosomal dominant and X-linked recessive conditions. The mutational spectrum predicted for the F9 gene resembled closely that observed for point mutations causing hemophilia B. <a href="#47" class="mim-tip-reference" title="Cooper, D. N., Krawczak, M. <strong>The mutational spectrum of single base-pair substitutions causing human genetic disease: patterns and predictions.</strong> Hum. Genet. 85: 55-74, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2192981/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2192981</a>] [<a href="https://doi.org/10.1007/BF00276326" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2192981">Cooper and Krawczak (1990)</a> quoted from Edmund Spenser's 'The Faerie Queene' (circa 1609): '...mutability in them doth play her cruell cruell sports, to many men's decay.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2192981" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 study the nature of spontaneous mutation, <a href="#94" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Ketterling, R. P., Bridge, P. J., Lillicrap, D. P., Sommer, S. S. <strong>Mutations causing hemophilia B: direct estimate of the underlying rates of spontaneous germ-line transitions, transversions, and deletions in a human gene.</strong> Am. J. Hum. Genet. 47: 202-217, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2198809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2198809</a>]" pmid="2198809">Koeberl et al. (1990)</a> sequenced 8 regions (a total of 2.46 kb) of likely functional significance in the F9 gene in 60 consecutive, unrelated patients with hemophilia B. From the pattern of mutations causing disease and from a knowledge of evolutionarily conserved amino acids, they reconstructed the underlying pattern of mutation and calculated the mutation rates per basepair per generation for transitions (G-A or C-T changes) as 27 x 10(-10), transversions (A-T, A-C, G-T, or G-C changes) as 4.1 x 10(-10), and deletions as 0.9 x 10(-10), for a total mutation rate of 32 x 10(-10). No insertions were observed in this sample. The proportion of transitions at non-CpG dinucleotides was raised 7-fold over that expected if 1 base substitution were as likely as another; at the dinucleotide CpG, transitions were found to be increased 24-fold relative to transitions at other sites. Mutations putatively affecting splicing accounted for at least 13% of mutations, indicating that the division of the gene into 8 exons represents a significant genetic cost to the organism. All the missense mutations occurred at evolutionarily conserved amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2198809" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#21" class="mim-tip-reference" title="Bottema, C. D. K., Ketterling, R. P., Yoon, H.-S., Sommer, S. S. <strong>The pattern of factor IX germ-line mutation in Asians is similar to that of Caucasians.</strong> Am. J. Hum. Genet. 47: 835-841, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2220823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2220823</a>]" pmid="2220823">Bottema et al. (1990)</a> found that in Asians (mostly Koreans), as in Caucasians, transitions dominate among F9 mutations, followed by transversions and microdeletions/insertions. On the basis of their data combined with previous data, the authors concluded that more than two-thirds of the missense mutations that can occur at nonconserved amino acids do not cause hemophilia B. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2220823" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 their series of patients with hemophilia B, <a href="#43" class="mim-tip-reference" title="Chen, S.-H., Zhang, M., Lovrien, E. W., Scott, C. R., Thompson, A. R. <strong>CG dinucleotide transitions in the factor IX gene account for about half of the point mutations in hemophilia B patients: a Seattle series.</strong> Hum. Genet. 87: 177-182, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2066105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2066105</a>] [<a href="https://doi.org/10.1007/BF00204177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2066105">Chen et al. (1991)</a> found that 23 (45%) of 51 substitutions in the F9 gene occurred as C-to-T or G-to-A transitions at 11 sites within CpG dinucleotides. More than 1 family had identical defects for 6 of the CpG mutations. At 4 of these sites, most patients had different haplotypes compatible with distinct mutations. Non-CpG mutations occurred throughout the coding regions with only 1 mutation in more than one family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2066105" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#19" class="mim-tip-reference" title="Bottema, C. D. K., Ketterling, R. P., Ii, S., Yoon, H.-S., Phillips, J. A., III, Sommer, S. S. <strong>Missense mutations and evolutionary conservation of amino acids: evidence that many of the amino acids in factor IX function as 'spacer' elements.</strong> Am. J. Hum. Genet. 49: 820-838, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1680287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1680287</a>]" pmid="1680287">Bottema et al. (1991)</a> identified 95 independent missense mutations in the F9 gene resulting in hemophilia B; 94 of these occurred at amino acids that are evolutionarily conserved in mammalian factor IX sequences. They pointed out that the likelihood of a missense mutation causing hemophilia B depends on whether the residue is also conserved in the factor IX-related proteases: factor VII, factor X (F10; see <a href="/entry/227600">227600</a>), and protein C (PROC; <a href="/entry/612283">612283</a>). They found that most of the possible missense mutations in residues conserved in factor IX in all the related proteases resulted in disease, whereas missense mutations not conserved in the related proteases were 6-fold less likely to cause disease. Missense mutations at nonconserved residues were 33-fold less likely to cause disease. <a href="#19" class="mim-tip-reference" title="Bottema, C. D. K., Ketterling, R. P., Ii, S., Yoon, H.-S., Phillips, J. A., III, Sommer, S. S. <strong>Missense mutations and evolutionary conservation of amino acids: evidence that many of the amino acids in factor IX function as 'spacer' elements.</strong> Am. J. Hum. Genet. 49: 820-838, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1680287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1680287</a>]" pmid="1680287">Bottema et al. (1991)</a> concluded that many of the residues in factor IX are spacers; that is, the main chains are presumably necessary to keep other amino acid interactions in register, but the nature of the side chain is unimportant. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1680287" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#18" class="mim-tip-reference" title="Bottema, C. D. K., Bottema, M. J., Ketterling, R. P., Yoon, H.-S., Janco, R. L., Phillips, J. A., III, Sommer, S. S. <strong>Why does the human factor IX gene have a G+C content of 40%?</strong> Am. J. Hum. Genet. 49: 839-850, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1897528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1897528</a>]" pmid="1897528">Bottema et al. (1991)</a> found that transversions at CpG dinucleotides are elevated an estimated 7.7-fold relative to other transversions. On the other hand, the mutation rates at non-CpG dinucleotides are relatively uniform. They suggested that the high rate of CpG transversions accounts for the fact that the F9 gene has a G+C content of approximately 40%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1897528" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#20" class="mim-tip-reference" title="Bottema, C. D. K., Ketterling, R. P., Vielhaber, E., Yoon, H.-S., Gostout, B., Jacobson, D. P., Shapiro, A., Sommer, S. S. <strong>The pattern of spontaneous germ-line mutation: relative rates of mutation at or near CpG dinucleotides in the factor IX gene.</strong> Hum. Genet. 91: 496-503, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8314564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8314564</a>] [<a href="https://doi.org/10.1007/BF00217779" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8314564">Bottema et al. (1993)</a> gave an updated estimate on mutations at CpG dinucleotides in the F9 gene. Of the independent transitions they had delineated in a consecutive sample of 290 families with hemophilia B, 42% occurred at CpG sites. Overall, CpG mutations represented 36% of the point mutations and 30% of all mutations in their sample. An observed 20-fold enhancement for mutation at CpG sites with frequent mutations reflected, they suggested, the situation at fully or mostly methylated sites. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8314564" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Based particularly on his extensive experience with mutation analysis in hemophilia B, <a href="#144" class="mim-tip-reference" title="Sommer, S. S. <strong>Does cancer kill the individual and save the species? (Letter)</strong> Hum. Mutat. 3: 166-169, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8199598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8199598</a>] [<a href="https://doi.org/10.1002/humu.1380030214" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8199598">Sommer (1994)</a> proposed an ingenious hypothesis concerning the role of cancer in mediating evolutionary selection for a constant rate of germline mutation. The hypothesis was based on data suggesting that most germline mutations are due to endogenous processes such as methylation of DNA at CpG dinucleotides. Furthermore, despite differences in environment, diet, lifestyle, and occupational exposure, the pattern of factor IX mutations is remarkably similar in populations all over the world. Also despite the many differences in the environment of modern day humans, the biases in the dinucleotide mutation rates during the past 150 years are compatible with the ancient pattern that fashioned the G+C content of 40%. Assuming that somatic mutation leading to early-onset cancer occurs at rates similar to the germline mutation rate, then these cancers that interfere with reproduction might cap the germline mutation rate. Some have pointed out that cancer is a sensitive mediator of negative selection because the multiple mutations required for carcinogenesis can amplify the effects of small increases in the mutation rate. A certain rate of mutation is required to generate sufficient variation for adaptation during evolutionary time. Sexual reproduction and recombination serves to enhance variation, but ultimately new germline mutation is required to replenish variant alleles lost secondary to negative selection, genetic drift, and population bottlenecks. Unfortunately, the requisite mutation rate carries a terrible price, since for each advantageous mutation, there are many disadvantageous ones. Consequently, the optimal mutation rate should be at a level just sufficient to maintain the variation needed for adaptation. Mechanisms for negative selection are needed to keep the mutation rate in check. Cancer may serve that role. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8199598" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 727 independent mutations (0.28%) of the F9 gene in patients with hemophilia B, <a href="#102" class="mim-tip-reference" title="Li, X., Scaringe, W. A., Hill, K. A., Roberts, S., Mengos, A., Careri, D., Pinto, M. T., Kasper, C. K., Sommer, S. S. <strong>Frequency of recent retrotransposition events in the human factor IX gene.</strong> Hum. Mutat. 17: 511-519, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11385709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11385709</a>] [<a href="https://doi.org/10.1002/humu.1134" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11385709">Li et al. (2001)</a> observed only 2 germline retrotransposition mutations: a 279-bp insertion in exon 8 originating from an Alu family of short interspersed elements not previously known to be active, and a 463-bp insertion in exon e of a LINE-1 element originating in a maternal grandmother. The authors stated that if the rates of recent germline mutation in F9 are typical of the genome, a retrotransposition event is estimated to occur somewhere in the genome of about 1 in every 17 children born. Analysis of other estimates for retrotransposition frequency and overall mutation rates suggested that the actual rate of retrotransposition is likely to be in the range of 1 in every 2.4 to 1 in every 28 live births. <a href="#87" class="mim-tip-reference" title="Kazazian, H. H., Jr. <strong>An estimated frequency of endogenous insertional mutations in humans.</strong> Nature Genet. 22: 130 only, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369250/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369250</a>] [<a href="https://doi.org/10.1038/9638" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10369250">Kazazian (1999)</a> analyzed the frequency of retrotransposition events involving 860 genes. These included retrotranspositions identified in X-linked and severe autosomal dominant disorders, likely to have occurred within the last 150 years, and autosomal recessive disorders in which the mutations may have occurred 10,000 or more years ago. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11385709+10369250" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="#82" class="mim-tip-reference" title="Hirosawa, S., Fahner, J. B., Salier, J.-P., Wu, C.-T., Lovrien, E. W., Kurachi, K. <strong>Structural and functional basis of the developmental regulation of human coagulation factor IX gene: factor IX Leyden.</strong> Proc. Nat. Acad. Sci. 87: 4421-4425, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2352926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2352926</a>] [<a href="https://doi.org/10.1073/pnas.87.12.4421" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2352926">Hirosawa et al. (1990)</a> noted that all 5 families with hemophilia B Leyden, in which a severe bleeding disorder in childhood becomes mild after puberty, had mutations in an approximately 40-kb region in the 5-prime untranslated region of F9, which the authors referred to as the Leyden-specific region (LSR). Base changes at nucleotide -20 (<a href="#0001">300746.0001</a>) as well as at nucleotide -6 (<a href="#0002">300746.0002</a>) and deletions of the 3-prime half of the LS region reduced expression of the factor IX gene to about 15-31% that of normal controls, as assessed in a cultured cell (HepG2) expression system. Androgen significantly increased the transcriptional activities of both mutant and normal factor IX genes in a concentration-dependent manner. The findings suggested that a mutations in this region could lead to a switch from constitutive to steroid hormone-dependent gene expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2352926" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#100" class="mim-tip-reference" title="Kurachi, S., Huo, J. S., Ameri, A., Zhang, K., Yoshizawa, A. C., Kurachi, K. <strong>An age-related homeostasis mechanism is essential for spontaneous amelioration of hemophilia B Leyden.</strong> Proc. Nat. Acad. Sci. 106: 7921-7926, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19416882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19416882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19416882[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.0902191106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19416882">Kurachi et al. (2009)</a> stated that the LSR has been narrowed to an approximately 50-bp region between nucleotides -34 and +19. <a href="#49" class="mim-tip-reference" title="Crossley, M., Brownlee, G. G. <strong>Disruption of a C/EBP binding site in the factor IX promoter is associated with haemophilia B.</strong> Nature 345: 444-446, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2342576/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2342576</a>] [<a href="https://doi.org/10.1038/345444a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2342576">Crossley and Brownlee (1990)</a> identified a binding site for the CCAAT/enhancer binding protein (C/EBP, CEBPA; <a href="/entry/116897">116897</a>) extending from +1 to +18 in the F9 gene, which is capable of transactivating a factor IX promoter. Hepatocyte nuclear factor-4 (HNF4; <a href="/entry/600281">600281</a>), a member of the steroid hormone receptor superfamily of transcription factors, also binds to nucleotides -26 to -20 of the promoter region in the F9 gene (<a href="#130" class="mim-tip-reference" title="Reijnen, M. J., Sladek, F. M., Bertina, R. M., Reitsma, P. H. <strong>Disruption of a binding site for hepatocyte nuclear factor 4 results in hemophilia B Leyden.</strong> Proc. Nat. Acad. Sci. 89: 6300-6303, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1631121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1631121</a>] [<a href="https://doi.org/10.1073/pnas.89.14.6300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1631121">Reijnen et al., 1992</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1631121+19416882+2342576" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="#97" class="mim-tip-reference" title="Kundu, R. K., Sangiorgi, F., Wu, L.-Y., Kurachi, K., Anderson, W. F., Maxson, R., Gordon, E. M. <strong>Targeted inactivation of the coagulation factor IX gene causes hemophilia B in mice.</strong> Blood 92: 168-174, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9639513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9639513</a>]" pmid="9639513">Kundu et al. (1998)</a> generated a transgenic mouse model of hemophilia B by targeted disruption of the murine F9 gene. The tail bleeding time of hemizygous male mice was markedly prolonged compared with those of normal and carrier female littermates. Seven of 19 affected male mice died of exsanguination after tail snipping, and 2 affected mice died of umbilical cord bleeding. Ten affected mice survived to 4 months of age. Aside from the factor IX defect, carrier female and hemizygous male mice had no liver pathology by histologic examination, were fertile, and transmitted the mutation in the expected mendelian frequency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9639513" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#80" class="mim-tip-reference" title="Gu, W., Brooks, M., Catalfamo, J., Ray, J., Ray, K. <strong>Two distinct mutations cause severe hemophilia B in two unrelated canine pedigrees.</strong> Thromb. Haemost. 82: 1270-1275, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10544912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10544912</a>]" pmid="10544912">Gu et al. (1999)</a> found factor IX deficiency in 2 distinct dog breeds. In 1 breed, the disorder was associated with a large deletion mutation, spanning the entire 5-prime region of the F9 gene extending to exon 6. In the second breed, an insertion of approximately 5 kb disrupted exon 8. The insertion was associated with alternative splicing between a donor site 5-prime and acceptor site 3-prime to the normal exon 8 splice junction, with introduction of a new stop codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10544912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Brooks, M. B., Gu, W., Barnas, J. L., Ray, J., Ray, K. <strong>A line 1 insertion in the factor IX gene segregates with mild hemophilia B in dogs.</strong> Mammalian Genome 14: 788-795, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14722728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14722728</a>] [<a href="https://doi.org/10.1007/s00335-003-2290-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14722728">Brooks et al. (2003)</a> found that mild hemophilia B in a large pedigree of German wirehaired pointers was caused by a line-1 insertion in the factor IX gene. The insertion could be traced through at least 5 generations and segregated with the hemophilia B phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14722728" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Blood coagulation capacity increases with age in healthy individuals. Through extensive longitudinal analyses of human factor IX gene expression in transgenic mice, <a href="#99" class="mim-tip-reference" title="Kurachi, S., Deyashiki, Y., Takeshita, J., Kurachi, K. <strong>Genetic mechanisms of age regulation of human blood coagulation factor IX.</strong> Science 285: 739-743, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10426997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10426997</a>] [<a href="https://doi.org/10.1126/science.285.5428.739" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10426997">Kurachi et al. (1999)</a> identified 2 essential age regulatory elements that they termed AE5-prime and AE3-prime. These elements are required and together are sufficient for normal age regulation of factor IX expression. AE5-prime, located between nucleotides -770 through -802, is a PEA3-related element present in the 5-prime upstream region of the gene encoding factor IX and is responsible for age-stable expression of the gene. AE3-prime, located in the middle of the 3-prime untranslated region, is responsible for age-associated elevation in mRNA levels. In a concerted manner, AE5-prime and AE3-prime recapitulate natural patterns of the advancing age-associated increase in factor IX gene expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10426997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 transgenic mice with hemophilia B Leyden (-20T-A; <a href="#0001">300746.0001</a>), which usually show amelioration of the disorder after puberty, <a href="#100" class="mim-tip-reference" title="Kurachi, S., Huo, J. S., Ameri, A., Zhang, K., Yoshizawa, A. C., Kurachi, K. <strong>An age-related homeostasis mechanism is essential for spontaneous amelioration of hemophilia B Leyden.</strong> Proc. Nat. Acad. Sci. 106: 7921-7926, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19416882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19416882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19416882[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.0902191106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19416882">Kurachi et al. (2009)</a> found that expression of different F9 minigenes with or without the age-related stability element (ASE) in the 5-prime untranslated region resulted in different disease course. Mice with no ASE failed to show the Leyden phenotype, showing only transient F9 expression at puberty, whereas mice with ASE showed normal pubertal F9 recovery. These changes were not sex-dependent, indicating that testosterone and androgen are not responsible. Further studies showed that the transcription factor Ets1 (<a href="/entry/164720">164720</a>) was the specific ASE-binding protein responsible for its activation and F9 gene expression. In addition, F9 expression was abolished by hypophysectomy, but restored with growth hormone (GH; <a href="/entry/139250">139250</a>) administration in both males and females. These results provided a molecular mechanism for the puberty-related Leyden phenotype. <a href="#100" class="mim-tip-reference" title="Kurachi, S., Huo, J. S., Ameri, A., Zhang, K., Yoshizawa, A. C., Kurachi, K. <strong>An age-related homeostasis mechanism is essential for spontaneous amelioration of hemophilia B Leyden.</strong> Proc. Nat. Acad. Sci. 106: 7921-7926, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19416882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19416882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19416882[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.0902191106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19416882">Kurachi et al. (2009)</a> also generated transgenic mice expressing the Brandenberg F9 mutation (-26G-C; <a href="#0097">300746.0097</a>), which showed a severe phenotype without amelioration after puberty. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19416882" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs1178811105 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1178811105;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/rs1178811105?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=rs1178811105" 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=rs1178811105" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p><a href="#163" class="mim-tip-reference" title="Veltkamp, J. J., Meilof, J., Remmelts, H. G., Van der Vlerk, D., Loeliger, E. A. <strong>Another genetic variant of haemophilia B: haemophilia B Leyden.</strong> Scand. J. Haemat. 7: 82-90, 1970.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5450691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5450691</a>] [<a href="https://doi.org/10.1111/j.1600-0609.1970.tb01873.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5450691">Veltkamp et al. (1970)</a> described a variant of hemophilia B, termed hemophilia B Leyden (see <a href="/entry/306900">306900</a>), in a Dutch family. The disorder was characterized by the disappearance of the bleeding diathesis as the patient aged. In affected individuals, plasma factor IX levels were less than 1% of normal before puberty, but after puberty factor IX activity and antigen levels rose steadily in a 1:1 ratio to a maximum of 50 to 60%. <a href="#28" class="mim-tip-reference" title="Briet, E., Bertina, R. M., van Tilburg, N. H., Veltkamp, J. J. <strong>Hemophilia B Leyden: a sex-linked hereditary disorder that improves after puberty.</strong> New Eng. J. Med. 306: 788-790, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7062952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7062952</a>] [<a href="https://doi.org/10.1056/NEJM198204013061306" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7062952">Briet et al. (1982)</a> described a similar variant of hemophilia B that took a severe form early in life but remitted after puberty, with an increase in factor IX levels from below 1% of normal to about 50% of normal by age 80 years. Three pedigrees with 27 affected males with this disorder could be traced to a small village in the east of the Netherlands. In affected members of 2 Dutch pedigrees with hemophilia B Leyden, <a href="#131" class="mim-tip-reference" title="Reitsma, P. H., Bertina, R. M., Ploos van Amstel, J. K., Riemens, A., Briet, E. <strong>The putative factor IX gene promoter in hemophilia B Leyden.</strong> Blood 72: 1074, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3416069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3416069</a>]" pmid="3416069">Reitsma et al. (1988)</a> found that patients with hemophilia B Leyden had a T-to-A transversion in the promoter region of the F9 gene at position -20. The findings suggested that a point mutation in this region could lead to a switch from constitutive to steroid hormone-dependent gene expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5450691+7062952+3416069" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#130" class="mim-tip-reference" title="Reijnen, M. J., Sladek, F. M., Bertina, R. M., Reitsma, P. H. <strong>Disruption of a binding site for hepatocyte nuclear factor 4 results in hemophilia B Leyden.</strong> Proc. Nat. Acad. Sci. 89: 6300-6303, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1631121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1631121</a>] [<a href="https://doi.org/10.1073/pnas.89.14.6300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1631121">Reijnen et al. (1992)</a> demonstrated that the -20 promoter mutation disrupts the binding of hepatocyte nuclear factor-4 (HNF4; <a href="/entry/600281">600281</a>), a member of the steroid hormone receptor superfamily of transcription factors. Studies also demonstrated that the G-to-C mutation at -26 (<a href="#0097">300746.0097</a>) also disrupts the binding of HNF4. Whereas HNF4 transactivated the wildtype promoter sequence in liver and nonliver (e.g., HeLa) cell types, it transactivated the -20 mutated promoter to only a limited extent and the -26 mutated promoter not at all. The data suggested that HNF4 is a major factor controlling factor IX expression in the normal individual. Furthermore, the severity of the hemophilia phenotype appeared to be related directly to the degree of disruption of HNF4 binding and transactivation; the -26 G-to-C mutation was accompanied by a bleeding tendency did not ameliorate after puberty. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1631121" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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">rs1166164399 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1166164399;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=rs1166164399" 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=rs1166164399" 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=RCV000795083 OR RCV001815011 OR RCV004586929" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000795083, RCV001815011, RCV004586929" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000795083...</a>
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<p><a href="#61" class="mim-tip-reference" title="Fahner, J. B., Salier, J. P., Landa, L., Hirosawa, S., Lovrien, E. W., Kurachi, K. <strong>Defective promoter structure in a human factor IX-Leyden. (Abstract)</strong> Blood 72: 295A, 1988."None>Fahner et al. (1988)</a> found a G-to-A change at nucleotide -6 as the cause of hemophilia B Leyden (see <a href="/entry/306900">306900</a>), in which a severe bleeding disorder in childhood becomes mild after puberty.</p><p><a href="#51" class="mim-tip-reference" title="Crossley, M., Winship, P. R., Austen, D. E. G., Rizza, C. R., Brownlee, G. G. <strong>A less severe form of haemophilia B Leyden.</strong> Nucleic Acids Res. 18: 4633, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2388855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2388855</a>] [<a href="https://doi.org/10.1093/nar/18.15.4633" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2388855">Crossley et al. (1990)</a> also identified a G-to-A change at position -6 as the cause of hemophilia B Leyden. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2388855" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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=RCV000795083 OR RCV001815011 OR RCV004586929" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000795083, RCV001815011, RCV004586929" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000795083...</a>
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<p><a href="#5" class="mim-tip-reference" title="Attree, O., Vidaud, D., Vidaud, M., Amselem, S., Lavergne, J.-M., Goossens, M. <strong>Mutations in the catalytic domain of human coagulation factor IX: rapid characterization by direct genomic sequencing of DNA fragments displaying an altered melting behavior.</strong> Genomics 4: 266-272, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2714791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2714791</a>] [<a href="https://doi.org/10.1016/0888-7543(89)90330-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2714791">Attree et al. (1989)</a> found a G-to-C change at nucleotide -6. <a href="#164" class="mim-tip-reference" title="Vidaud, D., Tartary, M., Costa, J.-M., Bahnak, B. R., Gispert-Sanchez, S., Fressinaud, E., Gazengel, C., Meyer, D., Goossens, M., Lavergne, J.-M., Vidaud, M. <strong>Nucleotide substitutions at the -6 position in the promoter region of the factor IX gene result in different severity of hemophilia B Leyden: consequences for genetic counseling.</strong> Hum. Genet. 91: 241-244, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8478007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8478007</a>] [<a href="https://doi.org/10.1007/BF00218264" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8478007">Vidaud et al. (1993)</a> cited evidence indicating that the G-C transversion at position -6 produces much milder hemophilia B Leyden (see <a href="/entry/306900">306900</a>) than does the G-A transition at the same position (<a href="#0002">300746.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2714791+8478007" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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">rs2148352878 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2148352878;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=rs2148352878" 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=rs2148352878" 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=RCV000011307" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011307" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011307</a>
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<p><a href="#132" class="mim-tip-reference" title="Reitsma, P. H., Mandalaki, T., Kasper, C. K., Bertina, R. M., Briet, E. <strong>Two novel point mutations correlate with an altered developmental expression of blood coagulation factor IX (hemophilia B Leyden phenotype).</strong> Blood 73: 743-746, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2917196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2917196</a>]" pmid="2917196">Reitsma et al. (1989)</a> studied the F9 gene in a Greek patient and an American patient of Armenian descent with hemophilia B Leyden (see <a href="/entry/306900">306900</a>). In one they found deletion of A at position +13 of the factor IX gene and in the other an A-to-G mutation at the same position (<a href="#0090">300746.0090</a>), 32 bp downstream of the point mutation in the Dutch kindred (<a href="#131" class="mim-tip-reference" title="Reitsma, P. H., Bertina, R. M., Ploos van Amstel, J. K., Riemens, A., Briet, E. <strong>The putative factor IX gene promoter in hemophilia B Leyden.</strong> Blood 72: 1074, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3416069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3416069</a>]" pmid="3416069">Reitsma et al., 1988</a>). See also <a href="#52" class="mim-tip-reference" title="Crossley, P. M., Winship, P. R., Black, A., Rizza, C. R., Brownlee, G. G. <strong>Unusual case of haemophilia B. (Letter)</strong> Lancet 333: 960 only, 1989. Note: Originally Volume 1.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2565449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2565449</a>] [<a href="https://doi.org/10.1016/s0140-6736(89)92540-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2565449">Crossley et al. (1989)</a>. <a href="#49" class="mim-tip-reference" title="Crossley, M., Brownlee, G. G. <strong>Disruption of a C/EBP binding site in the factor IX promoter is associated with haemophilia B.</strong> Nature 345: 444-446, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2342576/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2342576</a>] [<a href="https://doi.org/10.1038/345444a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2342576">Crossley and Brownlee (1990)</a> identified a binding site for the CCAAT/enhancer binding protein (C/EBP) extending from +1 to +18. They showed that the A-to-G mutation at +13 prevents the binding of C/EBP to this site. Furthermore, they showed that C/EBP is capable of transactivating a cotransfected normal factor IX promoter but not the mutant promoter. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3416069+2565449+2917196+2342576" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs150190385 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs150190385;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/rs150190385?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=rs150190385" 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=rs150190385" 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=RCV000291239 OR RCV001080823 OR RCV002488831 OR RCV003389717 OR RCV003970084 OR RCV004992192" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000291239, RCV001080823, RCV002488831, RCV003389717, RCV003970084, RCV004992192" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000291239...</a>
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<p><a href="#93" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Buerstedde, J.-M., Sommer, S. S. <strong>Functionally important regions of the factor IX gene have a low rate of polymorphism and a high rate of mutation in the dinucleotide CpG.</strong> Am. J. Hum. Genet. 45: 448-457, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2773937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2773937</a>]" pmid="2773937">Koeberl et al. (1989)</a> described a normal variant, isoleucine or phenylalanine, at position -40 in exon 1 of the F9 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2773937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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><div class="mim-changed mim-change">.0006 F9 POLYMORPHISM</div></strong>
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F9, IVS1, 192A-G
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV004991969" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV004991969" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV004991969</a>
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<p><a href="#152" class="mim-tip-reference" title="Tanimoto, M., Kojima, T., Kamiya, T., Takamatsu, J., Ogata, K., Obata, Y., Inagaki, M., Iizuka, A., Nagao, T., Kurachi, K., Saito, H. <strong>DNA analysis of seven patients with hemophilia B who have anti-factor IX antibodies: relationship to clinical manifestations and evidence that the abnormal gene was inherited.</strong> J. Lab. Clin. Med. 112: 307-313, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3411192/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3411192</a>]" pmid="3411192">Tanimoto et al. (1988)</a> found a normal polymorphism, A to G, at nucleotide 192 in IVS1 of the F9 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3411192" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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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<strong>.0007 HEMOPHILIA B</strong>
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F9, ARG-4TRP
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1603264205 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1603264205;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=rs1603264205" 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=rs1603264205" 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=RCV001001419 OR RCV001815019 OR RCV001860507" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001001419, RCV001815019, RCV001860507" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001001419...</a>
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<span class="mim-text-font">
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<p>In a review of known factor IX mutations from all hemophilia B (<a href="/entry/306900">306900</a>) patients registered at the Malmo hemophilia center in Sweden and from the entire UK hemophilia population, <a href="#78" class="mim-tip-reference" title="Green, P. M., Montandon, A. J., Ljung, R., Nilsson, I. M., Giannelli, F. <strong>Haplotype analysis of identical factor IX mutants using PCR.</strong> Thromb. Haemost. 67: 66-69, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1615486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1615486</a>]" pmid="1615486">Green et al. (1992)</a> noted that 4 of 7 arg-4trp (R-4W) mutations, resulting from a 6364C-T transition, occurred on different haplotypes, indicating that they were independent mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1615486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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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<h4>
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<span class="mim-font">
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<strong>.0008 HEMOPHILIA B</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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F9, ARG-4GLN
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1275708479 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1275708479;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=rs1275708479" 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=rs1275708479" 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=RCV001000159 OR RCV001815018 OR RCV001869416 OR RCV002462253" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001000159, RCV001815018, RCV001869416, RCV002462253" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001000159...</a>
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</span>
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<p>This variant has been called factor IX San Dimas and factor IX Kawachinagano.</p><p>In a case (designated Ox3) of severe hemophilia B (<a href="/entry/306900">306900</a>) of the CRM-positive type, <a href="#7" class="mim-tip-reference" title="Bentley, A. K., Rees, D. J. G., Rizza, C., Brownlee, G. G. <strong>Defective propeptide processing of blood clotting factor IX caused by mutation of arginine to glutamine at position -4.</strong> Cell 45: 343-348, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3009023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3009023</a>] [<a href="https://doi.org/10.1016/0092-8674(86)90319-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3009023">Bentley et al. (1986)</a> of Oxford University found mutation of arginine to glutamine at position -4, leading to defective cleavage of the N-terminal propeptide. The type of mutation in this mutant factor IX is similar to that in the procollagen molecule (either the alpha-1 or alpha-2 chain of type I collagen) in cases of type VII Ehlers-Danlos syndrome. Two proteolytic cleavages normally occur to remove the prepeptide and the propeptide regions. The mutant F9 had 18 additional amino acids on the N-terminal portion. Normally the signal peptidase cleaves the peptide bond between residues -18 and -19. Further cleavage to mature F9 depends on the arginine residue at -4. Arginine at -4 shows evolutionary conservation in factor X, prothrombin, C3, C4, C5, and tissue type plasminogen activator--all proteins that, like F9, are processed by site-specific trypsin-like enzymes. In addition to the CRM-positive and CRM-negative forms, there is a CRM-reduced class. <a href="#150" class="mim-tip-reference" title="Sugimoto, M., Miyata, T., Kawabata, S., Yoshioka, A., Fukui, H., Iwanaga, S. <strong>Factor IX Kawachinagano: impaired function of the Gla-domain caused by attached propeptide region due to substitution of arginine by glutamine at position -4.</strong> Brit. J. Haemat. 72: 216-221, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2757966/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2757966</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1989.tb07685.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2757966">Sugimoto et al. (1989)</a> demonstrated by amino acid sequence that the mutant factor IX retained the propeptide region of 18 amino acids due to a substitution of arginine at position -4 by glutamine. They assumed that this attached propeptide region of the molecule directly interferes with the adjacent NH(2)-terminus and prevents the metal-induced conformational changes that are essential for biologic activity of normal factor IX. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3009023+2757966" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#174" class="mim-tip-reference" title="Ware, J., Diuguid, D. L., Liebman, H. A., Rabiet, M.-J., Kasper, C. K., Furie, B. C., Furie, B., Stafford, D. W. <strong>Factor IX San Dimas: substitution of glutamine for arg(-4) in the propeptide leads to incomplete gamma-carboxylation and altered phospholipid binding properties.</strong> J. Biol. Chem. 264: 11401-11406, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2738071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2738071</a>]" pmid="2738071">Ware et al. (1989)</a> studied the intragenic defect in factor IX San Dimas, which was derived from a patient with moderately severe hemophilia B (<a href="/entry/306900">306900</a>) who had 98% factor IX antigen but very low factor IX clotting activity. They found that a G-to-A transition in exon 2 of the F9 gene resulted in the substitution of a glutamine for an arginine codon -4 in the propeptide of factor IX. The variant protein circulated in the plasma as profactor IX with a mutant 18-amino acid propeptide still attached. Factor IX San Dimas shows similarities to factor IX Cambridge, which has a substitution of serine for arginine at -1 (<a href="#0009">300746.0009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2738071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Factor IX Kawachinagano is a mutant factor IX protein initially recognized in a patient with severe hemophilia B who had 46% of normal factor IX antigen but no detectable clotting activity. This mutant factor IX is not activated by factor XIa in the presence of calcium ions. <a href="#150" class="mim-tip-reference" title="Sugimoto, M., Miyata, T., Kawabata, S., Yoshioka, A., Fukui, H., Iwanaga, S. <strong>Factor IX Kawachinagano: impaired function of the Gla-domain caused by attached propeptide region due to substitution of arginine by glutamine at position -4.</strong> Brit. J. Haemat. 72: 216-221, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2757966/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2757966</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1989.tb07685.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2757966">Sugimoto et al. (1989)</a> determined that factor IX Kawachinagano results from an arg-to-gln substitution at the -4 position of the F9 gene. The substitution resulted in impaired function of the Gla-domain caused by an attached propeptide region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2757966" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 B</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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F9, ARG-1SER
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</div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011311" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011311" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011311</a>
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</span>
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<p><a href="#58" class="mim-tip-reference" title="Diuguid, D. L., Rabiet, M. J., Furie, B. C., Liebman, H. A., Furie, B. <strong>Molecular basis of hemophilia B: a defective enzyme due to an unprocessed propeptide is caused by a point mutation in the factor IX precursor.</strong> Proc. Nat. Acad. Sci. 83: 5803-5807, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3461460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3461460</a>] [<a href="https://doi.org/10.1073/pnas.83.16.5803" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3461460">Diuguid et al. (1986)</a> found that mutant factor IX Cambridge, isolated from a patient with severe hemophilia B (<a href="/entry/306900">306900</a>), has an 18-residue propeptide attached to its NH2-end. A point mutation at residue -1, from arginine to serine, precluded cleavage of the propeptide by the processing protease and interfered also with gamma-carboxylation of the mutant factor IX. The last effect indicates the importance of the leader sequence in substrate recognition by the vitamin K-dependent carboxylase. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3461460" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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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<span class="mim-font">
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<strong>.0010 HEMOPHILIA B</strong>
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F9, GLU7ASP
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011312" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011312" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011312</a>
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<p>See <a href="#179" class="mim-tip-reference" title="Winship, P. R. <strong>Characterisation of the molecular defect in haemophilia B patients using the polymerase chain reaction procedure. (Abstract)</strong> Thromb. Haemost. 62: 465, 1989."None>Winship (1989)</a>.</p>
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<a id="0011" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0011 HEMOPHILIA B</strong>
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F9, GLN11TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852223 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852223;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=rs137852223" 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=rs137852223" 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=RCV000011313" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011313" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011313</a>
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<p>See <a href="#179" class="mim-tip-reference" title="Winship, P. R. <strong>Characterisation of the molecular defect in haemophilia B patients using the polymerase chain reaction procedure. (Abstract)</strong> Thromb. Haemost. 62: 465, 1989."None>Winship (1989)</a>; the patient studied had a severe form of hemophilia B (<a href="/entry/306900">306900</a>).</p>
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<a id="0012" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0012 HEMOPHILIA B</strong>
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F9, CYS18ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906474 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906474;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=rs387906474" 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=rs387906474" 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=RCV000011314" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011314" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011314</a>
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<p>Information was provided by <a href="#14" class="mim-tip-reference" title="Bertina, R. M. <strong>Personal Communication.</strong> Leiden, The Netherlands 1989."None>Bertina (1989)</a>; the patient studied had a severe form of hemophilia B (<a href="/entry/306900">306900</a>).</p>
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<a id="0013" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0013 HEMOPHILIA B</strong>
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</h4>
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<div style="float: left;">
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F9, GLU27LYS
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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">rs387906475 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906475;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=rs387906475" 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=rs387906475" 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=RCV000011316 OR RCV004689413" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011316, RCV004689413" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011316...</a>
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</span>
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<span class="mim-text-font">
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<p>This variant has been designated factor IX Seattle-3.</p><p><a href="#39" class="mim-tip-reference" title="Chen, S.-H., Scott, C. R., Schoof, J., Lovrien, E. W., Kurachi, K. <strong>Factor IX(Portland): a nonsense mutation (CGA to TGA) resulting in hemophilia B.</strong> Am. J. Hum. Genet. 44: 567-569, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2929599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2929599</a>]" pmid="2929599">Chen et al. (1989)</a> studied 5 patients with severe hemophilia B (<a href="/entry/306900">306900</a>) and detectable factor IX antigen that showed altered reactivity to a specific polyclonal antibody fraction or monoclonal anti-factor IX antibody. By the PCR technique, they identified a single base transition in each of the 5 families. Three different mutations were identified: factor IX Seattle-3 showed a G-to-A transition in exon 2, changing the codon for glu27 to lys; factor IX Durham showed a G-to-A transition in exon 4, changing the codon for gly60 to ser; and factor IX Seattle-4 showed a G-to-A transition in exon 8, changing arg248 to gln in exon 8. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2929599" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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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</div>
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<a id="0014" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0014 HEMOPHILIA B</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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F9, GLU27VAL
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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">rs137852226 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852226;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=rs137852226" 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=rs137852226" 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=RCV000011317" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011317" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011317</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>This variant has been designated factor IX Chongqing.</p><p><a href="#172" class="mim-tip-reference" title="Wang, N. S., Zhang, M., Thompson, A. R., Chen, S.-H. <strong>Factor IX(Chongqing): a new mutation in the calcium-binding domain of factor IX resulting in severe hemophilia B.</strong> Thromb. Haemost. 63: 24-26, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2339358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2339358</a>]" pmid="2339358">Wang et al. (1990)</a> studied a Chinese patient with sporadic hemophilia B (<a href="/entry/306900">306900</a>) of severe form. A defect in the factor IX Gla domain was suspected because of low antigen on an assay using a calcium-dependent antibody fraction. Since the Gla domain is coded mainly by exon 2, <a href="#172" class="mim-tip-reference" title="Wang, N. S., Zhang, M., Thompson, A. R., Chen, S.-H. <strong>Factor IX(Chongqing): a new mutation in the calcium-binding domain of factor IX resulting in severe hemophilia B.</strong> Thromb. Haemost. 63: 24-26, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2339358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2339358</a>]" pmid="2339358">Wang et al. (1990)</a> amplified and sequenced the exon and found an A-to-T substitution at nucleotide 6455. The transversion changed glutamic acid-27 to valine. In leukocyte DNA from the patient's mother, the nucleotide sequence of exon 2 was entirely normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2339358" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="0015" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0015 HEMOPHILIA B</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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F9, ARG29TER
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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">rs137852227 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852227;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=rs137852227" 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=rs137852227" 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=RCV000011318 OR RCV000696946 OR RCV001810844" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011318, RCV000696946, RCV001810844" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011318...</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>See <a href="#75" class="mim-tip-reference" title="Green, P. M., Bentley, D. R., Mibashan, R. S., Nilsson, I. M., Giannelli, F. <strong>Molecular pathology of haemophilia B.</strong> EMBO J. 8: 1067-1072, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2743975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2743975</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1989.tb03474.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2743975">Green et al. (1989)</a>. This mutation, which is due to a transition at a CpG dinucleotide, was found by <a href="#94" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Ketterling, R. P., Bridge, P. J., Lillicrap, D. P., Sommer, S. S. <strong>Mutations causing hemophilia B: direct estimate of the underlying rates of spontaneous germ-line transitions, transversions, and deletions in a human gene.</strong> Am. J. Hum. Genet. 47: 202-217, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2198809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2198809</a>]" pmid="2198809">Koeberl et al. (1990)</a> in 2 cases of severe hemophilia B (<a href="/entry/306900">306900</a>). <a href="#94" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Ketterling, R. P., Bridge, P. J., Lillicrap, D. P., Sommer, S. S. <strong>Mutations causing hemophilia B: direct estimate of the underlying rates of spontaneous germ-line transitions, transversions, and deletions in a human gene.</strong> Am. J. Hum. Genet. 47: 202-217, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2198809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2198809</a>]" pmid="2198809">Koeberl et al. (1990)</a> estimated that approximately 1 in 4 individuals with hemophilia B can be expected to have a mutation at arginine and concluded that nonsense mutations at 1 of the 6 arginine residues are common causes of severe hemophilia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2198809+2743975" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="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 B</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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F9, ARG29GLN
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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> rs137852228 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852228;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/rs137852228?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=rs137852228" 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=rs137852228" 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=RCV000011319 OR RCV000757260 OR RCV000852079 OR RCV001851790 OR RCV002490353" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011319, RCV000757260, RCV000852079, RCV001851790, RCV002490353" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011319...</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>See <a href="#93" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Buerstedde, J.-M., Sommer, S. S. <strong>Functionally important regions of the factor IX gene have a low rate of polymorphism and a high rate of mutation in the dinucleotide CpG.</strong> Am. J. Hum. Genet. 45: 448-457, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2773937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2773937</a>]" pmid="2773937">Koeberl et al. (1989)</a> and <a href="#182" class="mim-tip-reference" title="Zhang, M., Chen, S.-H., Thompson, A. R., Lovrien, E., Scott, C. R. <strong>CG dinucleotides are 'hot spots' in the factor IX gene for point mutations: evidence from the study of 25 families with defined mutations causing hemophilia B. (Abstract)</strong> Am. J. Hum. Genet. 45: A231, 1989."None>Zhang et al. (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically mild. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2773937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="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 B</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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F9, GLU33ASP
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852229 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852229;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=rs137852229" 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=rs137852229" 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=RCV000011320" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011320" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011320</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>See <a href="#93" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Buerstedde, J.-M., Sommer, S. S. <strong>Functionally important regions of the factor IX gene have a low rate of polymorphism and a high rate of mutation in the dinucleotide CpG.</strong> Am. J. Hum. Genet. 45: 448-457, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2773937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2773937</a>]" pmid="2773937">Koeberl et al. (1989)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2773937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="0018" class="mim-anchor"></a>
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<strong>.0018 HEMOPHILIA B</strong>
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F9, IVS3DS, T-G
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011409" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011409" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011409</a>
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<p><a href="#31" class="mim-tip-reference" title="Brownlee, G. G. <strong>Haemophilia B: a review of patient defects, diagnosis with gene probes and prospects for gene therapy.</strong> Recent Adv. Haemat. 5: 251-265, 1988."None>Brownlee (1988)</a> described a GT-to-GG donor splice site mutation in IVS3 in association with severe hemophilia B (<a href="/entry/306900">306900</a>).</p>
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<a id="0019" class="mim-anchor"></a>
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<strong>.0019 HEMOPHILIA B</strong>
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F9, ASP47GLY
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852230 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852230;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=rs137852230" 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=rs137852230" 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=RCV000011322" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011322" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011322</a>
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<p>Davis et al. (<a href="#55" class="mim-tip-reference" title="Davis, L. M., McGraw, R. A., Graham, J. B., Roberts, H. R., Stafford, D. W. <strong>Identification of the genetic defect in factor IX (Alabama): DNA sequence analysis reveals a gly substitution for asp(46). (Abstract)</strong> Blood 64 (suppl.): 262a, 1984."None>1984</a>, <a href="#56" class="mim-tip-reference" title="Davis, L. M., McGraw, R. A., Ware, J. L., Roberts, H. R., Stafford, D. W. <strong>Factor IX (Alabama): a point mutation in a clotting protein results in hemophilia B.</strong> Blood 69: 140-143, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3790720/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3790720</a>]" pmid="3790720">1987</a>) found that factor IX Alabama, a CRM+ mutation responsible for a clinically moderate form of hemophilia B (<a href="/entry/306900">306900</a>), has an adenine to guanine transition in the first nucleotide of exon d, causing substitution of glycine for aspartic acid (GAT to GGT) at residue 47. The structural defect in factor IX Alabama results in a molecule with 10% of normal coagulant activity. <a href="#115" class="mim-tip-reference" title="McCord, D. M., Monroe, D. M., Smith, K. J., Roberts, H. R. <strong>Characterization of the functional defect in factor IX Alabama: evidence for a conformational change due to high affinity calcium binding in the first epidermal growth factor domain.</strong> J. Biol. Chem. 265: 10250-10254, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2355000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2355000</a>]" pmid="2355000">McCord et al. (1990)</a> concluded that the asp47-to-gly mutation, which occurs in a calcium-binding site, results in a loss of a stable calcium-mediated conformational change, leading to improper interaction with factor VIIIa and factor X. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3790720+2355000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="0020" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0020 HEMOPHILIA B</strong>
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F9, GLN50PRO
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852231 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852231;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=rs137852231" 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=rs137852231" 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=RCV000011323 OR RCV004783723" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011323, RCV004783723" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011323...</a>
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</span>
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<span class="mim-text-font">
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<p>See <a href="#107" class="mim-tip-reference" title="Lozier, B. N., Stanfield-Oakley, S. A., High, K. A. <strong>Factor IX New London: a point mutation causing hemophilia B. (Abstract)</strong> Thromb. Haemost. 62: 162, 1989."None>Lozier et al. (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically severe.</p>
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<br />
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<a id="0021" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0021 HEMOPHILIA B</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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F9, PRO55ALA
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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> rs137852232 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852232;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/rs137852232?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=rs137852232" 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=rs137852232" 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=RCV000011324 OR RCV001810845 OR RCV003764550" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011324, RCV001810845, RCV003764550" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011324...</a>
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<span class="mim-text-font">
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<p>This variant has been designated factor IX Hollywood.</p><p>See <a href="#75" class="mim-tip-reference" title="Green, P. M., Bentley, D. R., Mibashan, R. S., Nilsson, I. M., Giannelli, F. <strong>Molecular pathology of haemophilia B.</strong> EMBO J. 8: 1067-1072, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2743975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2743975</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1989.tb03474.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2743975">Green et al. (1989)</a> and <a href="#147" class="mim-tip-reference" title="Spitzer, S., Katzman, D., Kasper, C., Bajaj, S. P. <strong>Factor IX Hollywood: substitution of 55 pro-to-ala in the first EGF domain. (Abstract)</strong> Thromb. Haemost. 62: 203, 1989."None>Spitzer et al. (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically mild. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2743975" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="0022" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0022 HEMOPHILIA B</strong>
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F9, GLY60SER
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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> rs137852233 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852233;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/rs137852233?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=rs137852233" 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=rs137852233" 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=RCV000011325 OR RCV000795416 OR RCV001810846 OR RCV002247325 OR RCV002496325 OR RCV003430636" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011325, RCV000795416, RCV001810846, RCV002247325, RCV002496325, RCV003430636" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011325...</a>
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<p>This variant has been designated factor IX Durham.</p><p>In 2 men with mild hemophilia B (<a href="/entry/306900">306900</a>), <a href="#57" class="mim-tip-reference" title="Denton, P. H., Fowlkes, D. M., Lord, S. T., Reisner, H. M. <strong>Hemophilia B Durham: a mutation in the first EGF-like domain of factor IX that is characterized by polymerase chain reaction.</strong> Blood 72: 1407-1411, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3262389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3262389</a>]" pmid="3262389">Denton et al. (1988)</a> found that the highly conserved gly60 residue had been changed to ser. The mutation was accompanied by defective epitope expression in the 2 patients, suggesting that a change in the tertiary structure of the EGF-like domain is the cause of the mild hemophilia B. See <a href="#39" class="mim-tip-reference" title="Chen, S.-H., Scott, C. R., Schoof, J., Lovrien, E. W., Kurachi, K. <strong>Factor IX(Portland): a nonsense mutation (CGA to TGA) resulting in hemophilia B.</strong> Am. J. Hum. Genet. 44: 567-569, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2929599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2929599</a>]" pmid="2929599">Chen et al. (1989)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3262389+2929599" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#128" class="mim-tip-reference" title="Poort, S. R., Briet, E., Bertina, R. M., Reitsma, P. H. <strong>A Dutch pedigree with mild hemophilia B with a missense mutation in the first EGF domain [factor IX(Oud en Nieuw Gastel)].</strong> Nucleic Acids Res. 17: 5869, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2762170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2762170</a>] [<a href="https://doi.org/10.1093/nar/17.14.5869" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2762170">Poort et al. (1989)</a> found the same mutation in a Dutch family. A G-to-A change at position 10430 in exon 4 was responsible. The presence of the same mutation in 3 patients from distinct geographic areas confirmed the notion that CpG dinucleotides are 'hotspots' for mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2762170" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="0023" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0023 HEMOPHILIA B</strong>
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</span>
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</h4>
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</div>
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F9, ASP64GLY
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852234 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852234;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=rs137852234" 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=rs137852234" 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=RCV000011326" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011326" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011326</a>
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<p>See <a href="#75" class="mim-tip-reference" title="Green, P. M., Bentley, D. R., Mibashan, R. S., Nilsson, I. M., Giannelli, F. <strong>Molecular pathology of haemophilia B.</strong> EMBO J. 8: 1067-1072, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2743975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2743975</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1989.tb03474.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2743975">Green et al. (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically mild. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2743975" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0024 HEMOPHILIA B</strong>
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F9, GLY114ALA
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852235 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852235;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=rs137852235" 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=rs137852235" 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=RCV000011327" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011327" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011327</a>
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<p>See <a href="#178" class="mim-tip-reference" title="Winship, P. R., Rees, D. J. G., Alkan, M. <strong>Detection of polymorphisms at cytosine phosphoguanidine dinucleotides and diagnosis of haemophilia B carriers.</strong> Lancet 333: 631-634, 1989. Note: Originally Volume 1.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2564457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2564457</a>] [<a href="https://doi.org/10.1016/s0140-6736(89)92141-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2564457">Winship et al. (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically severe. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2564457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 B</strong>
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</h4>
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F9, ASN120TYR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852236 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852236;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=rs137852236" 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=rs137852236" 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=RCV000011328" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011328" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011328</a>
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<p>See <a href="#75" class="mim-tip-reference" title="Green, P. M., Bentley, D. R., Mibashan, R. S., Nilsson, I. M., Giannelli, F. <strong>Molecular pathology of haemophilia B.</strong> EMBO J. 8: 1067-1072, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2743975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2743975</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1989.tb03474.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2743975">Green et al. (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically severe. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2743975" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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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<span class="mim-font">
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<strong>.0026 HEMOPHILIA B</strong>
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F9, ARG145CYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894807 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894807;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=rs104894807" 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=rs104894807" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <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> rs137852237 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852237;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/rs137852237?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=rs137852237" 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=rs137852237" 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=RCV000011330 OR RCV001390295 OR RCV004700216 OR RCV005042030" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011330, RCV001390295, RCV004700216, RCV005042030" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011330...</a>
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<p><a href="#103" class="mim-tip-reference" title="Liddell, M. B., Peake, I. R., Taylor, S. A. M., Lillicrap, D. P., Giddings, J. C., Bloom, A. L. <strong>Factor IX Cardiff: a variant factor IX protein that shows abnormal activation is caused by an arginine to cysteine substitution at position 145.</strong> Brit. J. Haemat. 72: 556-560, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2775660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2775660</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1989.tb04323.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2775660">Liddell et al. (1989)</a> described a molecular defect in factor IX Cardiff, a variant that showed faulty activation with the production of a stable reaction product with a molecular weight compatible with that of a putative light chain-activation intermediate. A single C-to-T transition was discovered that changed the arg residue at position 145 (the first residue of the first bond in the activation peptide) to a cys. The hemophilia (<a href="/entry/306900">306900</a>) was clinically moderate to severe. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2775660" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 HEMOPHILIA B</strong>
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</h4>
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F9, ARG145HIS
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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> rs137852238 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852238;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/rs137852238?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=rs137852238" 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=rs137852238" 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=RCV000011331 OR RCV000851602 OR RCV001390296 OR RCV002247326 OR RCV002284168" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011331, RCV000851602, RCV001390296, RCV002247326, RCV002284168" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011331...</a>
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<span class="mim-text-font">
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<p>Factor IX Chapel Hill, a CRM+ variant of mild hemophilia B (<a href="/entry/306900">306900</a>), results from an arg-to-his change at residue 145, which prevents cleavage at one of the activation sites (<a href="#120" class="mim-tip-reference" title="Noyes, C. M., Griffith, M. J., Roberts, H. R., Lundblad, R. L. <strong>Identification of the molecular defect in factor IX(Chapel Hill): substitution of histidine for arginine at position 145.</strong> Proc. Nat. Acad. Sci. 80: 4200-4202, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6603618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6603618</a>] [<a href="https://doi.org/10.1073/pnas.80.14.4200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6603618">Noyes et al., 1983</a>). See <a href="#93" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Buerstedde, J.-M., Sommer, S. S. <strong>Functionally important regions of the factor IX gene have a low rate of polymorphism and a high rate of mutation in the dinucleotide CpG.</strong> Am. J. Hum. Genet. 45: 448-457, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2773937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2773937</a>]" pmid="2773937">Koeberl et al. (1989)</a>. <a href="#149" class="mim-tip-reference" title="Suehiro, K., Miyata, T., Takeya, H., Takamatsu, J., Saito, H., Murakawa, M., Okamura, T., Niho, Y., Iwanaga, S. <strong>Blood clotting factor IX Nagoya 3: the molecular defect of zymogen activation caused by an arginine-145 to histidine substitution.</strong> Thromb. Res. 60: 311-320, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2087690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2087690</a>] [<a href="https://doi.org/10.1016/0049-3848(90)90109-p" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2087690">Suehiro et al. (1990)</a> concluded that the arg145-to-his substitution impairs the cleavage between the light chain and the activation peptide by factor XIa/calcium ions. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2087690+6603618+2773937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 variant has also been called factor IX Nagoya-3.</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 DEEP VENOUS THROMBOSIS, PROTECTION AGAINST</strong>
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</h4>
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F9, THR148ALA
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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> rs6048 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs6048;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/rs6048?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=rs6048" 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=rs6048" 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=RCV000011334 OR RCV000244191 OR RCV000396693 OR RCV001521358 OR RCV001701639 OR RCV001810847" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011334, RCV000244191, RCV000396693, RCV001521358, RCV001701639, RCV001810847" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011334...</a>
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<p><a href="#116" class="mim-tip-reference" title="McGraw, R. A., Davis, L. M., Noyes, C. M., Lundblad, R. L., Roberts, H. R., Graham, J. B., Stafford, D. W. <strong>Evidence for a prevalent dimorphism in the activation peptide of human coagulation factor IX.</strong> Proc. Nat. Acad. Sci. 82: 2847-2851, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3857619/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3857619</a>] [<a href="https://doi.org/10.1073/pnas.82.9.2847" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3857619">McGraw et al. (1985)</a> identified a common polymorphism at the third amino acid residue in the activation peptide of the F9 gene: an A-to-G transition resulting in a thr148-to-ala (T148A) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3857619" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#176" class="mim-tip-reference" title="Winship, P. R., Brownlee, G. G. <strong>Diagnosis of haemophilia B carriers using intragenic oligonucleotide probes. (Letter)</strong> Lancet 328: 218-219, 1986. Note: Originally Volume 2.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2873459/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2873459</a>] [<a href="https://doi.org/10.1016/s0140-6736(86)92513-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2873459">Winship and Brownlee (1986)</a> also identified the 20422A-G transition in the F9 gene and found that it gave rise to an MnlI RFLP. However, technical problems made it difficult to detect the polymorphic fragments by conventional Southern blotting. The polymorphism as identified by oligonucleotide probes was used for linkage studies in a 3-generation family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2873459" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#72" class="mim-tip-reference" title="Graham, J. B., Lubahn, D. B., Lord, S. T., Kirshtein, J., Nilsson, I. M., Wallmark, A., Ljung, R., Frazier, L. D., Ware, J. L., Lin, S. W., Stafford, D. W., Bosco, J. <strong>The Malmo polymorphism of coagulation factor IX, an immunologic polymorphism due to dimorphism of residue 148 that is in linkage disequilibrium with two other F.IX polymorphisms.</strong> Am. J. Hum. Genet. 42: 573-580, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2450455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2450455</a>]" pmid="2450455">Graham et al. (1988)</a> showed that the F9 protein with thr148 reacted to the mouse monoclonal antibody, whereas that with ala148 did not. The polymorphism is referred to as the F9 Malmo polymorphism; positive reactors are designated Malmo A, and negative reactors are designated Malmo B. Strong linkage disequilibrium was found with 2 other intragenic RFLPs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2450455" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#16" class="mim-tip-reference" title="Bezemer, I. D., Bare, L. A., Doggen, C. J. M., Arellano, A. R., Tong, C., Rowland, C. M., Catanese, J., Young, B. A., Reitsma, P. H., Devlin, J. J., Rosendaal, F. R. <strong>Gene variants associated with deep vein thrombosis.</strong> JAMA 299: 1306-1314, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18349091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18349091</a>] [<a href="https://doi.org/10.1001/jama.299.11.1306" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18349091">Bezemer et al. (2008)</a> reported that the G allele (ala148) of F9 Malmo (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs6048;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs6048</a>) was associated with a 15 to 43% decrease in deep vein thrombosis risk compared to the A allele in 3 case-control studies of deep vein thrombosis. This common variant has a minor allele frequency of 0.32. The substitution occurs in the portion of the factor IX zymogen that is cleaved from the zymogen to activate factor IX. The authors noted that this variant had not been reported to be associated with hemophilia B (<a href="/entry/306900">306900</a>). In a follow-up study from 3 case-control studies involving a total of 1,445 male patients with deep venous thrombosis and 2,351 male controls, <a href="#15" class="mim-tip-reference" title="Bezemer, I. D., Arellano, A. R., Tong, C. H., Rowland, C. M., Ireland, H. A., Bauer, K. A., Catanese, J., Reitsma, P. H., Doggen, C. J. M., Devlin, J. J., Rosendaal, F. R., Bare, L. A. <strong>F9 Malmo, factor IX and deep vein thrombosis.</strong> Haematologica 94: 693-699, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19286883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19286883</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19286883[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/10.3324/haematol.2008.003020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19286883">Bezemer et al. (2009)</a> found that the G allele of F9 Malmo conferred protection against deep venous thrombosis (odds ratio of 0.80); see <a href="/entry/300807">300807</a>. The pooled corresponding odds ratio in a comparable number of women with deep venous thrombosis was 0.89. However, factor IX antigen level, factor IX activation peptide levels, and endogenous thrombin potential did not differ between the F9 Malmo genotypes. Although F9 Malmo was the most strongly associated with protection from deep vein thrombosis, the biologic mechanism remained unknown. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19286883+18349091" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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">rs137852239 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852239;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=rs137852239" 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=rs137852239" 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=RCV000011335" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011335" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011335</a>
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<p>See <a href="#93" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Buerstedde, J.-M., Sommer, S. S. <strong>Functionally important regions of the factor IX gene have a low rate of polymorphism and a high rate of mutation in the dinucleotide CpG.</strong> Am. J. Hum. Genet. 45: 448-457, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2773937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2773937</a>]" pmid="2773937">Koeberl et al. (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically severe. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2773937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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">rs137852240 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852240;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=rs137852240" 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=rs137852240" 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=RCV000011336 OR RCV001810848 OR RCV002512970 OR RCV003407315" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011336, RCV001810848, RCV002512970, RCV003407315" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011336...</a>
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<p>This variant has been called factor IX B(M) Nagoya and factor IX Deventer.</p><p><a href="#148" class="mim-tip-reference" title="Suehiro, K., Kawabata, S., Miyata, T., Takeya, H., Takamatsu, J., Ogata, K., Kamiya, T., Saito, H., Niho, Y., Iwanaga, S. <strong>Blood clotting factor IX B(M) Nagoya: substitution of arginine 180 by tryptophan and its activation by alpha-chymotrypsin and rat mast cell chymase.</strong> J. Biol. Chem. 264: 21257-21265, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2592373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2592373</a>]" pmid="2592373">Suehiro et al. (1989)</a> demonstrated substitution of tryptophan for arginine at position 180 in the factor IX protein of a patient with severe hemophilia B (<a href="/entry/306900">306900</a>). <a href="#11" class="mim-tip-reference" title="Bertina, R. M., van der Linden, I. K., Mannucci, P. M., Reinalda-Poot, H. H., Cupers, R., Poort, S. R., Reitsma, P. H. <strong>Mutations in hemophilia B(m) occur at the arg(180)-to-val activation site or in the catalytic domain of factor IX.</strong> J. Biol. Chem. 265: 10876-10883, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2162822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2162822</a>]" pmid="2162822">Bertina et al. (1990)</a> found the same mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2592373+2162822" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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">rs137852241 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852241;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=rs137852241" 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=rs137852241" 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=RCV000011337 OR RCV001727513 OR RCV004752695 OR RCV004814880" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011337, RCV001727513, RCV004752695, RCV004814880" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011337...</a>
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<p>This variant has been called factor IX Hilo and factor IX Novara.</p><p>A subset of hemophilia B patients have a prolonged prothrombin time (PT) when exposed to bovine (or ox) brain tissue; these CRM+ patients are classified as having hemophilia B(M) (see <a href="/entry/306900">306900</a>). <a href="#84" class="mim-tip-reference" title="Huang, M.-N., Kasper, C. K., Roberts, H. R., Stafford, D. W., High, K. A. <strong>Molecular defect in factor IX(Hilo), a hemophilia B(m) variant: arg-to-gln at the carboxyterminal cleavage site of the activation peptide.</strong> Blood 73: 718-721, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2563663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2563663</a>]" pmid="2563663">Huang et al. (1989)</a> demonstrated a point mutation in a hemophilia B(M) variant, factor IX Hilo. Glutamine (CAG) was substituted for arginine (CGG) at amino acid 180 in exon 6 (G-to-A at nucleotide 20519). <a href="#11" class="mim-tip-reference" title="Bertina, R. M., van der Linden, I. K., Mannucci, P. M., Reinalda-Poot, H. H., Cupers, R., Poort, S. R., Reitsma, P. H. <strong>Mutations in hemophilia B(m) occur at the arg(180)-to-val activation site or in the catalytic domain of factor IX.</strong> J. Biol. Chem. 265: 10876-10883, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2162822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2162822</a>]" pmid="2162822">Bertina et al. (1990)</a> found the same mutation. The hemophilia was clinically severe. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2563663+2162822" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#101" class="mim-tip-reference" title="Lefkowitz, J. B., Monroe, D. M., Kasper, C. K., Roberts, H. R. <strong>Comparison of the behavior of normal factor IX and the factor IX BM variant Hilo in the prothrombin time test using tissue factors from bovine, human, and rabbit sources.</strong> Am. J. Hemat. 43: 177-182, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8352232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8352232</a>] [<a href="https://doi.org/10.1002/ajh.2830430304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8352232">Lefkowitz et al. (1993)</a> noted that the bovine brain tissue in studies of hemophilia B(M) is the source of thromboplastin, or tissue factor (F3; <a href="/entry/134390">134390</a>); PT times determined with thromboplastin from rabbit brain or human brain are not reported to be prolonged. However, in various studies of factor IX Hilo, <a href="#101" class="mim-tip-reference" title="Lefkowitz, J. B., Monroe, D. M., Kasper, C. K., Roberts, H. R. <strong>Comparison of the behavior of normal factor IX and the factor IX BM variant Hilo in the prothrombin time test using tissue factors from bovine, human, and rabbit sources.</strong> Am. J. Hemat. 43: 177-182, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8352232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8352232</a>] [<a href="https://doi.org/10.1002/ajh.2830430304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8352232">Lefkowitz et al. (1993)</a> found that either normal F9 or Hilo F9 prolonged the PT regardless of the tissue factor source, but the prolongation required high concentrations of factor IX when rabbit or human brain was used. With bovine thromboplastin, factor IX Hilo was significantly better than normal factor IX at prolonging the PT. In addition, the prolongation times depended on the amounts of factors IX and X used in the assays. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8352232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0032 HEMOPHILIA B</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">rs387906477 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906477;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=rs387906477" 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=rs387906477" 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=RCV000011338" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011338" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011338</a>
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<p>This variant has been designated factor IX Milano. See Bertina et al. (<a href="#10" class="mim-tip-reference" title="Bertina, R. M., van der Linden, I. K., Mannucci, P. M., Reinalda-Poot, H. H., Cupers, R., Poort, S. R., Reitsma, P. H. <strong>Mutations in haemophilia B-M occur at the 180arg-to-val activation site or in the catalytic domain. (Abstract)</strong> Thromb. Haemost. 62: 203, 1989."None>1989</a>, <a href="#11" class="mim-tip-reference" title="Bertina, R. M., van der Linden, I. K., Mannucci, P. M., Reinalda-Poot, H. H., Cupers, R., Poort, S. R., Reitsma, P. H. <strong>Mutations in hemophilia B(m) occur at the arg(180)-to-val activation site or in the catalytic domain of factor IX.</strong> J. Biol. Chem. 265: 10876-10883, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2162822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2162822</a>]" pmid="2162822">1990</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2162822" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0033 HEMOPHILIA B</strong>
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F9, VAL182PHE
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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> rs137852243 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852243;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/rs137852243?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=rs137852243" 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=rs137852243" 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=RCV000011339" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011339" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011339</a>
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<p><a href="#136" class="mim-tip-reference" title="Sakai, T., Yoshioka, A., Yamamoto, K., Niinomi, K., Fujimura, Y., Fukui, H., Miyata, T., Iwanaga, S. <strong>Blood clotting factor IX Kashihara: amino acid substitution of valine-182 by phenylalanine.</strong> J. Biochem. 105: 756-759, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2753873/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2753873</a>] [<a href="https://doi.org/10.1093/oxfordjournals.jbchem.a122740" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2753873">Sakai et al. (1989)</a> found that the defect in hemophilia B (<a href="/entry/306900">306900</a>) (factor IX Kashihara), a severe hemorrhagic disorder in which a factor IX antigen is present in normal amounts but factor IX biological activity is markedly reduced, has a defect in valine-182 (equivalent to valine-17 in the chymotrypsin numbering system), which is replaced by phenylalanine. The change appears to hinder sterically the cleavage of arg180-val181 required for the activation of this zymogen. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2753873" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0034 HEMOPHILIA B(M)</strong>
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F9, VAL182LEU
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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> rs137852243 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852243;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/rs137852243?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=rs137852243" 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=rs137852243" 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=RCV000011340" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011340" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011340</a>
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<p>This variant has been designated factor IX Cardiff II. See <a href="#156" class="mim-tip-reference" title="Taylor, S. A. M., Liddell, M. B., Peake, I. R., Lillicrap, D. P. <strong>Mutations affecting cleavage of the activation peptide of factor IX as a cause of hemophilia B. (Abstract)</strong> Am. J. Hum. Genet. 45: A223, 1989."None>Taylor et al. (1989)</a>. One of the variant forms of hemophilia B in which normal levels of a dysfunctional factor IX protein is found is referred to as hemophilia B(M) (see <a href="/entry/306900">306900</a>) (<a href="#83" class="mim-tip-reference" title="Hougie, C., Twomey, J. J. <strong>Hemophilia B(M): a new type of factor-IX deficiency.</strong> Lancet 289: 698-700, 1967. Note: Originally Volume 1.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4163943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4163943</a>] [<a href="https://doi.org/10.1016/s0140-6736(67)92179-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4163943">Hougie and Twomey, 1967</a>; <a href="#86" class="mim-tip-reference" title="Kasper, C. K., Osterud, B., Minami, J. Y., Schonick, W., Rapaport, S. I. <strong>Hemophilia B--characterization of genetic variants and detection of carriers.</strong> Blood 50: 351-366, 1977.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/884315/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">884315</a>]" pmid="884315">Kasper et al., 1977</a>). The abnormal factor IX results in prolongation of the prothrombin time performed with ox brain thromboplastin. In 1 such patient, <a href="#155" class="mim-tip-reference" title="Taylor, S. A. M., Liddell, M. B., Peake, I. R., Bloom, A. L., Lillicrap, D. P. <strong>A mutation adjacent to the beta cleavage site of factor IX (valine 182 to leucine) results in mild haemophilia B(m).</strong> Brit. J. Haemat. 75: 217-221, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2372509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2372509</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1990.tb02652.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2372509">Taylor et al. (1990)</a> found a G-to-C transversion at nucleotide 20524, changing the amino acid encoded at residue 182 from valine to leucine. The abnormal factor IX protein showed a normal molecular weight and normal calcium-binding properties. Activation of the mutant factor IX with factor XIa showed normal proteolytic cleavage. Hemophilia was clinically mild in these patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2372509+884315+4163943" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0035 HEMOPHILIA B</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">rs137852244 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852244;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=rs137852244" 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=rs137852244" 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=RCV000011341" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011341" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011341</a>
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<p>See <a href="#111" class="mim-tip-reference" title="Matsushita, T., Tanimoto, M., Yamamoto, K., Sugiura, I., Hamaguchi, M., Takamatsu, J., Saito, H. <strong>Nucleotide sequence analysis of hemophilia B with the inhibitor phenotype. (Abstract)</strong> Blood 74: 251A, 1989."None>Matsushita et al. (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically severe.</p>
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<strong>.0036 HEMOPHILIA B</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">rs137852245 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852245;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=rs137852245" 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=rs137852245" 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=RCV000011342" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011342" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011342</a>
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<span class="mim-text-font">
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<p>Information was provided by <a href="#41" class="mim-tip-reference" title="Chen, S.-H., Thompson, A. R. <strong>Personal Communication.</strong> Seattle, Wash. 11/1989."None>Chen and Thompson (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically severe.</p>
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<a id="0037" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0037 HEMOPHILIA B</strong>
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F9, TRP194TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1603265827 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1603265827;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=rs1603265827" 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=rs1603265827" 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=RCV001001415 OR RCV002282420" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001001415, RCV002282420" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001001415...</a>
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</span>
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<span class="mim-text-font">
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<p>See <a href="#75" class="mim-tip-reference" title="Green, P. M., Bentley, D. R., Mibashan, R. S., Nilsson, I. M., Giannelli, F. <strong>Molecular pathology of haemophilia B.</strong> EMBO J. 8: 1067-1072, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2743975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2743975</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1989.tb03474.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2743975">Green et al. (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically severe. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2743975" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="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 B</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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F9, IVS6DS, G-T
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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">rs1603265832 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1603265832;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=rs1603265832" 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=rs1603265832" 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=RCV000011343" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011343" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011343</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 severely affected, antigen-negative (CRM-negative) patient with hemophilia B (<a href="/entry/306900">306900</a>), <a href="#129" class="mim-tip-reference" title="Rees, D. J. G., Rizza, C. R., Brownlee, G. G. <strong>Haemophilia B caused by a point mutation in a donor splice junction of the human factor IX gene.</strong> Nature 316: 643-645, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4033760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4033760</a>] [<a href="https://doi.org/10.1038/316643a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4033760">Rees et al. (1985)</a> found a point mutation in the F9 gene that changed an obligatory GT to a TT within the donor splice junction of exon 6. This was comparable to point mutations in splice junctions that lead to beta-zero-thalassemia (see <a href="/entry/613985">613985</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4033760" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="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 B</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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F9, TRP215TER
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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=RCV000011344" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011344" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011344</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>Information was provided by <a href="#41" class="mim-tip-reference" title="Chen, S.-H., Thompson, A. R. <strong>Personal Communication.</strong> Seattle, Wash. 11/1989."None>Chen and Thompson (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically severe.</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="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 B</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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F9, CYS222TRP
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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">rs137852246 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852246;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=rs137852246" 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=rs137852246" 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=RCV000011345" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011345" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011345</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>See <a href="#93" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Buerstedde, J.-M., Sommer, S. S. <strong>Functionally important regions of the factor IX gene have a low rate of polymorphism and a high rate of mutation in the dinucleotide CpG.</strong> Am. J. Hum. Genet. 45: 448-457, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2773937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2773937</a>]" pmid="2773937">Koeberl et al. (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically moderate in severity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2773937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="0041" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong><div class="mim-changed mim-change">.0041 F9 POLYMORPHISM</div></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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F9, VAL227VAL
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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> rs1800455 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1800455;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/rs1800455?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=rs1800455" 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=rs1800455" 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=RCV000011346 OR RCV000402083 OR RCV001086730 OR RCV003934824 OR RCV004703182" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011346, RCV000402083, RCV001086730, RCV003934824, RCV004703182" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011346...</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 T-to-C substitution in codon 227 produced no change in amino acid (<a href="#93" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Buerstedde, J.-M., Sommer, S. S. <strong>Functionally important regions of the factor IX gene have a low rate of polymorphism and a high rate of mutation in the dinucleotide CpG.</strong> Am. J. Hum. Genet. 45: 448-457, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2773937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2773937</a>]" pmid="2773937">Koeberl et al., 1989</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2773937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="0042" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0042 HEMOPHILIA B</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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F9, ALA233THR
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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">rs387906478 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906478;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=rs387906478" 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=rs387906478" 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=RCV000011347" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011347" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011347</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>See <a href="#93" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Buerstedde, J.-M., Sommer, S. S. <strong>Functionally important regions of the factor IX gene have a low rate of polymorphism and a high rate of mutation in the dinucleotide CpG.</strong> Am. J. Hum. Genet. 45: 448-457, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2773937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2773937</a>]" pmid="2773937">Koeberl et al. (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically mild. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2773937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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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<a id="0043" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0043 HEMOPHILIA B</strong>
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</h4>
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F9, IVS7AS, G-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">rs1439169192 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1439169192;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=rs1439169192" 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=rs1439169192" 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=RCV001812588 OR RCV001815042 OR RCV003772215" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001812588, RCV001815042, RCV003772215" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001812588...</a>
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<p><a href="#111" class="mim-tip-reference" title="Matsushita, T., Tanimoto, M., Yamamoto, K., Sugiura, I., Hamaguchi, M., Takamatsu, J., Saito, H. <strong>Nucleotide sequence analysis of hemophilia B with the inhibitor phenotype. (Abstract)</strong> Blood 74: 251A, 1989."None>Matsushita et al. (1989)</a> found a G-to-A substitution in the last nucleotide in the 3-prime acceptor splice site of IVS7. The hemophilia (<a href="/entry/306900">306900</a>) was severe and was associated with a serum inhibitor.</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 B</strong>
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</span>
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</h4>
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</div>
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F9, ARG248TER
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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> rs137852248 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852248;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/rs137852248?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=rs137852248" 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=rs137852248" 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=RCV000011333 OR RCV001000167 OR RCV001069256 OR RCV004791215" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011333, RCV001000167, RCV001069256, RCV004791215" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011333...</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>See <a href="#75" class="mim-tip-reference" title="Green, P. M., Bentley, D. R., Mibashan, R. S., Nilsson, I. M., Giannelli, F. <strong>Molecular pathology of haemophilia B.</strong> EMBO J. 8: 1067-1072, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2743975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2743975</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1989.tb03474.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2743975">Green et al. (1989)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2743975" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="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 B</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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F9, ARG248GLN
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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">rs137852249 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852249;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=rs137852249" 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=rs137852249" 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=RCV000011348 OR RCV000814168 OR RCV000851909 OR RCV004724733" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011348, RCV000814168, RCV000851909, RCV004724733" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011348...</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>This variant has been called factor IX Seattle-4 and factor IX Dreihacken.</p><p>See <a href="#39" class="mim-tip-reference" title="Chen, S.-H., Scott, C. R., Schoof, J., Lovrien, E. W., Kurachi, K. <strong>Factor IX(Portland): a nonsense mutation (CGA to TGA) resulting in hemophilia B.</strong> Am. J. Hum. Genet. 44: 567-569, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2929599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2929599</a>]" pmid="2929599">Chen et al. (1989)</a>. In a patient with hemophilia B (<a href="/entry/306900">306900</a>), <a href="#108" class="mim-tip-reference" title="Ludwig, M., Sabharwal, A. K., Brackmann, H. H., Olek, K., Smith, K. J., Birktoft, J. J., Bajaj, S. P. <strong>Hemophilia B caused by five different nondeletion mutations in the protease domain of factor IX.</strong> Blood 79: 1225-1232, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1346975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1346975</a>]" pmid="1346975">Ludwig et al. (1992)</a> identified a G-to-A transition at nucleotide 30864 of the F9 gene, resulting in replacement of arg248 by gln in the mature factor IX protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1346975+2929599" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="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 B</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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F9, ARG252TER
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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">rs137852250 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852250;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=rs137852250" 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=rs137852250" 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=RCV000011349 OR RCV001001417 OR RCV002512971 OR RCV004819206" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011349, RCV001001417, RCV002512971, RCV004819206" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011349...</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 male sibs with severe hemophilia B (<a href="/entry/306900">306900</a>), <a href="#39" class="mim-tip-reference" title="Chen, S.-H., Scott, C. R., Schoof, J., Lovrien, E. W., Kurachi, K. <strong>Factor IX(Portland): a nonsense mutation (CGA to TGA) resulting in hemophilia B.</strong> Am. J. Hum. Genet. 44: 567-569, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2929599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2929599</a>]" pmid="2929599">Chen et al. (1989)</a> demonstrated a C-to-T change at nucleotide 30875 resulting in a nonsense mutation (TGA) and termination of protein synthesis at amino acid residue 252. The change involved a CpG dinucleotide. The protein was designated factor IX Portland. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2929599" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="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 B</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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F9, ASN260SER
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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">rs137852251 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852251;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=rs137852251" 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=rs137852251" 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=RCV000011350" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011350" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011350</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>See <a href="#93" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Buerstedde, J.-M., Sommer, S. S. <strong>Functionally important regions of the factor IX gene have a low rate of polymorphism and a high rate of mutation in the dinucleotide CpG.</strong> Am. J. Hum. Genet. 45: 448-457, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2773937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2773937</a>]" pmid="2773937">Koeberl et al. (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically mild. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2773937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="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 B</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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F9, PRO287LEU
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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">rs137852252 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852252;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=rs137852252" 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=rs137852252" 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=RCV000011351" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011351" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011351</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>Information was provided by <a href="#41" class="mim-tip-reference" title="Chen, S.-H., Thompson, A. R. <strong>Personal Communication.</strong> Seattle, Wash. 11/1989."None>Chen and Thompson (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically severe.</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="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 B</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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F9, ALA291PRO
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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">rs137852253 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852253;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=rs137852253" 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=rs137852253" 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=RCV000011352" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011352" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011352</a>
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<p>See <a href="#178" class="mim-tip-reference" title="Winship, P. R., Rees, D. J. G., Alkan, M. <strong>Detection of polymorphisms at cytosine phosphoguanidine dinucleotides and diagnosis of haemophilia B carriers.</strong> Lancet 333: 631-634, 1989. Note: Originally Volume 1.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2564457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2564457</a>] [<a href="https://doi.org/10.1016/s0140-6736(89)92141-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2564457">Winship et al. (1989)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2564457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0050 HEMOPHILIA B</strong>
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F9, THR296MET
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852254 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852254;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=rs137852254" 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=rs137852254" 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=RCV000011353 OR RCV000792734 OR RCV000851963 OR RCV001810849 OR RCV004752696 OR RCV005042031" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011353, RCV000792734, RCV000851963, RCV001810849, RCV004752696, RCV005042031" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011353...</a>
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<p>See <a href="#93" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Buerstedde, J.-M., Sommer, S. S. <strong>Functionally important regions of the factor IX gene have a low rate of polymorphism and a high rate of mutation in the dinucleotide CpG.</strong> Am. J. Hum. Genet. 45: 448-457, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2773937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2773937</a>]" pmid="2773937">Koeberl et al. (1989)</a>. Hemophilia B (<a href="/entry/306900">306900</a>) is an X-linked disorder relatively frequent among the Amish, particularly those living in Ohio (<a href="#170" class="mim-tip-reference" title="Wall, R. L., McConnell, J., Moore, D., Macpherson, C. R., Marson, A. <strong>Christmas disease, color-blindness and blood group Xg(a).</strong> Am. J. Med. 43: 214-226, 1967.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5298508/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5298508</a>] [<a href="https://doi.org/10.1016/0002-9343(67)90166-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5298508">Wall et al., 1967</a>). <a href="#88" class="mim-tip-reference" title="Ketterling, R. P., Bottema, C. D. K., Koeberl, D. D., Ii, S., Sommer, S. S. <strong>T-296-to-M, a common mutation causing mild hemophilia B in the Amish and others: founder effect, variability in factor IX activity assays, and rapid carrier detection.</strong> Hum. Genet. 87: 333-337, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1864609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1864609</a>] [<a href="https://doi.org/10.1007/BF00200915" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1864609">Ketterling et al. (1991)</a> demonstrated that the Amish mutation is thr296-to-met. Among 64 families of European descent with hemophilia B, <a href="#88" class="mim-tip-reference" title="Ketterling, R. P., Bottema, C. D. K., Koeberl, D. D., Ii, S., Sommer, S. S. <strong>T-296-to-M, a common mutation causing mild hemophilia B in the Amish and others: founder effect, variability in factor IX activity assays, and rapid carrier detection.</strong> Hum. Genet. 87: 333-337, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1864609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1864609</a>] [<a href="https://doi.org/10.1007/BF00200915" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1864609">Ketterling et al. (1991)</a> found that 6 (9%) had a C-to-T transition at base 31008 leading to the thr296-to-met mutation in the catalytic domain of factor IX. Five of the patients had the same haplotype and were known or presumed to be from the Amish group. All 6 patients had clinically mild disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1864609+2773937+5298508" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="0051" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0051 HEMOPHILIA B</strong>
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</h4>
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<div style="float: left;">
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F9, VAL307ALA
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852255 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852255;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=rs137852255" 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=rs137852255" 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=RCV000011354 OR RCV003764551 OR RCV004730842" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011354, RCV003764551, RCV004730842" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011354...</a>
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</span>
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<span class="mim-text-font">
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<p>See <a href="#23" class="mim-tip-reference" title="Bottema, C. D. K., Koeberl, D. D., Ketterling, R. P., Lillicrap, D. P., Bridges, P., Sommer, S. S. <strong>The molecular pathology of hemophilia B is a mirror of the pattern of recent germline mutations in humans. (Abstract)</strong> Blood 74: 252A, 1989."None>Bottema et al. (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically mild.</p>
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<br />
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<a id="0052" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0052 HEMOPHILIA B</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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F9, GLY309VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852256 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852256;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=rs137852256" 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=rs137852256" 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=RCV000011355" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011355" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011355</a>
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<span class="mim-text-font">
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<p>See <a href="#158" class="mim-tip-reference" title="Thompson, A. R., Chen, S.-H., Brayer, G. D. <strong>Severe hemophilia B due to a G to T transversion changing gly 309 to val and inhibiting active protease conformation by preventing ion pair formation. (Abstract)</strong> Blood 74: 134A, 1989."None>Thompson et al. (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically severe.</p>
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<a id="0053" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0053 HEMOPHILIA B</strong>
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<div>
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<div style="float: left;">
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F9, TRP310TER
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011356" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011356" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011356</a>
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</span>
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<span class="mim-text-font">
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<p>See <a href="#172" class="mim-tip-reference" title="Wang, N. S., Zhang, M., Thompson, A. R., Chen, S.-H. <strong>Factor IX(Chongqing): a new mutation in the calcium-binding domain of factor IX resulting in severe hemophilia B.</strong> Thromb. Haemost. 63: 24-26, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2339358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2339358</a>]" pmid="2339358">Wang et al. (1990)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically severe. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2339358" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="0054" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0054 HEMOPHILIA B</strong>
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F9, GLY311ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852257 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852257;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=rs137852257" 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=rs137852257" 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=RCV000011357 OR RCV000851648" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011357, RCV000851648" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011357...</a>
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</span>
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<span class="mim-text-font">
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<p>See <a href="#93" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Buerstedde, J.-M., Sommer, S. S. <strong>Functionally important regions of the factor IX gene have a low rate of polymorphism and a high rate of mutation in the dinucleotide CpG.</strong> Am. J. Hum. Genet. 45: 448-457, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2773937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2773937</a>]" pmid="2773937">Koeberl et al. (1989)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2773937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="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 B</strong>
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</h4>
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</div>
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<div>
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<div style="float: left;">
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F9, ARG333TER
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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> rs137852258 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852258;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/rs137852258?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=rs137852258" 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=rs137852258" 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=RCV000011358 OR RCV001000157 OR RCV001851791 OR RCV004791216" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011358, RCV001000157, RCV001851791, RCV004791216" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011358...</a>
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<p>See <a href="#182" class="mim-tip-reference" title="Zhang, M., Chen, S.-H., Thompson, A. R., Lovrien, E., Scott, C. R. <strong>CG dinucleotides are 'hot spots' in the factor IX gene for point mutations: evidence from the study of 25 families with defined mutations causing hemophilia B. (Abstract)</strong> Am. J. Hum. Genet. 45: A231, 1989."None>Zhang et al. (1989)</a>. This mutation, due to a transition at a CpG dinucleotide, was found by <a href="#94" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Ketterling, R. P., Bridge, P. J., Lillicrap, D. P., Sommer, S. S. <strong>Mutations causing hemophilia B: direct estimate of the underlying rates of spontaneous germ-line transitions, transversions, and deletions in a human gene.</strong> Am. J. Hum. Genet. 47: 202-217, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2198809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2198809</a>]" pmid="2198809">Koeberl et al. (1990)</a> in 2 patients with severe hemophilia B (<a href="/entry/306900">306900</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2198809" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0056 HEMOPHILIA B</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">rs137852259 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852259;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=rs137852259" 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=rs137852259" 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=RCV000011359 OR RCV000851995 OR RCV001000156 OR RCV001851792 OR RCV004799740" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011359, RCV000851995, RCV001000156, RCV001851792, RCV004799740" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011359...</a>
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<p><a href="#161" class="mim-tip-reference" title="Tsang, T. C., Bentley, D. R., Mibashan, R. S., Giannelli, F. <strong>A factor IX mutation, verified by direct genomic sequencing, causing haemophilia B by a novel mechanism.</strong> EMBO J. 7: 3009-3015, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3181127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3181127</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1988.tb03164.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3181127">Tsang et al. (1988)</a> characterized the mutation in factor IX London-2, which caused a severe CRM+ hemophilia B (<a href="/entry/306900">306900</a>). <a href="#161" class="mim-tip-reference" title="Tsang, T. C., Bentley, D. R., Mibashan, R. S., Giannelli, F. <strong>A factor IX mutation, verified by direct genomic sequencing, causing haemophilia B by a novel mechanism.</strong> EMBO J. 7: 3009-3015, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3181127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3181127</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1988.tb03164.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3181127">Tsang et al. (1988)</a> found a G-to-A transition at position 31119. The mutation resulted in substitution of glutamine for arginine at position 333. This arginine residue is conserved in the catalytic domain of normal human and bovine factor IX, factor X, and prothrombin. This mutation pinpoints a functionally critical feature of factor IX which may be involved in substrate or cofactor binding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3181127" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0057 HEMOPHILIA B</strong>
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F9, CYS336ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852260 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852260;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=rs137852260" 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=rs137852260" 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=RCV000011360 OR RCV003764552" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011360, RCV003764552" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011360...</a>
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<p>See <a href="#75" class="mim-tip-reference" title="Green, P. M., Bentley, D. R., Mibashan, R. S., Nilsson, I. M., Giannelli, F. <strong>Molecular pathology of haemophilia B.</strong> EMBO J. 8: 1067-1072, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2743975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2743975</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1989.tb03474.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2743975">Green et al. (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically of moderate severity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2743975" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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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<h4>
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<strong>.0058 HEMOPHILIA B</strong>
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F9, ARG338TER
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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> rs137852261 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852261;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/rs137852261?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=rs137852261" 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=rs137852261" 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=RCV000011361 OR RCV001000158 OR RCV001048961 OR RCV003398481" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011361, RCV001000158, RCV001048961, RCV003398481" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011361...</a>
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</span>
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<p><a href="#109" class="mim-tip-reference" title="Ludwig, M., Schwaab, R., Eigel, A., Horst, J., Egli, H., Brackmann, H.-H., Olek, K. <strong>Identification of a single nucleotide C-to-T transition and five different deletions in patients with severe hemophilia B.</strong> Am. J. Hum. Genet. 45: 115-122, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2741941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2741941</a>]" pmid="2741941">Ludwig et al. (1989)</a> demonstrated a C-to-T transition at amino acid 338, converting the CGA codon for arginine to a TGA stop codon. The variant was called factor IX Bonn-1. The hemophilia (<a href="/entry/306900">306900</a>) was clinically severe. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2741941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0059 REMOVED FROM DATABASE</strong>
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<strong>.0060 HEMOPHILIA B</strong>
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F9, MET348VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852262 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852262;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=rs137852262" 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=rs137852262" 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=RCV000011362" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011362" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011362</a>
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</span>
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<span class="mim-text-font">
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<p>Information was provided by <a href="#41" class="mim-tip-reference" title="Chen, S.-H., Thompson, A. R. <strong>Personal Communication.</strong> Seattle, Wash. 11/1989."None>Chen and Thompson (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically of moderate severity.</p>
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<strong>.0061 HEMOPHILIA B</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">rs137852263 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852263;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=rs137852263" 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=rs137852263" 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=RCV000011363" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011363" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011363</a>
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<span class="mim-text-font">
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<p>Information was provided by <a href="#41" class="mim-tip-reference" title="Chen, S.-H., Thompson, A. R. <strong>Personal Communication.</strong> Seattle, Wash. 11/1989."None>Chen and Thompson (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically of moderate severity.</p>
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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 B</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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F9, GLY363VAL
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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">rs387906479 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906479;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=rs387906479" 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=rs387906479" 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=RCV000011364" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011364" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011364</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>See <a href="#145" class="mim-tip-reference" title="Spitzer, S. G., Pendurthi, U. R., Kasper, C. K., Bajaj, S. P. <strong>Molecular defect in factor IX (Bm Lake Elsinore): substitution of ala390 by val in the catalytic domain.</strong> J. Biol. Chem. 263: 10545-10548, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3392024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3392024</a>]" pmid="3392024">Spitzer et al. (1988)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically of moderate severity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3392024" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="0063" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0063 HEMOPHILIA B</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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F9, GLY367ARG
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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=RCV000011365" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011365" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011365</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>Information was provided by <a href="#41" class="mim-tip-reference" title="Chen, S.-H., Thompson, A. R. <strong>Personal Communication.</strong> Seattle, Wash. 11/1989."None>Chen and Thompson (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically severe.</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="0064" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0064 HEMOPHILIA B</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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F9, PRO368THR
|
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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> rs137852265 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852265;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/rs137852265?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=rs137852265" 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=rs137852265" 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=RCV000011366" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011366" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011366</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>See Bertina et al. (<a href="#10" class="mim-tip-reference" title="Bertina, R. M., van der Linden, I. K., Mannucci, P. M., Reinalda-Poot, H. H., Cupers, R., Poort, S. R., Reitsma, P. H. <strong>Mutations in haemophilia B-M occur at the 180arg-to-val activation site or in the catalytic domain. (Abstract)</strong> Thromb. Haemost. 62: 203, 1989."None>1989</a>, <a href="#11" class="mim-tip-reference" title="Bertina, R. M., van der Linden, I. K., Mannucci, P. M., Reinalda-Poot, H. H., Cupers, R., Poort, S. R., Reitsma, P. H. <strong>Mutations in hemophilia B(m) occur at the arg(180)-to-val activation site or in the catalytic domain of factor IX.</strong> J. Biol. Chem. 265: 10876-10883, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2162822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2162822</a>]" pmid="2162822">1990</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2162822" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>
|
|
<a id="0065" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0065 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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<div style="float: left;">
|
|
F9, PHE378LEU
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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=RCV000011367" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011367" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011367</a>
|
|
</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>Information was provided by <a href="#41" class="mim-tip-reference" title="Chen, S.-H., Thompson, A. R. <strong>Personal Communication.</strong> Seattle, Wash. 11/1989."None>Chen and Thompson (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically severe.</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>
|
|
<a id="0066" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0066 HEMOPHILIA B</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
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|
|
|
<div style="float: left;">
|
|
F9, ALA390GLU
|
|
</div>
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|
</span>
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|
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|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852266 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852266;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=rs137852266" 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=rs137852266" 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=RCV000011368" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011368" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011368</a>
|
|
</span>
|
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|
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|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>Information was provided by <a href="#160" class="mim-tip-reference" title="Thompson, A. R. <strong>Personal Communication.</strong> Seattle, Wash. 11/1989."None>Thompson (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically of moderate severity.</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>
|
|
<a id="0067" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0067 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
F9, ALA390VAL
|
|
</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">rs137852266 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852266;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=rs137852266" 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=rs137852266" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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|
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|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011369" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011369" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011369</a>
|
|
</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p><a href="#145" class="mim-tip-reference" title="Spitzer, S. G., Pendurthi, U. R., Kasper, C. K., Bajaj, S. P. <strong>Molecular defect in factor IX (Bm Lake Elsinore): substitution of ala390 by val in the catalytic domain.</strong> J. Biol. Chem. 263: 10545-10548, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3392024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3392024</a>]" pmid="3392024">Spitzer et al. (1988)</a> found substitution of valine for alanine at position 390, resulting from a single base substitution (C-to-T) in exon 8. <a href="#151" class="mim-tip-reference" title="Sugimoto, M., Miyata, T., Kawabata, S., Yoshioka, A., Fukui, H., Takahashi, H., Iwanaga, S. <strong>Blood clotting factor IX Niigata: substitution of alanine-390 by valine in the catalytic domain.</strong> J. Biochem. 104: 878-880, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3243764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3243764</a>] [<a href="https://doi.org/10.1093/oxfordjournals.jbchem.a122575" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3243764">Sugimoto et al. (1988)</a> demonstrated substitution of valine for alanine at position 390 in the catalytic domain as the molecular defect in factor IX Niigata. The patient had a moderately severe form of hemophilia B (<a href="/entry/306900">306900</a>) with a normal level of factor IX antigen but very low clotting activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3392024+3243764" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#11" class="mim-tip-reference" title="Bertina, R. M., van der Linden, I. K., Mannucci, P. M., Reinalda-Poot, H. H., Cupers, R., Poort, S. R., Reitsma, P. H. <strong>Mutations in hemophilia B(m) occur at the arg(180)-to-val activation site or in the catalytic domain of factor IX.</strong> J. Biol. Chem. 265: 10876-10883, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2162822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2162822</a>]" pmid="2162822">Bertina et al. (1990)</a> referred to this mutation as factor IX Lake Elsinore. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2162822" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="0068" class="mim-anchor"></a>
|
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<h4>
|
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<span class="mim-font">
|
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<strong>.0068 HEMOPHILIA B</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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F9, GLY396ARG
|
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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">rs137852267 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852267;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=rs137852267" 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=rs137852267" 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=RCV000011370" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011370" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011370</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="#6" class="mim-tip-reference" title="Attree, O., Vidaud, M., Vidaud, D., Lavergne, J. M., Goossens, M. <strong>New strategies for rapid detection and characterization of mutations in hemophilia B. (Abstract)</strong> Thromb. Haemost. 62: 8, 1989."None>Attree et al. (1989)</a> designed a strategy allowing rapid analysis of the critical serine protease catalytic domain of activated factor IX, encoded by exons 7 and 8 of the gene. The method involved enzymatic amplification of genomic DNA, analysis of the amplification products by denaturing gradient gel electrophoresis, and direct sequencing of the fragments displaying an altered melting behavior. They used this procedure to characterize 2 'new' mutations in hemophilia B (<a href="/entry/306900">306900</a>): factor IX Angers, a G-to-A substitution generating an arg in place of a gly at amino acid 396 of the mature factor IX protein; and factor IX Bordeaux, an A-to-T substitution introducing a nonsense codon in place of the normal codon for lys at position 411 (<a href="#0071">300746.0071</a>). The hemophilia was clinically severe.</p>
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<strong>.0069 HEMOPHILIA B</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">rs137852268 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852268;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=rs137852268" 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=rs137852268" 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=RCV000011371 OR RCV001382695 OR RCV001810850 OR RCV005042032" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011371, RCV001382695, RCV001810850, RCV005042032" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011371...</a>
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<p><a href="#173" class="mim-tip-reference" title="Ware, J., Davis, L., Frazier, D., Bajaj, S. P., Stafford, D. W. <strong>Genetic defect responsible for the dysfunctional protein: factor IX (Long Beach).</strong> Blood 72: 820-822, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3401602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3401602</a>]" pmid="3401602">Ware et al. (1988)</a> demonstrated that the defect in factor IX(Long Beach) is a result of a thymine-to-cytosine transition leading to the substitution of a threonine codon (ACA) for an isoleucine codon (ATA) in exon 8 of the F9 gene. In a case of hemophilia B (<a href="/entry/306900">306900</a>) of moderate severity, <a href="#63" class="mim-tip-reference" title="Geddes, V. A., Le Bonniec, B. F., Louie, G. V., Brayer, G. D., Thompson, A. R., MacGillivray, R. T. A. <strong>A moderate form of hemophilia B is caused by a novel mutation in the protease domain of factor IX(Vancouver).</strong> J. Biol. Chem. 264: 4689-4697, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2494175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2494175</a>]" pmid="2494175">Geddes et al. (1989)</a> found a mutation in the protease domain of factor IX that changed the codon for isoleucine-397 (ATA) to a threonine codon (ACA). The resulting abnormal protein had been named factor IX(Vancouver) (<a href="#64" class="mim-tip-reference" title="Geddes, V. A., Louie, G. V., Brayer, G. D., MacGillivray, R. T. A. <strong>Molecular basis of hemophilia B: identification of the defect in factor IX Vancouver. (Abstract)</strong> Thromb. Haemost. 58 (suppl.): 294, 1987."None>Geddes et al., 1987</a>). Thus, factor IX Long Beach, factor IX Vancouver, and factor IX Los Angeles have the same defect. In 11 of 65 consecutive males with hemophilia B (17%), <a href="#21" class="mim-tip-reference" title="Bottema, C. D. K., Ketterling, R. P., Yoon, H.-S., Sommer, S. S. <strong>The pattern of factor IX germ-line mutation in Asians is similar to that of Caucasians.</strong> Am. J. Hum. Genet. 47: 835-841, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2220823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2220823</a>]" pmid="2220823">Bottema et al. (1990)</a> found this mutation, a T-to-C transition at base 31311, which substitutes threonine for isoleucine-397. The 11 patients were of western European descent and had the same haplotype. Judging from the frequency of this haplotype, the probability of the same mutation occurring independently 11 times in this haplotype was considered to be minuscule. Despite the lack of overlapping pedigrees, a common ancestor for these patients was suspected. The clinical symptoms were considerably moderate/mild. <a href="#137" class="mim-tip-reference" title="Sarkar, G., Cassady, J. D., Pyeritz, R. E., Gilchrist, G. S., Sommer, S. S. <strong>Isoleucine-397 is changed to threonine in two females with hemophilia B.</strong> Nucleic Acids Res. 19: 1165, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1902289/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1902289</a>] [<a href="https://doi.org/10.1093/nar/19.5.1165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1902289">Sarkar et al. (1991)</a> found this mutation in 2 females with hemophilia B. Both were heterozygous, coming from unrelated families. Nonrandom X inactivation was proposed, although other possibilities included a second undetected intronic or promoter mutation. <a href="#43" class="mim-tip-reference" title="Chen, S.-H., Zhang, M., Lovrien, E. W., Scott, C. R., Thompson, A. R. <strong>CG dinucleotide transitions in the factor IX gene account for about half of the point mutations in hemophilia B patients: a Seattle series.</strong> Hum. Genet. 87: 177-182, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2066105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2066105</a>] [<a href="https://doi.org/10.1007/BF00204177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2066105">Chen et al. (1991)</a> found this mutation in 7 families which all shared a rare haplotype, suggesting a common ancestor. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2220823+2494175+3401602+1902289+2066105" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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">rs137852269 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852269;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=rs137852269" 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=rs137852269" 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=RCV000011372" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011372" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011372</a>
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<p>See <a href="#93" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Buerstedde, J.-M., Sommer, S. S. <strong>Functionally important regions of the factor IX gene have a low rate of polymorphism and a high rate of mutation in the dinucleotide CpG.</strong> Am. J. Hum. Genet. 45: 448-457, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2773937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2773937</a>]" pmid="2773937">Koeberl et al. (1989)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2773937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 B</strong>
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F9, LYS411TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852270 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852270;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=rs137852270" 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=rs137852270" 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=RCV000011373" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011373" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011373</a>
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<p>This variant has been designated factor IX Bordeaux. See <a href="#5" class="mim-tip-reference" title="Attree, O., Vidaud, D., Vidaud, M., Amselem, S., Lavergne, J.-M., Goossens, M. <strong>Mutations in the catalytic domain of human coagulation factor IX: rapid characterization by direct genomic sequencing of DNA fragments displaying an altered melting behavior.</strong> Genomics 4: 266-272, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2714791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2714791</a>] [<a href="https://doi.org/10.1016/0888-7543(89)90330-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2714791">Attree et al. (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically severe. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2714791" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 B</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011374" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011374" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011374</a>
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<p>Deletions of various sizes deleting exons 1-8 were reported by <a href="#67" class="mim-tip-reference" title="Giannelli, F., Choo, K. H., Rees, D. J. G., Boyd, Y., Rizza, C. R., Brownlee, G. G. <strong>Gene deletions in patients with haemophilia B and anti-factor IX antibodies.</strong> Nature 303: 181-182, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6843667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6843667</a>] [<a href="https://doi.org/10.1038/303181a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6843667">Giannelli et al. (1983)</a>, <a href="#3" class="mim-tip-reference" title="Anson, D. S., Blake, D. J., Winship, P. R., Birnbaum, D., Brownlee, G. G. <strong>Nullisomic deletion of the mcf.2 transforming gene in two haemophilia B patients.</strong> EMBO J. 7: 2795-2799, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2846283/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2846283</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1988.tb03134.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2846283">Anson et al. (1988)</a>, <a href="#157" class="mim-tip-reference" title="Taylor, S. A. M., Lillicrap, D. P., Blanchette, V., Giles, A. R., Holden, J. J. A., White, B. N. <strong>A complete deletion of the factor IX gene and new TaqI variant in a hemophilia B kindred.</strong> Hum. Genet. 79: 273-276, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2841226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2841226</a>] [<a href="https://doi.org/10.1007/BF00366250" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2841226">Taylor et al. (1988)</a>, <a href="#113" class="mim-tip-reference" title="Matthews, R. J., Anson, D. S., Peake, I. R., Bloom, A. L. <strong>Heterogeneity of the factor IX locus in nine hemophilia B inhibitor patients.</strong> J. Clin. Invest. 79: 746-753, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3029178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3029178</a>] [<a href="https://doi.org/10.1172/JCI112880" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3029178">Matthews et al. (1987)</a>, <a href="#109" class="mim-tip-reference" title="Ludwig, M., Schwaab, R., Eigel, A., Horst, J., Egli, H., Brackmann, H.-H., Olek, K. <strong>Identification of a single nucleotide C-to-T transition and five different deletions in patients with severe hemophilia B.</strong> Am. J. Hum. Genet. 45: 115-122, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2741941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2741941</a>]" pmid="2741941">Ludwig et al. (1989)</a>, <a href="#169" class="mim-tip-reference" title="Wadelius, C., Blomback, M., Pettersson, U. <strong>Molecular studies of haemophilia B in Sweden: identification of patients with total deletion of the factor IX gene and without inhibitory antibodies.</strong> Hum. Genet. 81: 13-17, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2848757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2848757</a>] [<a href="https://doi.org/10.1007/BF00283721" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2848757">Wadelius et al. (1988)</a>, <a href="#8" class="mim-tip-reference" title="Bernardi, F., Del Senno, L., Barbieri, R., Buzzoni, D., Gambari, R., Marchetti, G., Conconi, F., Panicucci, F., Positano, M., Pitruzzello, S. <strong>Gene deletion in an Italian haemophilia B subject.</strong> J. Med. Genet. 22: 305-307, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4045960/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4045960</a>] [<a href="https://doi.org/10.1136/jmg.22.4.305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4045960">Bernardi et al. (1985)</a>, <a href="#117" class="mim-tip-reference" title="Mikami, S., Nishino, M., Nishimura, T., Fukui, H. <strong>RFLPs of factor IX gene in Japanese haemophilia B families and gene deletion in two high-responder-inhibitor patients.</strong> Jpn. J. Hum. Genet. 32: 21-31, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2886685/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2886685</a>] [<a href="https://doi.org/10.1007/BF01876524" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2886685">Mikami et al. (1987)</a>, <a href="#152" class="mim-tip-reference" title="Tanimoto, M., Kojima, T., Kamiya, T., Takamatsu, J., Ogata, K., Obata, Y., Inagaki, M., Iizuka, A., Nagao, T., Kurachi, K., Saito, H. <strong>DNA analysis of seven patients with hemophilia B who have anti-factor IX antibodies: relationship to clinical manifestations and evidence that the abnormal gene was inherited.</strong> J. Lab. Clin. Med. 112: 307-313, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3411192/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3411192</a>]" pmid="3411192">Tanimoto et al. (1988)</a>, <a href="#93" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Buerstedde, J.-M., Sommer, S. S. <strong>Functionally important regions of the factor IX gene have a low rate of polymorphism and a high rate of mutation in the dinucleotide CpG.</strong> Am. J. Hum. Genet. 45: 448-457, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2773937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2773937</a>]" pmid="2773937">Koeberl et al. (1989)</a>, and <a href="#81" class="mim-tip-reference" title="Hassan, H. J., Leonardi, A., Guerriero, R., Chelucci, C., Cianetti, L., Ciavarella, N., Ranieri, P., Pilolli, D., Peschle, C. <strong>Hemophilia B with inhibitor: molecular analysis of the subtotal deletion of the factor IX gene.</strong> Blood 66: 728-730, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2992643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2992643</a>]" pmid="2992643">Hassan et al. (1985)</a>. Some of the deletions were associated with development of inhibitors and others of comparable size were not. The hemophilia (<a href="/entry/306900">306900</a>) was clinically severe. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2841226+6843667+4045960+2992643+2886685+2773937+3029178+2848757+2741941+2846283+3411192" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0073 HEMOPHILIA B</strong>
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F9, EX1DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011375" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011375" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011375</a>
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<p><a href="#109" class="mim-tip-reference" title="Ludwig, M., Schwaab, R., Eigel, A., Horst, J., Egli, H., Brackmann, H.-H., Olek, K. <strong>Identification of a single nucleotide C-to-T transition and five different deletions in patients with severe hemophilia B.</strong> Am. J. Hum. Genet. 45: 115-122, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2741941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2741941</a>]" pmid="2741941">Ludwig et al. (1989)</a> described deletion of exon 1 in a case of severe hemophilia B (<a href="/entry/306900">306900</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2741941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0074 HEMOPHILIA B</strong>
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F9, EX1-3DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011376" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011376" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011376</a>
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<p>See <a href="#109" class="mim-tip-reference" title="Ludwig, M., Schwaab, R., Eigel, A., Horst, J., Egli, H., Brackmann, H.-H., Olek, K. <strong>Identification of a single nucleotide C-to-T transition and five different deletions in patients with severe hemophilia B.</strong> Am. J. Hum. Genet. 45: 115-122, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2741941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2741941</a>]" pmid="2741941">Ludwig et al. (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was severe and was associated with serum inhibitors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2741941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0075 HEMOPHILIA B</strong>
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F9, EX2-8DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011377" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011377" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011377</a>
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<p>Information was provided by <a href="#41" class="mim-tip-reference" title="Chen, S.-H., Thompson, A. R. <strong>Personal Communication.</strong> Seattle, Wash. 11/1989."None>Chen and Thompson (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was severe and was associated with serum inhibitors.</p>
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<a id="0076" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0076 HEMOPHILIA B</strong>
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F9, EX4-5DEL
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011378" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011378" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011378</a>
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<p>See <a href="#109" class="mim-tip-reference" title="Ludwig, M., Schwaab, R., Eigel, A., Horst, J., Egli, H., Brackmann, H.-H., Olek, K. <strong>Identification of a single nucleotide C-to-T transition and five different deletions in patients with severe hemophilia B.</strong> Am. J. Hum. Genet. 45: 115-122, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2741941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2741941</a>]" pmid="2741941">Ludwig et al. (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically severe. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2741941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="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 B</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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F9, EX4DEL
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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=RCV000011379" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011379" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011379</a>
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</span>
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<p>See <a href="#166" class="mim-tip-reference" title="Vidaud, M., Chabret, C., Gazengel, C., Grunebaum, L., Cazenave, J. P., Goossens, M. <strong>A de novo intragenic deletion of the potential EGF domain of the factor IX gene in a family with severe hemophilia B.</strong> Blood 68: 961-963, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2875754/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2875754</a>]" pmid="2875754">Vidaud et al. (1986)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically severe. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2875754" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="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 B</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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F9, EX4INS
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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=RCV000011380" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011380" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011380</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 moderate to severe hemophilia B (<a href="/entry/306900">306900</a>), <a href="#38" class="mim-tip-reference" title="Chen, S.-H., Scott, C. R., Edson, J. R., Kurachi, K. <strong>An insertion within the factor IX gene: hemophilia B(El Salvador).</strong> Am. J. Hum. Genet. 42: 581-584, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2831715/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2831715</a>]" pmid="2831715">Chen et al. (1988)</a> found a large insertion in the F9 gene, which appeared to have originated from outside the gene rather than to represent an internal duplication. The variant was called factor IX El Salvador for the birthplace of the patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2831715" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="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 B</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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F9, EX5-8DEL
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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=RCV000011381" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011381" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011381</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>See <a href="#113" class="mim-tip-reference" title="Matthews, R. J., Anson, D. S., Peake, I. R., Bloom, A. L. <strong>Heterogeneity of the factor IX locus in nine hemophilia B inhibitor patients.</strong> J. Clin. Invest. 79: 746-753, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3029178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3029178</a>] [<a href="https://doi.org/10.1172/JCI112880" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3029178">Matthews et al. (1987)</a> and <a href="#124" class="mim-tip-reference" title="Peake, I. R., Matthews, R. J., Bloom, A. L. <strong>Haemophilia B Chicago: severe haemophilia B caused by two deletions and an inversion within the factor IX gene.</strong> Brit. J. Haemat. 71 (suppl. 1): 1, 1989."None>Peake et al. (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was severe and was associated with serum inhibitors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3029178" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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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<div>
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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 MOVED TO <a href="/entry/300746#0098">300746.0098</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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</div>
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</div>
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<div>
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<div>
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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 B</strong>
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F9, EX7DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011383" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011383" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011383</a>
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<p>See <a href="#109" class="mim-tip-reference" title="Ludwig, M., Schwaab, R., Eigel, A., Horst, J., Egli, H., Brackmann, H.-H., Olek, K. <strong>Identification of a single nucleotide C-to-T transition and five different deletions in patients with severe hemophilia B.</strong> Am. J. Hum. Genet. 45: 115-122, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2741941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2741941</a>]" pmid="2741941">Ludwig et al. (1989)</a>. The hemophilia (<a href="/entry/306900">306900</a>) was clinically severe. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2741941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0082 HEMOPHILIA B</strong>
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F9, 1-BP DEL, ASP85FS
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011384" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011384" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011384</a>
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<p>This variant has been designated factor IX Seattle-2.</p><p>In a case of severe hemophilia B (<a href="/entry/306900">306900</a>), <a href="#138" class="mim-tip-reference" title="Schach, B. G., Yoshitake, S., Davie, E. W. <strong>Hemophilia B (factor IX-Seattle 2) due to a single nucleotide deletion in the gene for factor IX.</strong> J. Clin. Invest. 80: 1023-1028, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2821070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2821070</a>] [<a href="https://doi.org/10.1172/JCI113155" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2821070">Schach et al. (1987)</a> found deletion of a single adenine nucleotide in exon 5. This resulted in a frameshift that converted an aspartic acid at position 85 in the protein to a valine and the formation of a stop signal at position 86. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2821070" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="0083" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0083 HEMOPHILIA B</strong>
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F9, VAL328PHE
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852271 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852271;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=rs137852271" 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=rs137852271" 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=RCV000011385 OR RCV001001418" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011385, RCV001001418" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011385...</a>
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</span>
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<span class="mim-text-font">
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<p><a href="#180" class="mim-tip-reference" title="Winship, P. R. <strong>Haemophilia B caused by mutation of a potential thrombin cleavage site in factor IX.</strong> Nucleic Acids Res. 18: 1310, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2320433/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2320433</a>] [<a href="https://doi.org/10.1093/nar/18.5.1310" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2320433">Winship (1990)</a> found a substitution of valine by phenylalanine at residue 328 in exon h of factor IX in a patient with hemophilia B (<a href="/entry/306900">306900</a>) referred to as hemophilia B Oxford h5 (Oxh5). The substitution was caused by a G-to-T transversion at nucleotide 31103. Arg327-val328 is the major thrombin cleavage site in factor IX. <a href="#180" class="mim-tip-reference" title="Winship, P. R. <strong>Haemophilia B caused by mutation of a potential thrombin cleavage site in factor IX.</strong> Nucleic Acids Res. 18: 1310, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2320433/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2320433</a>] [<a href="https://doi.org/10.1093/nar/18.5.1310" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2320433">Winship (1990)</a> suggested that the mutant protein may have increased susceptibility to thrombin cleavage with resulting in vivo instability of the mutant protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2320433" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="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 B</strong>
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F9, ARG116TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852272 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852272;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=rs137852272" 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=rs137852272" 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=RCV000011386 OR RCV001000188 OR RCV003764553" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011386, RCV001000188, RCV003764553" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011386...</a>
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<p>In a 4-year-old boy with severe hemophilia B (<a href="/entry/306900">306900</a>), an isolated case in his family, <a href="#119" class="mim-tip-reference" title="Montandon, A. J., Green, P. M., Bentley, D. R., Ljung, R., Nilsson, I. M., Giannelli, F. <strong>Two factor IX mutations in the family of an isolated haemophilia B patient: direct carrier diagnosis by amplification mismatch detection (AMD).</strong> Hum. Genet. 85: 200-204, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2370049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2370049</a>] [<a href="https://doi.org/10.1007/BF00193196" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2370049">Montandon et al. (1990)</a> identified a C-to-T transition at residue 17762 resulting in a translation stop at codon arginine-116. A second mutation in this patient at residue 30890 resulted in a his257-to-tyr substitution (<a href="#0085">300746.0085</a>); this mutation was subsequently shown to be neutral by the fact that its origin preceded the maternal grandfather and it produced no reduction in factor IX coagulant and antigen level in the grandfather. On the other hand, analysis of other family members showed that the mutation for arg116-to-ter had occurred at gametogenesis in the paternal grandfather. The patient was referred to as Malmo 7. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2370049" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="0085" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong><div class="mim-changed mim-change">.0085 F9 POLYMORPHISM</div></strong>
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F9, HIS257TYR
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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> rs1801202 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1801202;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/rs1801202?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=rs1801202" 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=rs1801202" 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=RCV000011387 OR RCV001081157 OR RCV001167683 OR RCV002496326 OR RCV003944813" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011387, RCV001081157, RCV001167683, RCV002496326, RCV003944813" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011387...</a>
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<span class="mim-text-font">
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<p>See <a href="#0084">300746.0084</a>.</p>
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<a id="0086" class="mim-anchor"></a>
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<strong>.0086 HEMOPHILIA B</strong>
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F9, CYS350SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852273 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852273;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=rs137852273" 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=rs137852273" 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=RCV000011388" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011388" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011388</a>
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<p><a href="#153" class="mim-tip-reference" title="Taylor, S. A. M., Deugau, K. V., Lillicrap, D. P. <strong>Somatic mosaicism and female-to-female transmission in a kindred with hemophilia B (factor IX deficiency).</strong> Proc. Nat. Acad. Sci. 88: 39-42, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1986380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1986380</a>] [<a href="https://doi.org/10.1073/pnas.88.1.39" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1986380">Taylor et al. (1991)</a> described a male patient with hemophilia B (<a href="/entry/306900">306900</a>) in whom they documented somatic mosaicism for a cysteine-to-serine alteration at codon 350 in the catalytic domain of factor IX. The mutation resulted from a G-to-C transversion at nucleotide 31170. Using a combination of allele-specific oligonucleotide hybridization and differential termination of primer extension, <a href="#153" class="mim-tip-reference" title="Taylor, S. A. M., Deugau, K. V., Lillicrap, D. P. <strong>Somatic mosaicism and female-to-female transmission in a kindred with hemophilia B (factor IX deficiency).</strong> Proc. Nat. Acad. Sci. 88: 39-42, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1986380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1986380</a>] [<a href="https://doi.org/10.1073/pnas.88.1.39" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1986380">Taylor et al. (1991)</a> showed that hepatic, renal, smooth muscle, and hematopoietic cells possessed both normal and mutant factor IX sequences. An additional unusual phenomenon in this pedigree was the presence of 2 females in successive generations with moderately severe factor IX deficiency. These females were the daughter and granddaughter of the proband. No evidence of X chromosome or autosome cytogenetic abnormalities was found, no additional sequence alterations were identified in the factor IX gene in either woman and no gross changes were observed on Southern analysis of the regulatory regions in the 5-prime and 3-prime ends of the gene. The normal X chromosomes of the 2 women were shown to have different haplotypes at the factor IX locus. <a href="#153" class="mim-tip-reference" title="Taylor, S. A. M., Deugau, K. V., Lillicrap, D. P. <strong>Somatic mosaicism and female-to-female transmission in a kindred with hemophilia B (factor IX deficiency).</strong> Proc. Nat. Acad. Sci. 88: 39-42, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1986380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1986380</a>] [<a href="https://doi.org/10.1073/pnas.88.1.39" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1986380">Taylor et al. (1991)</a> speculated that the X chromosome bearing the normal factor IX gene has been exclusively inactivated in both affected women, possibly secondary to a second genetic change affecting the primary inactivation center on the mutant X chromosome and resulting in a failure of inactivation of the mutant factor IX sequences. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1986380" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 B</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">rs137852274 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852274;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=rs137852274" 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=rs137852274" 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=RCV000011389" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011389" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011389</a>
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<p><a href="#177" class="mim-tip-reference" title="Winship, P. R., Dragon, A. C. <strong>Identification of haemophilia B patients with mutations in the two calcium binding domains of factor IX: importance of a beta-OH asp64-to-asn change.</strong> Brit. J. Haemat. 77: 102-109, 1991. Note: Erratum: Brit. J. Haemat. 77: 446 only, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1998585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1998585</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1991.tb07955.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1998585">Winship and Dragon (1991)</a> described a G-to-A transition at nucleotide 10442 of the F9 gene, resulting in substitution of asparagine for aspartic acid-64 (D64N). The change resulted in a functionally defective factor IX molecule that altered calcium-binding properties. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1998585" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0088 HEMOPHILIA B LEYDEN</strong>
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F9, +8T-C
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2148352869 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2148352869;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=rs2148352869" 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=rs2148352869" 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=RCV000011390" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011390" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011390</a>
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<p>In an Anglo-Irish family living in New Zealand, <a href="#134" class="mim-tip-reference" title="Royle, G., Van de Water, N. S., Berry, E., Ockelford, P. A., Browett, P. J. <strong>Haemophilia B Leyden arising de novo by point mutation in the putative factor IX promoter region.</strong> Brit. J. Haemat. 77: 191-194, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2004020/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2004020</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1991.tb07976.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2004020">Royle et al. (1991)</a> identified a T-to-C transition at position +8 in the promoter region of the F9 gene as the cause of hemophilia B Leyden (see <a href="/entry/306900">306900</a>). This mutation is situated within the repeat consensus sequence in the transcribed but untranslated portion of the gene. The mutation had arisen de novo in the proband. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2004020" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0089 HEMOPHILIA B LEYDEN</strong>
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F9, -5A-T, PROMOTER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1927322453 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1927322453;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=rs1927322453" 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=rs1927322453" 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=RCV000011391" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011391" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011391</a>
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<p>In a 3-year-old boy with hemophilia B Leyden (<a href="/entry/306900">306900</a>), <a href="#126" class="mim-tip-reference" title="Picketts, D. J., D'Souza, C., Bridge, P. J., Lillicrap, D. <strong>An A to T transversion at position -5 of the factor IX promoter results in hemophilia B.</strong> Genomics 12: 161-163, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1733855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1733855</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90421-n" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1733855">Picketts et al. (1992)</a> described an A-to-T transversion at position -5 of the factor IX promoter. <a href="#127" class="mim-tip-reference" title="Picketts, D. J., Lillicrap, D. P., Mueller, C. R. <strong>Synergy between transcription factors DBP and C/EBP compensates for a haemophilia B Leyden factor IX mutation.</strong> Nature Genet. 3: 175-179, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8499951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8499951</a>] [<a href="https://doi.org/10.1038/ng0293-175" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8499951">Picketts et al. (1993)</a> identified 5 transcription factor binding sites within the F9 promoter and showed that the Leyden mutation at nucleotide -5 interfered with the binding of proteins to 1 of 3 newly identified sites. The correlation between the postpubertal recovery of these mutants and the induction of the transcription factor DBP (D-site binding protein; <a href="/entry/124097">124097</a>) led <a href="#127" class="mim-tip-reference" title="Picketts, D. J., Lillicrap, D. P., Mueller, C. R. <strong>Synergy between transcription factors DBP and C/EBP compensates for a haemophilia B Leyden factor IX mutation.</strong> Nature Genet. 3: 175-179, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8499951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8499951</a>] [<a href="https://doi.org/10.1038/ng0293-175" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8499951">Picketts et al. (1993)</a> to the discovery of a synergistic interaction between DBP and C/EBP (CCAAT/enhancer binding protein; <a href="/entry/116897">116897</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1733855+8499951" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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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<strong>.0090 HEMOPHILIA B LEYDEN</strong>
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F9, +13A-G
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1927322926 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1927322926;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=rs1927322926" 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=rs1927322926" 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=RCV000011392 OR RCV003764554 OR RCV004791217" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011392, RCV003764554, RCV004791217" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011392...</a>
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<p>As indicated in <a href="#0004">300746.0004</a>, <a href="#132" class="mim-tip-reference" title="Reitsma, P. H., Mandalaki, T., Kasper, C. K., Bertina, R. M., Briet, E. <strong>Two novel point mutations correlate with an altered developmental expression of blood coagulation factor IX (hemophilia B Leyden phenotype).</strong> Blood 73: 743-746, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2917196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2917196</a>]" pmid="2917196">Reitsma et al. (1989)</a> found an A-to-G mutation at position +13 of the factor IX gene in an American patient of Armenian descent with hemophilia B Leyden (see <a href="/entry/306900">306900</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2917196" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="0091" class="mim-anchor"></a>
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<strong>.0091 HEMOPHILIA B</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">rs137852275 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852275;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=rs137852275" 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=rs137852275" 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=RCV000011393 OR RCV001810851" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011393, RCV001810851" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011393...</a>
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<p>In a patient with hemophilia B (<a href="/entry/306900">306900</a>), <a href="#118" class="mim-tip-reference" title="Miyata, T., Sakai, T., Sugimoto, M., Naka, H., Yamamoto, K., Yoshioka, A., Fukui, H., Mitsui, K., Kamiya, K., Umeyama, H., Iwanaga, S. <strong>Factor IX Amagasaki: a new mutation in the catalytic domain resulting in the loss of both coagulant and esterase activities.</strong> Biochemistry 30: 11286-11291, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1958666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1958666</a>] [<a href="https://doi.org/10.1021/bi00111a014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1958666">Miyata et al. (1991)</a> identified a G-to-A substitution in exon 8 resulting in replacement of glycine-311, a highly conserved amino acid residue among serine proteases, by glutamic acid. The mutation resulted in complete loss of both coagulant activity and esterase activity. The variant was designated factor IX Amagasaki. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1958666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 B</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011394" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011394" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011394</a>
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<p>In a 17-year-old male with severe hemophilia B (<a href="/entry/306900">306900</a>), <a href="#142" class="mim-tip-reference" title="Solera, J., Magallon, M., Martin-Villar, J., Coloma, A. <strong>Factor IX(Madrid 2): a deletion/insertion in factor IX gene which abolishes the sequence of the donor junction at the exon IV-intron d splice site.</strong> Am. J. Hum. Genet. 50: 434-437, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1346483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1346483</a>]" pmid="1346483">Solera et al. (1992)</a> found a 4,442-bp deletion, which removed both the donor splice site located at the 5-prime end of intron d and the last 2 coding nucleotides located at the 3-prime end of exon 4. This fragment had been replaced by a 47-bp sequence from the normal factor IX gene, inserted in inverted orientation. They identified 2 homologous sequences at the ends of the deleted DNA fragment. The variant was designated factor IX Madrid-2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1346483" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0093 HEMOPHILIA B</strong>
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F9, SER365ILE
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852276 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852276;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=rs137852276" 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=rs137852276" 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=RCV000011395" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011395" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011395</a>
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<p><a href="#108" class="mim-tip-reference" title="Ludwig, M., Sabharwal, A. K., Brackmann, H. H., Olek, K., Smith, K. J., Birktoft, J. J., Bajaj, S. P. <strong>Hemophilia B caused by five different nondeletion mutations in the protease domain of factor IX.</strong> Blood 79: 1225-1232, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1346975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1346975</a>]" pmid="1346975">Ludwig et al. (1992)</a> described the molecular basis of hemophilia B (<a href="/entry/306900">306900</a>) in 5 patients who had neither deletions nor rearrangements of the F9 gene. By enzymatic amplification and sequencing of all exons and promoter regions, a causative mutation in the protease domain was identified in each patient. The first was a G-to-T transversion at nucleotide 31215, leading to substitution of isoleucine for serine-365. The variant was designated factor IX Schmallenberg. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1346975" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 B</strong>
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F9, SER365GLY
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852277 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852277;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=rs137852277" 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=rs137852277" 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=RCV000011396 OR RCV002512972" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011396, RCV002512972" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011396...</a>
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<p>In a patient with hemophilia B (<a href="/entry/306900">306900</a>), <a href="#108" class="mim-tip-reference" title="Ludwig, M., Sabharwal, A. K., Brackmann, H. H., Olek, K., Smith, K. J., Birktoft, J. J., Bajaj, S. P. <strong>Hemophilia B caused by five different nondeletion mutations in the protease domain of factor IX.</strong> Blood 79: 1225-1232, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1346975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1346975</a>]" pmid="1346975">Ludwig et al. (1992)</a> demonstrated an A-to-G transition at nucleotide 31214 resulting in replacement of serine-365 by glycine. The variant was designated factor IX Varel. The mutation occurs at the same codon as that involved in factor IX Schmallenberg (<a href="#0093">300746.0093</a>). This patient also had a silent mutation (GAT to GAC) at asp364. Thus, this patient had a double basepair substitution of TA to CG at nucleotides 31213 and 31214 but only a single amino acid change of ser365-to-gly. This patient also developed an antibody to factor IX during replacement therapy, which suggested that deletion of the factor IX gene is not necessary for development of antibody. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1346975" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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F9, ASP364HIS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852278 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852278;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=rs137852278" 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=rs137852278" 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=RCV000011397" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011397" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011397</a>
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<p>In a patient with hemophilia B (<a href="/entry/306900">306900</a>), <a href="#108" class="mim-tip-reference" title="Ludwig, M., Sabharwal, A. K., Brackmann, H. H., Olek, K., Smith, K. J., Birktoft, J. J., Bajaj, S. P. <strong>Hemophilia B caused by five different nondeletion mutations in the protease domain of factor IX.</strong> Blood 79: 1225-1232, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1346975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1346975</a>]" pmid="1346975">Ludwig et al. (1992)</a> identified a G-to-C transversion at nucleotide 31211, resulting in substitution of his for asp364. The variant was designated factor IX Mechtal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1346975" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 B</strong>
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F9, GLU245VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852279 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852279;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=rs137852279" 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=rs137852279" 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=RCV000011398" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011398" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011398</a>
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<p>In a patient with hemophilia B (<a href="/entry/306900">306900</a>), <a href="#108" class="mim-tip-reference" title="Ludwig, M., Sabharwal, A. K., Brackmann, H. H., Olek, K., Smith, K. J., Birktoft, J. J., Bajaj, S. P. <strong>Hemophilia B caused by five different nondeletion mutations in the protease domain of factor IX.</strong> Blood 79: 1225-1232, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1346975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1346975</a>]" pmid="1346975">Ludwig et al. (1992)</a> identified an A-to-T transversion at nucleotide 30855, resulting in substitution of valine for glutamic acid-245. The variant was designated factor IX Monschau. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1346975" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0097 HEMOPHILIA B BRANDENBURG</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">rs2148352851 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2148352851;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=rs2148352851" 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=rs2148352851" 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=RCV000011399" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011399" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011399</a>
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<p>Unlike other F9 promoter mutations which result in hemophilia B Leyden (see <a href="/entry/306900">306900</a>) (e.g., <a href="#0001">300746.0001</a>), this promoter mutation, a G-to-C change at -26, is accompanied by a bleeding tendency that is not ameliorated after puberty (<a href="#130" class="mim-tip-reference" title="Reijnen, M. J., Sladek, F. M., Bertina, R. M., Reitsma, P. H. <strong>Disruption of a binding site for hepatocyte nuclear factor 4 results in hemophilia B Leyden.</strong> Proc. Nat. Acad. Sci. 89: 6300-6303, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1631121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1631121</a>] [<a href="https://doi.org/10.1073/pnas.89.14.6300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1631121">Reijnen et al., 1992</a>). <a href="#130" class="mim-tip-reference" title="Reijnen, M. J., Sladek, F. M., Bertina, R. M., Reitsma, P. H. <strong>Disruption of a binding site for hepatocyte nuclear factor 4 results in hemophilia B Leyden.</strong> Proc. Nat. Acad. Sci. 89: 6300-6303, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1631121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1631121</a>] [<a href="https://doi.org/10.1073/pnas.89.14.6300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1631121">Reijnen et al. (1992)</a> demonstrated that this mutation disrupted the binding of hepatocyte nuclear factor-4 (HNF4; <a href="/entry/600281">600281</a>), a member of the steroid hormone receptor superfamily of transcription factors, which normally binds at nucleotides -34 to -10. Whereas HNF4 transactivated the wildtype promoter sequence in liver and nonliver (e.g., HeLa) cell types, it did not at all transactivate the -26 mutated promoter. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1631121" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#50" class="mim-tip-reference" title="Crossley, M., Ludwig, M., Stowell, K. M., De Vos, P., Olek, K., Brownlee, G. G. <strong>Recovery from hemophilia B Leyden: an androgen-responsive element in the factor IX promoter.</strong> Science 257: 377-379, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1631558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1631558</a>] [<a href="https://doi.org/10.1126/science.1631558" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1631558">Crossley et al. (1992)</a> provided an explanation for why the -20 promoter mutation shows recovery at puberty and the -26 Brandenburg mutation does not. Both mutations impair transcription by disrupting the binding site for the liver-enriched transcription factor LF-A1/HNF4. The -26 but not the -20 mutation also disrupts an androgen-responsive element, which overlaps the LF-A1/HNF4 site. This explains the failure of improvement in -26 patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1631558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0098 HEMOPHILIA B</strong>
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F9, ALU INSERTION, EX5
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<p>In a patient with severe hemophilia B (<a href="/entry/306900">306900</a>), <a href="#164" class="mim-tip-reference" title="Vidaud, D., Tartary, M., Costa, J.-M., Bahnak, B. R., Gispert-Sanchez, S., Fressinaud, E., Gazengel, C., Meyer, D., Goossens, M., Lavergne, J.-M., Vidaud, M. <strong>Nucleotide substitutions at the -6 position in the promoter region of the factor IX gene result in different severity of hemophilia B Leyden: consequences for genetic counseling.</strong> Hum. Genet. 91: 241-244, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8478007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8478007</a>] [<a href="https://doi.org/10.1007/BF00218264" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8478007">Vidaud et al. (1993)</a> discovered a de novo insertion of a human-specific Alu repeat element within exon 5 of the F9 gene. The element interrupted the reading frame of the mature factor IX at glutamic acid 96 resulting in a stop codon within the inserted sequence. The Alu repeat was 322 bp long and was thought to have been inserted through retroposition. Insertional mutagenesis involving an Alu element has been reported in type I neurofibromatosis (<a href="/entry/162200#0001">162200.0001</a>) and in gyrate atrophy (<a href="/entry/258870#0023">258870.0023</a>). The involvement of Alu elements in gene deletion through homologous recombination and unequal crossing-over has been demonstrated in familial hypercholesterolemia (e.g., <a href="/entry/143890#0029">143890.0029</a>) and ADA deficiency (<a href="/entry/102700#0008">102700.0008</a>). Also see <a href="#167" class="mim-tip-reference" title="Vidaud, M., Vidaud, D., Siguret, V., Lavergne, J. M., Goossens, M. <strong>Mutational insertion of an Alu sequence causes hemophilia B. (Abstract)</strong> Am. J. Hum. Genet. 45: A226, 1989."None>Vidaud et al. (1989)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8478007" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Note: This allelic variant was previously incorrectly in OMIM as EX51INS in 300746.0080.</p>
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<strong>.0099 HEMOPHILIA B</strong>
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HEMB, ILE-30ASN
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906480 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906480;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=rs387906480" 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=rs387906480" 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=RCV000011401" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011401" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011401</a>
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<p>Among the many mutations of the F9 gene described in hemophilia B (<a href="/entry/306900">306900</a>) (<a href="#68" class="mim-tip-reference" title="Giannelli, F., Green, P. M., High, K. A., Sommer, S., Lillicrap, D. P., Ludwig, M., Olek, K., Reitsma, P. H., Goossens, M., Yoshioka, A., Brownlee, G. G. <strong>Haemophilia B: database of point mutations and short additions and deletions--third edition, 1992.</strong> Nucleic Acids Res. 20: 2027-2063, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1598234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1598234</a>] [<a href="https://doi.org/10.1093/nar/20.suppl.2027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1598234">Giannelli et al., 1992</a>), the density of amino acid substitutions in the domains coded by the different exons is similar, except for exon 'a' where it is much lower. Exon 'a' codes for the predomain of the signal peptide that is necessary for the transport of factor IX to the endoplasmic reticulum and for its secretion. Comparison of the signal peptide of secreted proteins shows lack of conservation of the primary amino acid sequence, and the only constant features are the presence of a charged residue at the amino end and a core of 8-12 hydrophobic residues. In a patient with severe, antigen-negative hemophilia B, <a href="#76" class="mim-tip-reference" title="Green, P. M., Mitchell, V. E., McGraw, A., Goldman, E., Giannelli, F. <strong>Haemophilia B caused by a missense mutation in the prepeptide sequence of factor IX.</strong> Hum. Mutat. 2: 103-107, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8318985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8318985</a>] [<a href="https://doi.org/10.1002/humu.1380020207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8318985">Green et al. (1993)</a> found an A-to-T transversion causing substitution of isoleucine by asparagine at position -30. This change disrupted the hydrophobic core of the prepeptide, a feature required for secretion. Thus, hemophilia in this patient was caused by failure to secrete factor IX from the hepatocytes. Only one other amino acid substitution had been reported in the prepeptide of factor IX; a cys-to-arg mutation at position -19 affecting the cleavage site between the pre- and propeptide (cys-19/thr-18) caused mild hemophilia (<a href="#18" class="mim-tip-reference" title="Bottema, C. D. K., Bottema, M. J., Ketterling, R. P., Yoon, H.-S., Janco, R. L., Phillips, J. A., III, Sommer, S. S. <strong>Why does the human factor IX gene have a G+C content of 40%?</strong> Am. J. Hum. Genet. 49: 839-850, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1897528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1897528</a>]" pmid="1897528">Bottema et al., 1991</a>) (<a href="#0100">300746.0100</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1897528+1598234+8318985" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0100 HEMOPHILIA B</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">rs387906481 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906481;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=rs387906481" 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=rs387906481" 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=RCV000011402 OR RCV001851793" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011402, RCV001851793" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011402...</a>
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<p>See <a href="#0099">300746.0099</a>.</p>
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<strong>.0101 HEMOPHILIA B</strong>
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F9, VAL373GLU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852280 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852280;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=rs137852280" 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=rs137852280" 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=RCV000011403" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011403" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011403</a>
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<p><a href="#1" class="mim-tip-reference" title="Aguilar-Martinez, P., Romey, M.-C., Gris, J.-C., Schved, J.-F., Demaille, J., Claustres, M. <strong>A novel mutation (val373-to-glu) in the catalytic domain of factor IX, resulting in moderately/severe hemophilia B in a southern French patient.</strong> Hum. Mutat. 3: 156-158, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8199596/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8199596</a>] [<a href="https://doi.org/10.1002/humu.1380030211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8199596">Aguilar-Martinez et al. (1994)</a> identified a val373-to-glu mutation in a 40-year-old man in whom the diagnosis of hemophilia (<a href="/entry/306900">306900</a>) was made at the age of 4 and who had been suffering hemarthrosis since the age of 13. A first cousin was affected. The mutation was located in the serine protease catalytic domain of the F9 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8199596" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0102 WARFARIN SENSITIVITY, X-LINKED</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> rs367569299 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs367569299;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/rs367569299?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=rs367569299" 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=rs367569299" 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=RCV000990955 OR RCV001815016 OR RCV003117663" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000990955, RCV001815016, RCV003117663" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000990955...</a>
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<p><a href="#125" class="mim-tip-reference" title="Pezeshkpoor, B., Czogalla, K. J., Caspers, M., Berkemeier, A.-C., Liphardt, K., Ghosh, S., Kellner, M., Ulrich, S., Pavlova, A., Oldenburg, J. <strong>Variants in FIX propeptide associated with vitamin K antagonism hypersensitivity: functional analysis and additional data confirming the common founder mutations.</strong> Ann. Hemat. 97: 1061-1069, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29450643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29450643</a>] [<a href="https://doi.org/10.1007/s00277-018-3264-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29450643">Pezeshkpoor et al. (2018)</a> noted that ala-10thr (A-10T) is the legacy designation for ala37-to-thr (A37T). The A37T designation includes the F9 signal sequence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29450643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 propeptide sequences of the vitamin K-dependent clotting factors serve as a recognition site for the enzyme gamma-glutamyl carboxylase (<a href="/entry/137167">137167</a>), which catalyzes the carboxylation of glutamic acid residues in the amino terminus of the mature protein. <a href="#46" class="mim-tip-reference" title="Chu, K., Wu, S.-M., Stanley, T., Stafford, D. W., High, K. A. <strong>A mutation in the propeptide of factor IX leads to warfarin sensitivity by a novel mechanism.</strong> J. Clin. Invest. 98: 1619-1625, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8833911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8833911</a>] [<a href="https://doi.org/10.1172/JCI118956" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8833911">Chu et al. (1996)</a> described a mutation in the propeptide of factor IX that resulted in warfarin sensitivity (<a href="/entry/301052">301052</a>) because of reduced affinity of the carboxylase for the factor IX precursor. The patient was a 49-year-old with a congenital bicuspid aortic valve with accompanying aortic stenosis and regurgitation. After insertion of an artificial valve, he had bleeding complications when he was given warfarin for anticoagulation. The patient's family history was negative for bleeding diatheses. The patient had a factor IX activity level of more than 100% when not receiving warfarin and less than 1% when receiving warfarin, at a point where other vitamin K-dependent factors were at 30 to 40% activity levels. Direct sequence analysis of amplified genomic DNA from all 8 exons and exon-intron junctions showed a G-to-A transition at nucleotide 6346 resulting in an alanine-to-threonine change at residue -10 in the propeptide. To define the mechanism by which the mutation resulted in warfarin sensitivity, they analyzed wildtype and mutant recombinant peptides in an in vitro carboxylation reaction. The peptides that were analyzed included the wildtype sequence of F9, the ala-10thr sequence, and the ala-10gly substitution which reflects the sequence in bone gamma-carboxyglutamic acid protein (<a href="/entry/112260">112260</a>). Measurement of carbon dioxide incorporation at a range of peptide concentrations demonstrated about twice normal V(max) values for both A-10T and A-10G, whereas K(m) values showed a 33-fold difference between wildtype and the variants. These studies delineated a novel mechanism for warfarin sensitivity and explained the observation that bone gamma-carboxyglutamic acid protein is more sensitive to warfarin than the coagulation proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8833911" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Pezeshkpoor, B., Czogalla, K. J., Caspers, M., Berkemeier, A.-C., Liphardt, K., Ghosh, S., Kellner, M., Ulrich, S., Pavlova, A., Oldenburg, J. <strong>Variants in FIX propeptide associated with vitamin K antagonism hypersensitivity: functional analysis and additional data confirming the common founder mutations.</strong> Ann. Hemat. 97: 1061-1069, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29450643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29450643</a>] [<a href="https://doi.org/10.1007/s00277-018-3264-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29450643">Pezeshkpoor et al. (2018)</a> reported that 11 patients with X-linked warfarin sensitivity, including 6 patients previously by <a href="#121" class="mim-tip-reference" title="Oldenburg, J., Kriz, K., Wuillemin, W. A., Maly, F. E., von Felten, A., Siegemund, A., Keeling, D. M., Baker, P., Chu, K., Konkle, B. A., Lammle, B., Albert, T. <strong>Genetic predisposition to bleeding during oral anticoagulant therapy: evidence for common founder mutations (FIXVal-10 and FIXThr-10) and an independent CpG hotspot mutation (FIXThr-10).</strong> Thromb. Haemost. 85: 454-457, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11307814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11307814</a>]" pmid="11307814">Oldenburg et al. (2001)</a>, were found to have an A37T mutation in exon 2 of the F9 gene. The mutation, which occurs in a highly conserved region of the protein, was not identified in 1,834 female and 135 male healthy blood donors from different regions throughout Europe. Expression of F9 containing the A37T mutation in HEK293T cells resulted in a reduction in the FIX:C ratio and a reduced half maximal inhibitory concentration (IC50) for warfarin compared to HEK293T cells transfected with wildtype F9. This indicated a sensitivity to warfarin conferred by the A37T mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11307814+29450643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0103 WARFARIN SENSITIVITY, X-LINKED</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011406" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011406" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011406</a>
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<p><a href="#125" class="mim-tip-reference" title="Pezeshkpoor, B., Czogalla, K. J., Caspers, M., Berkemeier, A.-C., Liphardt, K., Ghosh, S., Kellner, M., Ulrich, S., Pavlova, A., Oldenburg, J. <strong>Variants in FIX propeptide associated with vitamin K antagonism hypersensitivity: functional analysis and additional data confirming the common founder mutations.</strong> Ann. Hemat. 97: 1061-1069, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29450643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29450643</a>] [<a href="https://doi.org/10.1007/s00277-018-3264-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29450643">Pezeshkpoor et al. (2018)</a> noted that ala-10val (A10V) is the legacy designation for ala37-to-val (A37V). The A37V designation includes the signal sequence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29450643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#122" class="mim-tip-reference" title="Oldenburg, J., Quenzel, E.-M., Harbrecht, U., Fregin, A., Kress, W., Muller, C. R., Hertefelder, H.-J., Schwaab, R., Brackmann, H.-H., Hanfland, P. <strong>Missense mutations at ala-10 in the factor IX propeptide: an insignificant variant in normal life but a decisive cause of bleeding during oral anticoagulant therapy.</strong> Brit. J. Haemat. 98: 240-244, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9233593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9233593</a>] [<a href="https://doi.org/10.1046/j.1365-2141.1997.2213036.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9233593">Oldenburg et al. (1997)</a> reported 3 patients in whom mutations in the factor IX propeptide was found to cause severe bleeding during coumarin therapy (<a href="/entry/301052">301052</a>). Strikingly, the bleeding occurred within the therapeutic ranges of the prothrombin time (PT) and international normalized ratio (INR). In all 3 patients, coumarin therapy caused an unusually selective decrease of factor IX activity to levels below 1 to 3%. Upon withdrawal of coumarin, factor IX levels increased to subnormal or normal values of 55, 85 and 125%, respectively. In 1 patient the ala-10-to-thr mutation (<a href="#0102">300746.0102</a>) was found; in 2 patients the missense mutation affecting the ala-10 residue was ala (GCC) to val (GTC). The mutation in the propeptide at a position that is essential for the carboxylase recognition site causes a reduced affinity of the carboxylase enzyme to the propeptide. This effect leads to an impaired carboxylase epoxidase reaction that is decisively triggered by the vitamin K concentration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9233593" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Pezeshkpoor, B., Czogalla, K. J., Caspers, M., Berkemeier, A.-C., Liphardt, K., Ghosh, S., Kellner, M., Ulrich, S., Pavlova, A., Oldenburg, J. <strong>Variants in FIX propeptide associated with vitamin K antagonism hypersensitivity: functional analysis and additional data confirming the common founder mutations.</strong> Ann. Hemat. 97: 1061-1069, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29450643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29450643</a>] [<a href="https://doi.org/10.1007/s00277-018-3264-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29450643">Pezeshkpoor et al. (2018)</a> reported that 7 patients with X-linked warfarin sensitivity, including 5 patients previously reported by <a href="#121" class="mim-tip-reference" title="Oldenburg, J., Kriz, K., Wuillemin, W. A., Maly, F. E., von Felten, A., Siegemund, A., Keeling, D. M., Baker, P., Chu, K., Konkle, B. A., Lammle, B., Albert, T. <strong>Genetic predisposition to bleeding during oral anticoagulant therapy: evidence for common founder mutations (FIXVal-10 and FIXThr-10) and an independent CpG hotspot mutation (FIXThr-10).</strong> Thromb. Haemost. 85: 454-457, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11307814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11307814</a>]" pmid="11307814">Oldenburg et al. (2001)</a>, were found to have an A37V mutation in exon 2 of the F9 gene. The mutation, which occurs in a highly conserved region of the protein, was not identified in 1,834 female and 135 male healthy blood donors from different regions throughout Europe. Expression of F9 containing the A37V mutation in HEK293T cells resulted in a reduction in the FIX:C ratio and a reduced half maximal inhibitory concentration (IC50) for warfarin compared to HEK293T cells transfected with wildtype F9. This indicated a sensitivity to warfarin conferred by the A37V mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11307814+29450643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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">rs137852281 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852281;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=rs137852281" 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=rs137852281" 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=RCV000011407" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011407" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011407</a>
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<p><a href="#36" class="mim-tip-reference" title="Chan, V., Chan, V. W. Y., Yip, B., Chim, C. S., Chan, T. K. <strong>Hemophilia B in a female carrier due to skewed inactivation of the normal X-chromosome.</strong> Am. J. Hemat. 58: 72-76, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590153/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590153</a>] [<a href="https://doi.org/10.1002/(sici)1096-8652(199805)58:1<72::aid-ajh13>3.0.co;2-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9590153">Chan et al. (1998)</a> found that a 20-year-old female student with mild hemophilia B (<a href="/entry/306900">306900</a>) was heterozygous for a mutation in codon 351 of the F9 gene: GCT (ala) was converted to CCT (pro). She had inherited the mutation from her carrier mother. Analysis of the methyl-sensitive HpaII sites at the 5-prime end of the hypoxanthine phosphoribosyltransferase gene (HPRT; <a href="/entry/308000">308000</a>) showed that skewed inactivation of the X chromosome carrying her normal F9 gene accounted for the hemophilia phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9590153" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0105 HEMOPHILIA B</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011408" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011408" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011408</a>
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<p><a href="#60" class="mim-tip-reference" title="Drost, J. B., Scaringe, W. A., Jaloma-Cruz, A. R., Li, X., Ossa, D. F., Kasper, C. K., Sommer, S. S. <strong>Novel hotspot detector software reveals a non-CpG hotspot of germline mutation in the factor IX gene (F9) in Latin Americans.</strong> Hum. Mutat. 16: 203-210, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10980527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10980527</a>] [<a href="https://doi.org/10.1002/1098-1004(200009)16:3<203::AID-HUMU3>3.0.CO;2-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10980527">Drost et al. (2000)</a> demonstrated that nucleotide 17747 of the F9 gene is a mutation hotspot for hemophilia B (<a href="/entry/306900">306900</a>) in all Latin American population samples but not in other populations. Two substitutions were observed, G-A and G-C (<a href="#0106">300746.0106</a>). The authors suggested that this was the first evidence of population-specific effects on germline mutation that causes human genetic disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10980527" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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=RCV000011405" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011405" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011405</a>
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<p>See (<a href="#0105">300746.0105</a>) and <a href="#60" class="mim-tip-reference" title="Drost, J. B., Scaringe, W. A., Jaloma-Cruz, A. R., Li, X., Ossa, D. F., Kasper, C. K., Sommer, S. S. <strong>Novel hotspot detector software reveals a non-CpG hotspot of germline mutation in the factor IX gene (F9) in Latin Americans.</strong> Hum. Mutat. 16: 203-210, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10980527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10980527</a>] [<a href="https://doi.org/10.1002/1098-1004(200009)16:3<203::AID-HUMU3>3.0.CO;2-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10980527">Drost et al. (2000)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10980527" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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">rs587776735 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776735;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=rs587776735" 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=rs587776735" 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=RCV000011409" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011409" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011409</a>
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<p>In a woman with moderately severe hemophilia B (<a href="/entry/306900">306900</a>), <a href="#48" class="mim-tip-reference" title="Costa, J.-M., Vidaud, D., Laurendeau, I., Vidaud, M., Fressinaud, E., Moisan, J.-P., David, A., Meyer, D., Lavergne, J.-M. <strong>Somatic mosaicism and compound heterozygosity in female hemophilia B.</strong> Blood 96: 1585-1587, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10942410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10942410</a>]" pmid="10942410">Costa et al. (2000)</a> found a T-to-C transition at position +2 in the 5-prime splice site of intron 3 (6704T-C) and an ile344-to-thr missense mutation (<a href="/entry/306900#0108">306900.0108</a>). The splice site mutation came from the mother who was a somatic mosaic; the missense mutation appeared to be a de novo mutation from the father. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10942410" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 B</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">rs387906482 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906482;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=rs387906482" 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=rs387906482" 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=RCV000011410" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011410" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011410</a>
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<p>See <a href="#0107">300746.0107</a> and <a href="#48" class="mim-tip-reference" title="Costa, J.-M., Vidaud, D., Laurendeau, I., Vidaud, M., Fressinaud, E., Moisan, J.-P., David, A., Meyer, D., Lavergne, J.-M. <strong>Somatic mosaicism and compound heterozygosity in female hemophilia B.</strong> Blood 96: 1585-1587, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10942410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10942410</a>]" pmid="10942410">Costa et al. (2000)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10942410" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0109 HEMOPHILIA B</strong>
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F9, CYS206SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606792 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606792;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=rs267606792" 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=rs267606792" 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=RCV000011411" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011411" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011411</a>
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<p><a href="#154" class="mim-tip-reference" title="Taylor, S. A. M., Duffin, J., Cameron, C., Teitel, J., Garvey, B., Lillicrap, D. P. <strong>Characterization of the original Christmas disease mutation (cysteine 206-to-serine): from clinical recognition to molecular pathogenesis.</strong> Thromb. Haemost. 67: 63-65, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1615485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1615485</a>]" pmid="1615485">Taylor et al. (1992)</a> found that the causative mutation in the first reported patient with Christmas disease (<a href="/entry/306900">306900</a>) (<a href="#17" class="mim-tip-reference" title="Biggs, R., Douglas, A. S., Macfarlane, R. G., Dacie, J. V., Pitney, W. R., Merskey, C., O'Brien, J. R. <strong>Christmas disease: a condition previously mistaken for haemophilia.</strong> Brit. Med. J. 2: 1378-1382, 1952.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12997790/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12997790</a>] [<a href="https://doi.org/10.1136/bmj.2.4799.1378" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12997790">Biggs et al., 1952</a>) was a cys206-to-ser change in the F9 gene. The patient died at the age of 46 years from acquired immunodeficiency syndrome, contracted through treatment with blood products (<a href="#65" class="mim-tip-reference" title="Giangrande, P. L. F. <strong>Historical review: six characters in search of an author: the history of the nomenclature of coagulation factors.</strong> Brit. J. Haemat. 121: 703-712, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12780784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12780784</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2003.04333.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12780784">Giangrande, 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1615485+12997790+12780784" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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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<strong>.0110 HEMOPHILIA B</strong>
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F9, 2-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">rs587776736 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776736;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=rs587776736" 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=rs587776736" 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=RCV000011412" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011412" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011412</a>
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<p><a href="#53" class="mim-tip-reference" title="Cutler, J. A., Mitchell, M. J., Smith, M. P., Savidge, G. F. <strong>Germline mosaicism resulting in the transmission of severe hemophilia B from a grandfather with a mild deficiency.</strong> Am. J. Med. Genet. 129A: 13-15, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15266608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15266608</a>] [<a href="https://doi.org/10.1002/ajmg.a.30162" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15266608">Cutler et al. (2004)</a> described a family in which the maternal grandfather of a severely affected infant with hemophilia B (<a href="/entry/306900">306900</a>) was a somatic and germline mosaic and had very mild factor IX deficiency. The maternal grandfather was apparently a somatic and germline mosaic for the family mutation, a 2-bp deletion (AG within codons 134-135) in the F9 gene causing a frameshift mutation and the creation of a premature termination sequence in exon 6 at codon 141. One daughter, the mother of the proband, was a carrier of the mutation; the other daughter, was not a carrier. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15266608" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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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<span class="mim-font">
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<strong>.0111 HEMOPHILIA B</strong>
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F9, ARG338PRO
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852283 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852283;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=rs137852283" 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=rs137852283" 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=RCV000011413" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011413" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011413</a>
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<p>In a patient with a mild form of hemophilia B (<a href="/entry/306900">306900</a>), <a href="#90" class="mim-tip-reference" title="Ketterling, R. P., Vielhaber, E. L., Lind, T. J., Thorland, E. C., Sommer, S. S. <strong>The rates and patterns of deletions in the human factor IX gene.</strong> Am. J. Hum. Genet. 54: 201-213, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8304338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8304338</a>]" pmid="8304338">Ketterling et al. (1994)</a> identified a G-to-C transversion in the F9 gene, resulting in an arg338-to-pro (R338P) substitution. There was 16% residual F9 activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8304338" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 THROMBOPHILIA, X-LINKED, DUE TO FACTOR IX DEFECT</strong>
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F9, ARG338LEU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852283 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852283;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=rs137852283" 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=rs137852283" 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=RCV000011414 OR RCV000119810" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011414, RCV000119810" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011414...</a>
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<p>This mutation is known as factor IX Padua.</p><p>In a 21-year-old Italian man with thrombophilia and a deep venous thrombosis in the right leg (<a href="/entry/300807">300807</a>), <a href="#140" class="mim-tip-reference" title="Simioni, P., Tormene, D., Tognin, G., Gavasso, S., Bulato, C., Iacobelli, N. P., Finn, J. D., Spiezia, L., Radu, C., Arruda, V. R. <strong>X-linked thrombophilia with a mutant factor IX (factor IX Padua).</strong> New Eng. J. Med. 361: 1671-1675, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19846852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19846852</a>] [<a href="https://doi.org/10.1056/NEJMoa0904377" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19846852">Simioni et al. (2009)</a> identified a hemizygous 31134G-T transversion in exon 8 of the F9 gene, resulting in an arg338-to-leu (R338L) substitution. Coagulation studies showed that he had normal levels of F9 antigen, but very high levels of F9 activity (776% of control values). His 11-year-old brother and mother, who were hemizygous and heterozygous for the mutation, respectively, also had normal F9 antigen levels and increased F9 activity levels (551% and 337%, respectively). The mutation was not found in 200 control individuals or in 200 patients with documented thromboembolism. In vitro functional expression studies showed that the mutant F9 had 8-fold increased activity compared to wildtype, consistent with a gain of function. The affected residue is important for binding to F10 (see <a href="/entry/227600">227600</a>), and the R338L substitution apparently increases the efficiency of this binding. <a href="#140" class="mim-tip-reference" title="Simioni, P., Tormene, D., Tognin, G., Gavasso, S., Bulato, C., Iacobelli, N. P., Finn, J. D., Spiezia, L., Radu, C., Arruda, V. R. <strong>X-linked thrombophilia with a mutant factor IX (factor IX Padua).</strong> New Eng. J. Med. 361: 1671-1675, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19846852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19846852</a>] [<a href="https://doi.org/10.1056/NEJMoa0904377" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19846852">Simioni et al. (2009)</a> noted that another mutation at this residue, R338P (<a href="#0111">300746.0111</a>), results in hemophilia B (<a href="/entry/306900">306900</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19846852" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 B</strong>
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F9, IVS3, A-G, -3
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs398122990 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398122990;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=rs398122990" 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=rs398122990" 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=RCV000077844 OR RCV001072034" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000077844, RCV001072034" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000077844...</a>
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<p>Although the X-linked blood disorder known as the 'royal disease' transmitted from Queen Victoria (1819-1901) to European royal families had been known to be a form of hemophilia, its molecular basis had not been established. In the remains of the Russian Empress Alexandra, granddaughter of Queen Victoria, and her son, Crown Prince Alexei, <a href="#133" class="mim-tip-reference" title="Rogaev, E. I., Grigorenko, A. P., Faskhutdinova, G., Kittler, E. L. W., Moliaka, Y. K. <strong>Genotype analysis identifies the cause of the 'Royal disease.'</strong> Science 326: 817 only, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19815722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19815722</a>] [<a href="https://doi.org/10.1126/science.1180660" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19815722">Rogaev et al. (2009)</a> identified an A-to-G transition at the -3 position of intron 3 of the F9 gene. The mutation activated a cryptic splice acceptor site, shifting the open reading frame of the F9 mRNA and leading to a premature stop codon. The mutation was also identified in one of Alexei's sisters, presumed to be Anastasia. The identification of this mutation in the F9 gene allowed the recognition of the 'royal disease' as a severe form of hemophilia B, also known as 'Christmas disease' (<a href="/entry/306900">306900</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19815722" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>See Also:</strong>
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<a href="#Anson1985" class="mim-tip-reference" title="Anson, D. S., Austen, D. E. G., Brownlee, G. G. <strong>Expression of active human clotting factor IX from recombinant DNA clones in mammalian cells.</strong> Nature 315: 683-685, 1985.">Anson et al. (1985)</a>; <a href="#Bertina1979" class="mim-tip-reference" title="Bertina, R. M., Briet, E., Veltkamp, J. J. <strong>Variants of vitamin K dependent coagulation factors. (Editorial)</strong> Acta Haemat. 62: 1-3, 1979.">Bertina et al. (1979)</a>; <a href="#Bertina1982" class="mim-tip-reference" title="Bertina, R. M., van der Linden, I. K. <strong>Factor IX Deventer--evidence for the heterogeneity of hemophilia B(M).</strong> Thromb. Haemost. 47: 136-140, 1982.">Bertina and van der
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Linden (1982)</a>; <a href="#Bertina1978" class="mim-tip-reference" title="Bertina, R. M., Veltkamp, J. J. <strong>The abnormal factor IX of hemophilia B+ variants.</strong> Thromb. Haemost. 40: 335-349, 1978.">Bertina and Veltkamp (1978)</a>; <a href="#Bottema1990" class="mim-tip-reference" title="Bottema, C. D. K., Koeberl, D. D., Ketterling, R. P., Bowie, E. J. W., Taylor, S. A. M., Lillicrap, D., Shapiro, A., Gilchrist, G., Sommer, S. S. <strong>A past mutation at isoleucine-397 is now a common cause of moderate/mild haemophilia B.</strong> Brit. J. Haemat. 75: 212-216, 1990.">Bottema et al. (1990)</a>; <a href="#Bottema1989" class="mim-tip-reference" title="Bottema, C. D. K., Koeberl, D. D., Sommer, S. S. <strong>Direct carrier testing in 14 families with haemophilia B.</strong> Lancet 334: 526-529, 1989. Note: Originally Volume 2.">Bottema et al. (1989)</a>; <a href="#Braunstein1981" class="mim-tip-reference" title="Braunstein, K. M., Noyes, C. M., Griffith, M. J., Lundblad, R. L., Roberts, H. R. <strong>Characterization of the defect in activation of factor IX(Chapel Hill) by human factor XIa.</strong> J. Clin. Invest. 68: 1420-1426, 1981.">Braunstein et al. (1981)</a>; <a href="#Bray1986" class="mim-tip-reference" title="Bray, G. L., Thompson, A. R. <strong>Partial factor IX protein in a pedigree with hemophilia B due to a partial gene deletion.</strong> J. Clin. Invest. 77: 1194-1200, 1986.">Bray and Thompson
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(1986)</a>; <a href="#Brinkhous1973" class="mim-tip-reference" title="Brinkhous, K. M., Davis, P. D., Graham, J. B., Dodds, W. J. <strong>Expression and linkage of genes for X-linked hemophilias A and B in the dog.</strong> Blood 41: 577-585, 1973.">Brinkhous et al. (1973)</a>; <a href="#Camerino1985" class="mim-tip-reference" title="Camerino, G., Oberle, I., Drayna, D., Mandel, J. L. <strong>A new MspI restriction fragment length polymorphism in the hemophilia B locus.</strong> Hum. Genet. 71: 79-81, 1985.">Camerino et al. (1985)</a>; <a href="#Chan1989" class="mim-tip-reference" title="Chan, V., Chan, T. K., Tong, T. M. F., 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.">Chan et al.
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(1989)</a>; <a href="#Chen1989" class="mim-tip-reference" title="Chen, S.-H., Thompson, A. R. <strong>Personal Communication.</strong> Seattle, Wash. 11/1989.">Chen et al. (1989)</a>; <a href="#Choo1987" class="mim-tip-reference" title="Choo, K. H., Raphael, K., McAdam, W., Peterson, M. G. <strong>Expression of active human blood clotting factor IX in transgenic mice: use of a cDNA with complete mRNA sequence.</strong> Nucleic Acids Res. 15: 871-884, 1987.">Choo et al. (1987)</a>; <a href="#Drayna1984" class="mim-tip-reference" title="Drayna, D., Davies, K., Hartley, D., Mandel, J.-L., Camerino, G., Williamson, R., White, R. <strong>Genetic mapping of the human X chromosome by using restriction fragment length polymorphisms.</strong> Proc. Nat. Acad. Sci. 81: 2836-2839, 1984.">Drayna et al. (1984)</a>; <a href="#Giannelli1999" class="mim-tip-reference" title="Giannelli, F., Anagnostopoulos, T., Green, P. M. <strong>Mutation rates in humans. II. Sporadic mutation-specific rates and rate of detrimental human mutations inferred from hemophilia B.</strong> Am. J. Hum. Genet. 65: 1580-1587, 1999.">Giannelli et al. (1999)</a>; <a href="#Graham1962" class="mim-tip-reference" title="Graham, J. B., Tarleton, H. L., Race, R. R., Sanger, R. <strong>A human double cross-over.</strong> Nature 195: 834, 1962.">Graham et al. (1962)</a>; <a href="#Gray1989" class="mim-tip-reference" title="Gray, M. W., Winship, P. R. <strong>CpG polymorphisms and haemophilia B. (Letter)</strong> Lancet 334: 502-503, 1989. Note: Originally Volume 2.">Gray and Winship
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(1989)</a>; <a href="#Green1999" class="mim-tip-reference" title="Green, P. M., Saad, S., Lewis, C. M., Giannelli, F. <strong>Mutation rates in humans. I. Overall and sex-specific rates obtained from a population study of hemophilia B.</strong> Am. J. Hum. Genet. 65: 1572-1579, 1999.">Green et al. (1999)</a>; <a href="#Kling1992" class="mim-tip-reference" title="Kling, S., Ljung, R., Sjorin, E., Montandon, J., Green, P., Giannelli, F., Nilsson, I. M. <strong>Origin of mutation in sporadic cases of haemophilia-B.</strong> Europ. J. Haemat. 48: 142-145, 1992.">Kling et al. (1992)</a>; <a href="#Koeberl1990" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Sommer, S. S. <strong>Comparison of direct and indirect methods of carrier detection in an X-linked disease.</strong> Am. J. Med. Genet. 35: 600-608, 1990.">Koeberl et al.
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(1990)</a>; <a href="#Koeberl1990" class="mim-tip-reference" title="Koeberl, D. D., Bottema, C. D. K., Sommer, S. S. <strong>Comparison of direct and indirect methods of carrier detection in an X-linked disease.</strong> Am. J. Med. Genet. 35: 600-608, 1990.">Koeberl et al. (1990)</a>; <a href="#Liebman1985" class="mim-tip-reference" title="Liebman, H. A., Limentani, S. A., Furie, B. C., Furie, B. <strong>Immunoaffinity purification of factor IX (Christmas factor) by using conformation-specific antibodies directed against the factor IX-metal complex.</strong> Proc. Nat. Acad. Sci. 82: 3879-3883, 1985.">Liebman et al. (1985)</a>; <a href="#Little1992" class="mim-tip-reference" title="Little, R. D., Pilia, G., Johnson, S., D'Urso, M., Schlessinger, D. <strong>Yeast artificial chromosomes spanning 8 megabases and 10-15 centimorgans of human cytogenetic band Xq26.</strong> Proc. Nat. Acad. Sci. 89: 177-181, 1992.">Little et al.
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(1992)</a>; <a href="#Mandalaki1986" class="mim-tip-reference" title="Mandalaki, T., Louizou, C., Dimitriadou, C., Briet, E. <strong>Haemophilia B Leyden in Greece.</strong> Thromb. Haemost. 56: 340-342, 1986.">Mandalaki et al. (1986)</a>; <a href="#Mattei1985" class="mim-tip-reference" title="Mattei, M. G., Baeteman, M. A., Heilig, R., Oberle, I., Davies, K., Mandel, J. L., Mattei, J. F. <strong>Localization by in situ hybridization of the coagulation factor IX gene and of two polymorphic DNA probes with respect to the fragile X site.</strong> Hum. Genet. 69: 327-331, 1985.">Mattei et al. (1985)</a>; <a href="#Smith1985" class="mim-tip-reference" title="Smith, K. J. <strong>Monoclonal antibodies to coagulation factor IX define a high-frequency polymorphism by immunoassays.</strong> Am. J. Hum. Genet. 37: 668-679, 1985.">Smith (1985)</a>; <a href="#Spitzer1988" class="mim-tip-reference" title="Spitzer, S. G., Warn-Cramer, B. J., Kasper, C. C., Pendurthi, U. R., Bajaj, S. P. <strong>Mutations in the catalytic domain of factor IXa which prevent macromolecular catalysis. (Abstract)</strong> Circulation 78 (suppl. II): 118, 1988.">Spitzer et al. (1988)</a>; <a href="#Thompson1987" class="mim-tip-reference" title="Thompson, A. R. <strong>Alloantibodies in hemophilia B binding to multiple factor IX epitopes.</strong> Thromb. Res. 46: 169-174, 1987.">Thompson (1987)</a>; <a href="#Usharani1985" class="mim-tip-reference" title="Usharani, P., Warn-Cramer, B. J., Kasper, C. K., Bajaj, S. P. <strong>Characterization of three abnormal factor IX variants (Bm Lake Elsinore, Long Beach, and Los Angeles) of hemophilia-B: evidence for defects affecting the latent catalytic site.</strong> J. Clin. Invest. 75: 76-83, 1985.">Usharani et al. (1985)</a>; <a href="#Vidaud1993" class="mim-tip-reference" title="Vidaud, D., Vidaud, M., Bahnak, B. R., Siguret, V., Sanchez, S. G., Laurian, Y., Meyer, D., Goossens, M., Lavergne, J. M. <strong>Haemophilia B due to a de novo insertion of a human-specific Alu subfamily member within the coding region of the factor IX gene.</strong> Europ. J. Hum. Genet. 1: 30-36, 1993.">Vidaud et al. (1993)</a>; <a href="#Vogel1986" class="mim-tip-reference" title="Vogel, F., Motulsky, A. G. <strong>Population genetics. In: Vogel, F.; Motulsky, A. G.: Human Genetics.</strong> Berlin: Springer (pub.) 1986. Pp. 433-511.">Vogel and Motulsky (1986)</a>; <a href="#Wang1997" class="mim-tip-reference" title="Wang, L., Zoppe, M., Hackeng, T. M., Griffin, J. H., Lee, K.-F., Verma, I. M. <strong>A factor IX-deficient mouse model for hemophilia B gene therapy.</strong> Proc. Nat. Acad. Sci. 94: 11563-11566, 1997.">Wang et al. (1997)</a>; <a href="#Yoshioka1986" class="mim-tip-reference" title="Yoshioka, A., Ohkubo, Y., Nishimura, T., Tanaka, I., Fukui, H., Ogata, K., Kamiya, T., Takahashi, H. <strong>Heterogeneity of factor IX BM: difference in cleavage sites by factor XIa and Ca(2+) in factor IX Kashihara, factor IX Nagoya and factor IX Niigata.</strong> Thromb. Res. 42: 595-604, 1986.">Yoshioka et al. (1986)</a>
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Aguilar-Martinez, P., Romey, M.-C., Gris, J.-C., Schved, J.-F., Demaille, J., Claustres, M.
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<strong>A novel mutation (val373-to-glu) in the catalytic domain of factor IX, resulting in moderately/severe hemophilia B in a southern French patient.</strong>
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Hum. Mutat. 3: 156-158, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8199596/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8199596</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8199596" 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.1380030211" target="_blank">Full Text</a>]
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Anson, D. S., Austen, D. E. G., Brownlee, G. G.
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<strong>Expression of active human clotting factor IX from recombinant DNA clones in mammalian cells.</strong>
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Nature 315: 683-685, 1985.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2989700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2989700</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2989700" 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/10.1038/315683a0" target="_blank">Full Text</a>]
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Anson, D. S., Blake, D. J., Winship, P. R., Birnbaum, D., Brownlee, G. G.
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<strong>Nullisomic deletion of the mcf.2 transforming gene in two haemophilia B patients.</strong>
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EMBO J. 7: 2795-2799, 1988.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2846283/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2846283</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2846283" 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/j.1460-2075.1988.tb03134.x" target="_blank">Full Text</a>]
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Anson, D. S., Choo, K. H., Rees, D. J. G., Giannelli, F., Gould, K., Huddleston, J. A., Brownlee, G. G.
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<strong>The gene structure of human anti-haemophilic factor IX.</strong>
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EMBO J. 3: 1053-1060, 1984.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6329734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6329734</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6329734" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/j.1460-2075.1984.tb01926.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Attree1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Attree, O., Vidaud, D., Vidaud, M., Amselem, S., Lavergne, J.-M., Goossens, M.
|
|
<strong>Mutations in the catalytic domain of human coagulation factor IX: rapid characterization by direct genomic sequencing of DNA fragments displaying an altered melting behavior.</strong>
|
|
Genomics 4: 266-272, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2714791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2714791</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2714791" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(89)90330-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Attree1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Attree, O., Vidaud, M., Vidaud, D., Lavergne, J. M., Goossens, M.
|
|
<strong>New strategies for rapid detection and characterization of mutations in hemophilia B. (Abstract)</strong>
|
|
Thromb. Haemost. 62: 8, 1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Bentley1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bentley, A. K., Rees, D. J. G., Rizza, C., Brownlee, G. G.
|
|
<strong>Defective propeptide processing of blood clotting factor IX caused by mutation of arginine to glutamine at position -4.</strong>
|
|
Cell 45: 343-348, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3009023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3009023</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3009023" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0092-8674(86)90319-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Bernardi1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bernardi, F., Del Senno, L., Barbieri, R., Buzzoni, D., Gambari, R., Marchetti, G., Conconi, F., Panicucci, F., Positano, M., Pitruzzello, S.
|
|
<strong>Gene deletion in an Italian haemophilia B subject.</strong>
|
|
J. Med. Genet. 22: 305-307, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4045960/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4045960</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4045960" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.22.4.305" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Bertina1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bertina, R. M., Briet, E., Veltkamp, J. J.
|
|
<strong>Variants of vitamin K dependent coagulation factors. (Editorial)</strong>
|
|
Acta Haemat. 62: 1-3, 1979.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Bertina1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bertina, R. M., van der Linden, I. K., Mannucci, P. M., Reinalda-Poot, H. H., Cupers, R., Poort, S. R., Reitsma, P. H.
|
|
<strong>Mutations in haemophilia B-M occur at the 180arg-to-val activation site or in the catalytic domain. (Abstract)</strong>
|
|
Thromb. Haemost. 62: 203, 1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Bertina1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bertina, R. M., van der Linden, I. K., Mannucci, P. M., Reinalda-Poot, H. H., Cupers, R., Poort, S. R., Reitsma, P. H.
|
|
<strong>Mutations in hemophilia B(m) occur at the arg(180)-to-val activation site or in the catalytic domain of factor IX.</strong>
|
|
J. Biol. Chem. 265: 10876-10883, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2162822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2162822</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2162822" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Bertina1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bertina, R. M., van der Linden, I. K.
|
|
<strong>Factor IX Deventer--evidence for the heterogeneity of hemophilia B(M).</strong>
|
|
Thromb. Haemost. 47: 136-140, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7101232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7101232</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7101232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Bertina1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bertina, R. M., Veltkamp, J. J.
|
|
<strong>The abnormal factor IX of hemophilia B+ variants.</strong>
|
|
Thromb. Haemost. 40: 335-349, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/734633/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">734633</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=734633" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Bertina1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bertina, R. M.
|
|
<strong>Personal Communication.</strong>
|
|
Leiden, The Netherlands 1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Bezemer2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bezemer, I. D., Arellano, A. R., Tong, C. H., Rowland, C. M., Ireland, H. A., Bauer, K. A., Catanese, J., Reitsma, P. H., Doggen, C. J. M., Devlin, J. J., Rosendaal, F. R., Bare, L. A.
|
|
<strong>F9 Malmo, factor IX and deep vein thrombosis.</strong>
|
|
Haematologica 94: 693-699, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19286883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19286883</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19286883[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19286883" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.3324/haematol.2008.003020" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Bezemer2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bezemer, I. D., Bare, L. A., Doggen, C. J. M., Arellano, A. R., Tong, C., Rowland, C. M., Catanese, J., Young, B. A., Reitsma, P. H., Devlin, J. J., Rosendaal, F. R.
|
|
<strong>Gene variants associated with deep vein thrombosis.</strong>
|
|
JAMA 299: 1306-1314, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18349091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18349091</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18349091" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/jama.299.11.1306" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Biggs1952" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Biggs, R., Douglas, A. S., Macfarlane, R. G., Dacie, J. V., Pitney, W. R., Merskey, C., O'Brien, J. R.
|
|
<strong>Christmas disease: a condition previously mistaken for haemophilia.</strong>
|
|
Brit. Med. J. 2: 1378-1382, 1952.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12997790/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12997790</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12997790" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/bmj.2.4799.1378" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Bottema1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bottema, C. D. K., Bottema, M. J., Ketterling, R. P., Yoon, H.-S., Janco, R. L., Phillips, J. A., III, Sommer, S. S.
|
|
<strong>Why does the human factor IX gene have a G+C content of 40%?</strong>
|
|
Am. J. Hum. Genet. 49: 839-850, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1897528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1897528</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1897528" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Bottema1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bottema, C. D. K., Ketterling, R. P., Ii, S., Yoon, H.-S., Phillips, J. A., III, Sommer, S. S.
|
|
<strong>Missense mutations and evolutionary conservation of amino acids: evidence that many of the amino acids in factor IX function as 'spacer' elements.</strong>
|
|
Am. J. Hum. Genet. 49: 820-838, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1680287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1680287</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1680287" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Bottema1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bottema, C. D. K., Ketterling, R. P., Vielhaber, E., Yoon, H.-S., Gostout, B., Jacobson, D. P., Shapiro, A., Sommer, S. S.
|
|
<strong>The pattern of spontaneous germ-line mutation: relative rates of mutation at or near CpG dinucleotides in the factor IX gene.</strong>
|
|
Hum. Genet. 91: 496-503, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8314564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8314564</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8314564" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00217779" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Bottema1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bottema, C. D. K., Ketterling, R. P., Yoon, H.-S., Sommer, S. S.
|
|
<strong>The pattern of factor IX germ-line mutation in Asians is similar to that of Caucasians.</strong>
|
|
Am. J. Hum. Genet. 47: 835-841, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2220823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2220823</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2220823" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Bottema1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bottema, C. D. K., Koeberl, D. D., Ketterling, R. P., Bowie, E. J. W., Taylor, S. A. M., Lillicrap, D., Shapiro, A., Gilchrist, G., Sommer, S. S.
|
|
<strong>A past mutation at isoleucine-397 is now a common cause of moderate/mild haemophilia B.</strong>
|
|
Brit. J. Haemat. 75: 212-216, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2372508/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2372508</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2372508" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1990.tb02651.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Bottema1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bottema, C. D. K., Koeberl, D. D., Ketterling, R. P., Lillicrap, D. P., Bridges, P., Sommer, S. S.
|
|
<strong>The molecular pathology of hemophilia B is a mirror of the pattern of recent germline mutations in humans. (Abstract)</strong>
|
|
Blood 74: 252A, 1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Bottema1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bottema, C. D. K., Koeberl, D. D., Sommer, S. S.
|
|
<strong>Direct carrier testing in 14 families with haemophilia B.</strong>
|
|
Lancet 334: 526-529, 1989. Note: Originally Volume 2.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2570235/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2570235</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2570235" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0140-6736(89)90653-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Boyd1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Boyd, Y., Buckle, V. J., Munro, E. A., Choo, K. H., Migeon, B. R., Craig, I. W.
|
|
<strong>Assignment of the haemophilia B (factor IX) locus to the q26-qter region of the X chromosome.</strong>
|
|
Ann. Hum. Genet. 48: 145-152, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6331274/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6331274</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6331274" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1469-1809.1984.tb01009.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Braunstein1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Braunstein, K. M., Noyes, C. M., Griffith, M. J., Lundblad, R. L., Roberts, H. R.
|
|
<strong>Characterization of the defect in activation of factor IX(Chapel Hill) by human factor XIa.</strong>
|
|
J. Clin. Invest. 68: 1420-1426, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6976355/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6976355</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6976355" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/jci110393" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Bray1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bray, G. L., Thompson, A. R.
|
|
<strong>Partial factor IX protein in a pedigree with hemophilia B due to a partial gene deletion.</strong>
|
|
J. Clin. Invest. 77: 1194-1200, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3514676/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3514676</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3514676" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI112421" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Briet1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Briet, E., Bertina, R. M., van Tilburg, N. H., Veltkamp, J. J.
|
|
<strong>Hemophilia B Leyden: a sex-linked hereditary disorder that improves after puberty.</strong>
|
|
New Eng. J. Med. 306: 788-790, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7062952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7062952</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7062952" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM198204013061306" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Brinkhous1973" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brinkhous, K. M., Davis, P. D., Graham, J. B., Dodds, W. J.
|
|
<strong>Expression and linkage of genes for X-linked hemophilias A and B in the dog.</strong>
|
|
Blood 41: 577-585, 1973.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4688873/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4688873</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4688873" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Brooks2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brooks, M. B., Gu, W., Barnas, J. L., Ray, J., Ray, K.
|
|
<strong>A line 1 insertion in the factor IX gene segregates with mild hemophilia B in dogs.</strong>
|
|
Mammalian Genome 14: 788-795, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14722728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14722728</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14722728" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s00335-003-2290-z" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Brownlee1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brownlee, G. G.
|
|
<strong>Haemophilia B: a review of patient defects, diagnosis with gene probes and prospects for gene therapy.</strong>
|
|
Recent Adv. Haemat. 5: 251-265, 1988.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Camerino1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Camerino, G., Grzeschik, K. H., Jaye, M., de la Salle, H., Tolstoshev, P., Lecocq, J. P., Heilig, R., Mandel, J. L.
|
|
<strong>Regional localization on the human X chromosome and polymorphism of the coagulation factor IX gene (hemophilia B locus).</strong>
|
|
Proc. Nat. Acad. Sci. 81: 498-502, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6320191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6320191</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6320191" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.81.2.498" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Camerino1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Camerino, G., Mattei, M. G., Mattei, J. F., Jaye, M., Mandel, J. L.
|
|
<strong>Genetics of the fragile X-mental retardation syndrome: close linkage to hemophilia B and transmission through a normal male.</strong>
|
|
Nature 306: 701-704, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6689201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6689201</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6689201" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/306701a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Camerino1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Camerino, G., Oberle, I., Drayna, D., Mandel, J. L.
|
|
<strong>A new MspI restriction fragment length polymorphism in the hemophilia B locus.</strong>
|
|
Hum. Genet. 71: 79-81, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2411652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2411652</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2411652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00295673" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Chan1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chan, V., Chan, T. K., Tong, T. M. F., 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>, <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'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Chan1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chan, V., Chan, V. W. Y., Yip, B., Chim, C. S., Chan, T. K.
|
|
<strong>Hemophilia B in a female carrier due to skewed inactivation of the normal X-chromosome.</strong>
|
|
Am. J. Hemat. 58: 72-76, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590153/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590153</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9590153" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(sici)1096-8652(199805)58:1<72::aid-ajh13>3.0.co;2-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Chance1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chance, P. F., Dyer, K. A., Kurachi, K., Yoshitake, S., Ropers, H.-H., Wieacker, P., Gartler, S. M.
|
|
<strong>Regional localization of the human factor IX gene by molecular hybridization.</strong>
|
|
Hum. Genet. 65: 207-208, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6686210/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6686210</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6686210" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00286666" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Chen1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chen, S.-H., Scott, C. R., Edson, J. R., Kurachi, K.
|
|
<strong>An insertion within the factor IX gene: hemophilia B(El Salvador).</strong>
|
|
Am. J. Hum. Genet. 42: 581-584, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2831715/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2831715</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2831715" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Chen1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chen, S.-H., Scott, C. R., Schoof, J., Lovrien, E. W., Kurachi, K.
|
|
<strong>Factor IX(Portland): a nonsense mutation (CGA to TGA) resulting in hemophilia B.</strong>
|
|
Am. J. Hum. Genet. 44: 567-569, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2929599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2929599</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2929599" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Chen1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chen, S.-H., Thompson, A. R., Zhang, M., Scott, C. R.
|
|
<strong>Three point mutations in the factor IX genes of five hemophilia B patients: identification strategy using localization by altered epitopes in their hemophilic proteins.</strong>
|
|
J. Clin. Invest. 84: 113-118, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2472424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2472424</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2472424" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI114130" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Chen1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chen, S.-H., Thompson, A. R.
|
|
<strong>Personal Communication.</strong>
|
|
Seattle, Wash. 11/1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Chen1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chen, S.-H., Yoshitake, S., Chance, P. F., Bray, G. L., Thompson, A. R., Scott, C. R., Kurachi, K.
|
|
<strong>An intragenic deletion of the factor IX gene in a family with hemophilia B.</strong>
|
|
J. Clin. Invest. 76: 2161-2164, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3001143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3001143</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3001143" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI112222" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Chen1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chen, S.-H., Zhang, M., Lovrien, E. W., Scott, C. R., Thompson, A. R.
|
|
<strong>CG dinucleotide transitions in the factor IX gene account for about half of the point mutations in hemophilia B patients: a Seattle series.</strong>
|
|
Hum. Genet. 87: 177-182, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2066105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2066105</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2066105" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00204177" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Choo1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Choo, K. H., Gould, K. G., Rees, D. J. G., Brownlee, G. G.
|
|
<strong>Molecular cloning of the gene for human anti-haemophilic factor IX.</strong>
|
|
Nature 299: 178-180, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6287289/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6287289</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6287289" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/299178a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Choo1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Choo, K. H., Raphael, K., McAdam, W., Peterson, M. G.
|
|
<strong>Expression of active human blood clotting factor IX in transgenic mice: use of a cDNA with complete mRNA sequence.</strong>
|
|
Nucleic Acids Res. 15: 871-884, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3029708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3029708</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3029708" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/nar/15.3.871" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Chu1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chu, K., Wu, S.-M., Stanley, T., Stafford, D. W., High, K. A.
|
|
<strong>A mutation in the propeptide of factor IX leads to warfarin sensitivity by a novel mechanism.</strong>
|
|
J. Clin. Invest. 98: 1619-1625, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8833911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8833911</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8833911" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI118956" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="47" class="mim-anchor"></a>
|
|
<a id="Cooper1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cooper, D. N., Krawczak, M.
|
|
<strong>The mutational spectrum of single base-pair substitutions causing human genetic disease: patterns and predictions.</strong>
|
|
Hum. Genet. 85: 55-74, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2192981/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2192981</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2192981" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00276326" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="48" class="mim-anchor"></a>
|
|
<a id="Costa2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Costa, J.-M., Vidaud, D., Laurendeau, I., Vidaud, M., Fressinaud, E., Moisan, J.-P., David, A., Meyer, D., Lavergne, J.-M.
|
|
<strong>Somatic mosaicism and compound heterozygosity in female hemophilia B.</strong>
|
|
Blood 96: 1585-1587, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10942410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10942410</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10942410" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="49" class="mim-anchor"></a>
|
|
<a id="Crossley1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Crossley, M., Brownlee, G. G.
|
|
<strong>Disruption of a C/EBP binding site in the factor IX promoter is associated with haemophilia B.</strong>
|
|
Nature 345: 444-446, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2342576/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2342576</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2342576" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/345444a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="50" class="mim-anchor"></a>
|
|
<a id="Crossley1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Crossley, M., Ludwig, M., Stowell, K. M., De Vos, P., Olek, K., Brownlee, G. G.
|
|
<strong>Recovery from hemophilia B Leyden: an androgen-responsive element in the factor IX promoter.</strong>
|
|
Science 257: 377-379, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1631558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1631558</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1631558" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1631558" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="51" class="mim-anchor"></a>
|
|
<a id="Crossley1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Crossley, M., Winship, P. R., Austen, D. E. G., Rizza, C. R., Brownlee, G. G.
|
|
<strong>A less severe form of haemophilia B Leyden.</strong>
|
|
Nucleic Acids Res. 18: 4633, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2388855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2388855</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2388855" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/nar/18.15.4633" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="52" class="mim-anchor"></a>
|
|
<a id="Crossley1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Crossley, P. M., Winship, P. R., Black, A., Rizza, C. R., Brownlee, G. G.
|
|
<strong>Unusual case of haemophilia B. (Letter)</strong>
|
|
Lancet 333: 960 only, 1989. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2565449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2565449</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2565449" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0140-6736(89)92540-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="53" class="mim-anchor"></a>
|
|
<a id="Cutler2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cutler, J. A., Mitchell, M. J., Smith, M. P., Savidge, G. F.
|
|
<strong>Germline mosaicism resulting in the transmission of severe hemophilia B from a grandfather with a mild deficiency.</strong>
|
|
Am. J. Med. Genet. 129A: 13-15, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15266608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15266608</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15266608" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.30162" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="54" class="mim-anchor"></a>
|
|
<a id="Davie1975" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Davie, E. W., Fujikawa, K.
|
|
<strong>Basic mechanisms in blood coagulation.</strong>
|
|
Ann. Rev. Biochem. 44: 799-829, 1975.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/237463/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">237463</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=237463" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1146/annurev.bi.44.070175.004055" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="55" class="mim-anchor"></a>
|
|
<a id="Davis1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Davis, L. M., McGraw, R. A., Graham, J. B., Roberts, H. R., Stafford, D. W.
|
|
<strong>Identification of the genetic defect in factor IX (Alabama): DNA sequence analysis reveals a gly substitution for asp(46). (Abstract)</strong>
|
|
Blood 64 (suppl.): 262a, 1984.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="56" class="mim-anchor"></a>
|
|
<a id="Davis1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Davis, L. M., McGraw, R. A., Ware, J. L., Roberts, H. R., Stafford, D. W.
|
|
<strong>Factor IX (Alabama): a point mutation in a clotting protein results in hemophilia B.</strong>
|
|
Blood 69: 140-143, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3790720/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3790720</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3790720" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="57" class="mim-anchor"></a>
|
|
<a id="Denton1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Denton, P. H., Fowlkes, D. M., Lord, S. T., Reisner, H. M.
|
|
<strong>Hemophilia B Durham: a mutation in the first EGF-like domain of factor IX that is characterized by polymerase chain reaction.</strong>
|
|
Blood 72: 1407-1411, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3262389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3262389</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3262389" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="58" class="mim-anchor"></a>
|
|
<a id="Diuguid1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Diuguid, D. L., Rabiet, M. J., Furie, B. C., Liebman, H. A., Furie, B.
|
|
<strong>Molecular basis of hemophilia B: a defective enzyme due to an unprocessed propeptide is caused by a point mutation in the factor IX precursor.</strong>
|
|
Proc. Nat. Acad. Sci. 83: 5803-5807, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3461460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3461460</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3461460" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.83.16.5803" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="59" class="mim-anchor"></a>
|
|
<a id="Drayna1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Drayna, D., Davies, K., Hartley, D., Mandel, J.-L., Camerino, G., Williamson, R., White, R.
|
|
<strong>Genetic mapping of the human X chromosome by using restriction fragment length polymorphisms.</strong>
|
|
Proc. Nat. Acad. Sci. 81: 2836-2839, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6326147/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6326147</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6326147" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.81.9.2836" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="60" class="mim-anchor"></a>
|
|
<a id="Drost2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Drost, J. B., Scaringe, W. A., Jaloma-Cruz, A. R., Li, X., Ossa, D. F., Kasper, C. K., Sommer, S. S.
|
|
<strong>Novel hotspot detector software reveals a non-CpG hotspot of germline mutation in the factor IX gene (F9) in Latin Americans.</strong>
|
|
Hum. Mutat. 16: 203-210, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10980527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10980527</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10980527" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/1098-1004(200009)16:3<203::AID-HUMU3>3.0.CO;2-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="61" class="mim-anchor"></a>
|
|
<a id="Fahner1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fahner, J. B., Salier, J. P., Landa, L., Hirosawa, S., Lovrien, E. W., Kurachi, K.
|
|
<strong>Defective promoter structure in a human factor IX-Leyden. (Abstract)</strong>
|
|
Blood 72: 295A, 1988.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="62" class="mim-anchor"></a>
|
|
<a id="Fujikawa1974" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fujikawa, K., Coan, M. H., Enfield, D. L., Titani, K., Ericsson, L. H., Davie, E. W.
|
|
<strong>A comparison of bovine prothrombin, factor IX (Christmas factor), and factor X (Stuart factor).</strong>
|
|
Proc. Nat. Acad. Sci. 71: 427-430, 1974.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4205592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4205592</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4205592" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.71.2.427" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="63" class="mim-anchor"></a>
|
|
<a id="Geddes1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Geddes, V. A., Le Bonniec, B. F., Louie, G. V., Brayer, G. D., Thompson, A. R., MacGillivray, R. T. A.
|
|
<strong>A moderate form of hemophilia B is caused by a novel mutation in the protease domain of factor IX(Vancouver).</strong>
|
|
J. Biol. Chem. 264: 4689-4697, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2494175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2494175</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2494175" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="64" class="mim-anchor"></a>
|
|
<a id="Geddes1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Geddes, V. A., Louie, G. V., Brayer, G. D., MacGillivray, R. T. A.
|
|
<strong>Molecular basis of hemophilia B: identification of the defect in factor IX Vancouver. (Abstract)</strong>
|
|
Thromb. Haemost. 58 (suppl.): 294, 1987.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="65" class="mim-anchor"></a>
|
|
<a id="Giangrande2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giangrande, P. L. F.
|
|
<strong>Historical review: six characters in search of an author: the history of the nomenclature of coagulation factors.</strong>
|
|
Brit. J. Haemat. 121: 703-712, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12780784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12780784</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12780784" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1365-2141.2003.04333.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="66" class="mim-anchor"></a>
|
|
<a id="Giannelli1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Anagnostopoulos, T., Green, P. M.
|
|
<strong>Mutation rates in humans. II. Sporadic mutation-specific rates and rate of detrimental human mutations inferred from hemophilia B.</strong>
|
|
Am. J. Hum. Genet. 65: 1580-1587, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10577911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10577911</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10577911" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302652" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="67" class="mim-anchor"></a>
|
|
<a id="Giannelli1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Choo, K. H., Rees, D. J. G., Boyd, Y., Rizza, C. R., Brownlee, G. G.
|
|
<strong>Gene deletions in patients with haemophilia B and anti-factor IX antibodies.</strong>
|
|
Nature 303: 181-182, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6843667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6843667</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6843667" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/303181a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="68" class="mim-anchor"></a>
|
|
<a id="Giannelli1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Green, P. M., High, K. A., Sommer, S., Lillicrap, D. P., Ludwig, M., Olek, K., Reitsma, P. H., Goossens, M., Yoshioka, A., Brownlee, G. G.
|
|
<strong>Haemophilia B: database of point mutations and short additions and deletions--third edition, 1992.</strong>
|
|
Nucleic Acids Res. 20: 2027-2063, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1598234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1598234</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1598234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/nar/20.suppl.2027" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="69" class="mim-anchor"></a>
|
|
<a id="Giannelli1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Green, P. M., High, K. A., Sommer, S., Poon, M.-C., Ludwig, M., Schwaab, R., Reitsma, P. H., Goossens, M., Yoshioka, A., Brownlee, G. G.
|
|
<strong>Haemophilia B: database of point mutations and short additions and deletions--fourth edition, 1993.</strong>
|
|
Nucleic Acids Res. 21: 3075-3087, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8392713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8392713</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8392713" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/nar/21.13.3075" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="70" class="mim-anchor"></a>
|
|
<a id="Giannelli1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Green, P. M., Sommer, S. S., Poon, M.-C., Ludwig, M., Schwaab, R., Reitsma, P. H., Goossens, M., Yoshioka, A., Brownlee, G. G.
|
|
<strong>Haemophilia B (sixth edition): a database of point mutations and short additions and deletions.</strong>
|
|
Nucleic Acids Res. 24: 103-118, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8594556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8594556</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8594556" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/nar/24.1.103" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="71" class="mim-anchor"></a>
|
|
<a id="Giannelli1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Green, P. M., Sommer, S. S., Poon, M.-C., Ludwig, M., Schwaab, R., Reitsma, P. H., Goossens, M., Yoshioka, A., Figueiredo, M. S., Brownlee, G. G.
|
|
<strong>Haemophilia B: database of point mutations and short additions and deletions, 7th edition.</strong>
|
|
Nucleic Acids Res. 25: 133-135, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9016521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9016521</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9016521" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/nar/25.1.133" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="72" class="mim-anchor"></a>
|
|
<a id="Graham1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Graham, J. B., Lubahn, D. B., Lord, S. T., Kirshtein, J., Nilsson, I. M., Wallmark, A., Ljung, R., Frazier, L. D., Ware, J. L., Lin, S. W., Stafford, D. W., Bosco, J.
|
|
<strong>The Malmo polymorphism of coagulation factor IX, an immunologic polymorphism due to dimorphism of residue 148 that is in linkage disequilibrium with two other F.IX polymorphisms.</strong>
|
|
Am. J. Hum. Genet. 42: 573-580, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2450455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2450455</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2450455" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="73" class="mim-anchor"></a>
|
|
<a id="Graham1962" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Graham, J. B., Tarleton, H. L., Race, R. R., Sanger, R.
|
|
<strong>A human double cross-over.</strong>
|
|
Nature 195: 834, 1962.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13901025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13901025</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13901025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/195834a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="74" class="mim-anchor"></a>
|
|
<a id="Gray1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gray, M. W., Winship, P. R.
|
|
<strong>CpG polymorphisms and haemophilia B. (Letter)</strong>
|
|
Lancet 334: 502-503, 1989. Note: Originally Volume 2.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2570208/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2570208</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2570208" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0140-6736(89)92111-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="75" class="mim-anchor"></a>
|
|
<a id="Green1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Green, P. M., Bentley, D. R., Mibashan, R. S., Nilsson, I. M., Giannelli, F.
|
|
<strong>Molecular pathology of haemophilia B.</strong>
|
|
EMBO J. 8: 1067-1072, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2743975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2743975</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2743975" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/j.1460-2075.1989.tb03474.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="76" class="mim-anchor"></a>
|
|
<a id="Green1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Green, P. M., Mitchell, V. E., McGraw, A., Goldman, E., Giannelli, F.
|
|
<strong>Haemophilia B caused by a missense mutation in the prepeptide sequence of factor IX.</strong>
|
|
Hum. Mutat. 2: 103-107, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8318985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8318985</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8318985" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.1380020207" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="77" class="mim-anchor"></a>
|
|
<a id="Green1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
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.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1768766/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1768766</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1768766" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/00001721-199108000-00007" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="78" class="mim-anchor"></a>
|
|
<a id="Green1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Green, P. M., Montandon, A. J., Ljung, R., Nilsson, I. M., Giannelli, F.
|
|
<strong>Haplotype analysis of identical factor IX mutants using PCR.</strong>
|
|
Thromb. Haemost. 67: 66-69, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1615486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1615486</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1615486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="79" class="mim-anchor"></a>
|
|
<a id="Green1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Green, P. M., Saad, S., Lewis, C. M., Giannelli, F.
|
|
<strong>Mutation rates in humans. I. Overall and sex-specific rates obtained from a population study of hemophilia B.</strong>
|
|
Am. J. Hum. Genet. 65: 1572-1579, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10577910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10577910</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10577910" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302651" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="80" class="mim-anchor"></a>
|
|
<a id="Gu1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gu, W., Brooks, M., Catalfamo, J., Ray, J., Ray, K.
|
|
<strong>Two distinct mutations cause severe hemophilia B in two unrelated canine pedigrees.</strong>
|
|
Thromb. Haemost. 82: 1270-1275, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10544912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10544912</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10544912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="81" class="mim-anchor"></a>
|
|
<a id="Hassan1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hassan, H. J., Leonardi, A., Guerriero, R., Chelucci, C., Cianetti, L., Ciavarella, N., Ranieri, P., Pilolli, D., Peschle, C.
|
|
<strong>Hemophilia B with inhibitor: molecular analysis of the subtotal deletion of the factor IX gene.</strong>
|
|
Blood 66: 728-730, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2992643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2992643</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2992643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="82" class="mim-anchor"></a>
|
|
<a id="Hirosawa1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hirosawa, S., Fahner, J. B., Salier, J.-P., Wu, C.-T., Lovrien, E. W., Kurachi, K.
|
|
<strong>Structural and functional basis of the developmental regulation of human coagulation factor IX gene: factor IX Leyden.</strong>
|
|
Proc. Nat. Acad. Sci. 87: 4421-4425, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2352926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2352926</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2352926" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.87.12.4421" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="83" class="mim-anchor"></a>
|
|
<a id="Hougie1967" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hougie, C., Twomey, J. J.
|
|
<strong>Hemophilia B(M): a new type of factor-IX deficiency.</strong>
|
|
Lancet 289: 698-700, 1967. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4163943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4163943</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4163943" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0140-6736(67)92179-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="84" class="mim-anchor"></a>
|
|
<a id="Huang1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Huang, M.-N., Kasper, C. K., Roberts, H. R., Stafford, D. W., High, K. A.
|
|
<strong>Molecular defect in factor IX(Hilo), a hemophilia B(m) variant: arg-to-gln at the carboxyterminal cleavage site of the activation peptide.</strong>
|
|
Blood 73: 718-721, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2563663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2563663</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2563663" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="85" class="mim-anchor"></a>
|
|
<a id="Jagadeeswaran1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jagadeeswaran, P., Lavelle, D. E., Kaul, R., Mohandas, T., Warren, S. T.
|
|
<strong>Isolation and characterization of human factor IX cDNA: identification of Taq I polymorphism and regional assignment.</strong>
|
|
Somat. Cell Molec. Genet. 10: 465-473, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6089357/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6089357</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6089357" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF01534851" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="86" class="mim-anchor"></a>
|
|
<a id="Kasper1977" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kasper, C. K., Osterud, B., Minami, J. Y., Schonick, W., Rapaport, S. I.
|
|
<strong>Hemophilia B--characterization of genetic variants and detection of carriers.</strong>
|
|
Blood 50: 351-366, 1977.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/884315/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">884315</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=884315" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="87" class="mim-anchor"></a>
|
|
<a id="Kazazian1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kazazian, H. H., Jr.
|
|
<strong>An estimated frequency of endogenous insertional mutations in humans.</strong>
|
|
Nature Genet. 22: 130 only, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369250/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369250</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10369250" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/9638" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="88" class="mim-anchor"></a>
|
|
<a id="Ketterling1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ketterling, R. P., Bottema, C. D. K., Koeberl, D. D., Ii, S., Sommer, S. S.
|
|
<strong>T-296-to-M, a common mutation causing mild hemophilia B in the Amish and others: founder effect, variability in factor IX activity assays, and rapid carrier detection.</strong>
|
|
Hum. Genet. 87: 333-337, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1864609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1864609</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1864609" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00200915" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="89" class="mim-anchor"></a>
|
|
<a id="Ketterling1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ketterling, R. P., Vielhaber, E., Bottema, C. D. K., Schaid, D. J., Cohen, M. P., Sexauer, C. L., Sommer, S. S.
|
|
<strong>Germ-line origins of mutation in families with hemophilia B: the sex ratio varies with the type of mutation.</strong>
|
|
Am. J. Hum. Genet. 52: 152-166, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8434583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8434583</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8434583" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="90" class="mim-anchor"></a>
|
|
<a id="Ketterling1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ketterling, R. P., Vielhaber, E. L., Lind, T. J., Thorland, E. C., Sommer, S. S.
|
|
<strong>The rates and patterns of deletions in the human factor IX gene.</strong>
|
|
Am. J. Hum. Genet. 54: 201-213, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8304338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8304338</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8304338" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="91" class="mim-anchor"></a>
|
|
<a id="Ketterling1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ketterling, R. P., Vielhaber, E., Sommer, S. S.
|
|
<strong>The rates of G:C-to-T:A and G:C-to-C:G transversions at CpG dinucleotides in the human factor IX gene.</strong>
|
|
Am. J. Hum. Genet. 54: 831-835, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8178822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8178822</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8178822" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="92" class="mim-anchor"></a>
|
|
<a id="Kling1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kling, S., Ljung, R., Sjorin, E., Montandon, J., Green, P., Giannelli, F., Nilsson, I. M.
|
|
<strong>Origin of mutation in sporadic cases of haemophilia-B.</strong>
|
|
Europ. J. Haemat. 48: 142-145, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1348478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1348478</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1348478" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1600-0609.1992.tb00585.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="93" class="mim-anchor"></a>
|
|
<a id="Koeberl1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Koeberl, D. D., Bottema, C. D. K., Buerstedde, J.-M., Sommer, S. S.
|
|
<strong>Functionally important regions of the factor IX gene have a low rate of polymorphism and a high rate of mutation in the dinucleotide CpG.</strong>
|
|
Am. J. Hum. Genet. 45: 448-457, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2773937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2773937</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2773937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="94" class="mim-anchor"></a>
|
|
<a id="Koeberl1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Koeberl, D. D., Bottema, C. D. K., Ketterling, R. P., Bridge, P. J., Lillicrap, D. P., Sommer, S. S.
|
|
<strong>Mutations causing hemophilia B: direct estimate of the underlying rates of spontaneous germ-line transitions, transversions, and deletions in a human gene.</strong>
|
|
Am. J. Hum. Genet. 47: 202-217, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2198809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2198809</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2198809" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="95" class="mim-anchor"></a>
|
|
<a id="Koeberl1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Koeberl, D. D., Bottema, C. D. K., Sarkar, G., Ketterling, R. P., Chen, S.-H., Sommer, S. S.
|
|
<strong>Recurrent nonsense mutations at arginine residues cause severe hemophilia B in unrelated hemophiliacs.</strong>
|
|
Hum. Genet. 84: 387-390, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1969838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1969838</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1969838" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00195805" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="96" class="mim-anchor"></a>
|
|
<a id="Koeberl1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Koeberl, D. D., Bottema, C. D. K., Sommer, S. S.
|
|
<strong>Comparison of direct and indirect methods of carrier detection in an X-linked disease.</strong>
|
|
Am. J. Med. Genet. 35: 600-608, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1970704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1970704</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1970704" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1320350435" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="97" class="mim-anchor"></a>
|
|
<a id="Kundu1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kundu, R. K., Sangiorgi, F., Wu, L.-Y., Kurachi, K., Anderson, W. F., Maxson, R., Gordon, E. M.
|
|
<strong>Targeted inactivation of the coagulation factor IX gene causes hemophilia B in mice.</strong>
|
|
Blood 92: 168-174, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9639513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9639513</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9639513" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="98" class="mim-anchor"></a>
|
|
<a id="Kurachi1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kurachi, K., Davie, E. W.
|
|
<strong>Isolation and characterization of a cDNA coding for human factor IX.</strong>
|
|
Proc. Nat. Acad. Sci. 79: 6461-6464, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6959130/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6959130</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6959130" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.79.21.6461" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="99" class="mim-anchor"></a>
|
|
<a id="Kurachi1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kurachi, S., Deyashiki, Y., Takeshita, J., Kurachi, K.
|
|
<strong>Genetic mechanisms of age regulation of human blood coagulation factor IX.</strong>
|
|
Science 285: 739-743, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10426997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10426997</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10426997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.285.5428.739" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="100" class="mim-anchor"></a>
|
|
<a id="Kurachi2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kurachi, S., Huo, J. S., Ameri, A., Zhang, K., Yoshizawa, A. C., Kurachi, K.
|
|
<strong>An age-related homeostasis mechanism is essential for spontaneous amelioration of hemophilia B Leyden.</strong>
|
|
Proc. Nat. Acad. Sci. 106: 7921-7926, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19416882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19416882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19416882[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19416882" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0902191106" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="101" class="mim-anchor"></a>
|
|
<a id="Lefkowitz1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lefkowitz, J. B., Monroe, D. M., Kasper, C. K., Roberts, H. R.
|
|
<strong>Comparison of the behavior of normal factor IX and the factor IX BM variant Hilo in the prothrombin time test using tissue factors from bovine, human, and rabbit sources.</strong>
|
|
Am. J. Hemat. 43: 177-182, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8352232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8352232</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8352232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajh.2830430304" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="102" class="mim-anchor"></a>
|
|
<a id="Li2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Li, X., Scaringe, W. A., Hill, K. A., Roberts, S., Mengos, A., Careri, D., Pinto, M. T., Kasper, C. K., Sommer, S. S.
|
|
<strong>Frequency of recent retrotransposition events in the human factor IX gene.</strong>
|
|
Hum. Mutat. 17: 511-519, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11385709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11385709</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11385709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.1134" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="103" class="mim-anchor"></a>
|
|
<a id="Liddell1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Liddell, M. B., Peake, I. R., Taylor, S. A. M., Lillicrap, D. P., Giddings, J. C., Bloom, A. L.
|
|
<strong>Factor IX Cardiff: a variant factor IX protein that shows abnormal activation is caused by an arginine to cysteine substitution at position 145.</strong>
|
|
Brit. J. Haemat. 72: 556-560, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2775660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2775660</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2775660" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1989.tb04323.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="104" class="mim-anchor"></a>
|
|
<a id="Liebman1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Liebman, H. A., Limentani, S. A., Furie, B. C., Furie, B.
|
|
<strong>Immunoaffinity purification of factor IX (Christmas factor) by using conformation-specific antibodies directed against the factor IX-metal complex.</strong>
|
|
Proc. Nat. Acad. Sci. 82: 3879-3883, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2408269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2408269</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2408269" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.82.11.3879" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="105" class="mim-anchor"></a>
|
|
<a id="Little1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Little, R. D., Pilia, G., Johnson, S., D'Urso, M., Schlessinger, D.
|
|
<strong>Yeast artificial chromosomes spanning 8 megabases and 10-15 centimorgans of human cytogenetic band Xq26.</strong>
|
|
Proc. Nat. Acad. Sci. 89: 177-181, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1729687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1729687</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1729687" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.89.1.177" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="106" class="mim-anchor"></a>
|
|
<a id="Ljung2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ljung, R., Petrini, P., Tengborn, L., Sjorin, E.
|
|
<strong>Haemophilia B mutations in Sweden: a population-based study of mutational heterogeneity.</strong>
|
|
Brit. J. Haemat. 113: 81-86, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11328285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11328285</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11328285" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1365-2141.2001.02759.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="107" class="mim-anchor"></a>
|
|
<a id="Lozier1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lozier, B. N., Stanfield-Oakley, S. A., High, K. A.
|
|
<strong>Factor IX New London: a point mutation causing hemophilia B. (Abstract)</strong>
|
|
Thromb. Haemost. 62: 162, 1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="108" class="mim-anchor"></a>
|
|
<a id="Ludwig1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ludwig, M., Sabharwal, A. K., Brackmann, H. H., Olek, K., Smith, K. J., Birktoft, J. J., Bajaj, S. P.
|
|
<strong>Hemophilia B caused by five different nondeletion mutations in the protease domain of factor IX.</strong>
|
|
Blood 79: 1225-1232, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1346975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1346975</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1346975" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="109" class="mim-anchor"></a>
|
|
<a id="Ludwig1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ludwig, M., Schwaab, R., Eigel, A., Horst, J., Egli, H., Brackmann, H.-H., Olek, K.
|
|
<strong>Identification of a single nucleotide C-to-T transition and five different deletions in patients with severe hemophilia B.</strong>
|
|
Am. J. Hum. Genet. 45: 115-122, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2741941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2741941</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2741941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="110" class="mim-anchor"></a>
|
|
<a id="Mandalaki1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mandalaki, T., Louizou, C., Dimitriadou, C., Briet, E.
|
|
<strong>Haemophilia B Leyden in Greece.</strong>
|
|
Thromb. Haemost. 56: 340-342, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3563965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3563965</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3563965" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="111" class="mim-anchor"></a>
|
|
<a id="Matsushita1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matsushita, T., Tanimoto, M., Yamamoto, K., Sugiura, I., Hamaguchi, M., Takamatsu, J., Saito, H.
|
|
<strong>Nucleotide sequence analysis of hemophilia B with the inhibitor phenotype. (Abstract)</strong>
|
|
Blood 74: 251A, 1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="112" class="mim-anchor"></a>
|
|
<a id="Mattei1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mattei, M. G., Baeteman, M. A., Heilig, R., Oberle, I., Davies, K., Mandel, J. L., Mattei, J. F.
|
|
<strong>Localization by in situ hybridization of the coagulation factor IX gene and of two polymorphic DNA probes with respect to the fragile X site.</strong>
|
|
Hum. Genet. 69: 327-331, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2985491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2985491</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2985491" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00291650" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="113" class="mim-anchor"></a>
|
|
<a id="Matthews1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matthews, R. J., Anson, D. S., Peake, I. R., Bloom, A. L.
|
|
<strong>Heterogeneity of the factor IX locus in nine hemophilia B inhibitor patients.</strong>
|
|
J. Clin. Invest. 79: 746-753, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3029178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3029178</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3029178" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI112880" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="114" class="mim-anchor"></a>
|
|
<a id="Matthews1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matthews, R. J., Peake, I. R., Bloom, A. L., Anson, D. S.
|
|
<strong>Carrier detection through the use of abnormal deletion junction fragments in a case of haemophilia B involving complete deletion of the factor IX gene.</strong>
|
|
J. Med. Genet. 25: 779-780, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2907054/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2907054</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2907054" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.25.11.779" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="115" class="mim-anchor"></a>
|
|
<a id="McCord1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McCord, D. M., Monroe, D. M., Smith, K. J., Roberts, H. R.
|
|
<strong>Characterization of the functional defect in factor IX Alabama: evidence for a conformational change due to high affinity calcium binding in the first epidermal growth factor domain.</strong>
|
|
J. Biol. Chem. 265: 10250-10254, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2355000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2355000</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2355000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="116" class="mim-anchor"></a>
|
|
<a id="McGraw1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McGraw, R. A., Davis, L. M., Noyes, C. M., Lundblad, R. L., Roberts, H. R., Graham, J. B., Stafford, D. W.
|
|
<strong>Evidence for a prevalent dimorphism in the activation peptide of human coagulation factor IX.</strong>
|
|
Proc. Nat. Acad. Sci. 82: 2847-2851, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3857619/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3857619</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3857619" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.82.9.2847" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="117" class="mim-anchor"></a>
|
|
<a id="Mikami1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mikami, S., Nishino, M., Nishimura, T., Fukui, H.
|
|
<strong>RFLPs of factor IX gene in Japanese haemophilia B families and gene deletion in two high-responder-inhibitor patients.</strong>
|
|
Jpn. J. Hum. Genet. 32: 21-31, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2886685/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2886685</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2886685" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF01876524" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="118" class="mim-anchor"></a>
|
|
<a id="Miyata1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Miyata, T., Sakai, T., Sugimoto, M., Naka, H., Yamamoto, K., Yoshioka, A., Fukui, H., Mitsui, K., Kamiya, K., Umeyama, H., Iwanaga, S.
|
|
<strong>Factor IX Amagasaki: a new mutation in the catalytic domain resulting in the loss of both coagulant and esterase activities.</strong>
|
|
Biochemistry 30: 11286-11291, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1958666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1958666</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1958666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1021/bi00111a014" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="119" class="mim-anchor"></a>
|
|
<a id="Montandon1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Montandon, A. J., Green, P. M., Bentley, D. R., Ljung, R., Nilsson, I. M., Giannelli, F.
|
|
<strong>Two factor IX mutations in the family of an isolated haemophilia B patient: direct carrier diagnosis by amplification mismatch detection (AMD).</strong>
|
|
Hum. Genet. 85: 200-204, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2370049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2370049</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2370049" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00193196" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="120" class="mim-anchor"></a>
|
|
<a id="Noyes1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Noyes, C. M., Griffith, M. J., Roberts, H. R., Lundblad, R. L.
|
|
<strong>Identification of the molecular defect in factor IX(Chapel Hill): substitution of histidine for arginine at position 145.</strong>
|
|
Proc. Nat. Acad. Sci. 80: 4200-4202, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6603618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6603618</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6603618" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.80.14.4200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="121" class="mim-anchor"></a>
|
|
<a id="Oldenburg2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Oldenburg, J., Kriz, K., Wuillemin, W. A., Maly, F. E., von Felten, A., Siegemund, A., Keeling, D. M., Baker, P., Chu, K., Konkle, B. A., Lammle, B., Albert, T.
|
|
<strong>Genetic predisposition to bleeding during oral anticoagulant therapy: evidence for common founder mutations (FIXVal-10 and FIXThr-10) and an independent CpG hotspot mutation (FIXThr-10).</strong>
|
|
Thromb. Haemost. 85: 454-457, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11307814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11307814</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11307814" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="122" class="mim-anchor"></a>
|
|
<a id="Oldenburg1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Oldenburg, J., Quenzel, E.-M., Harbrecht, U., Fregin, A., Kress, W., Muller, C. R., Hertefelder, H.-J., Schwaab, R., Brackmann, H.-H., Hanfland, P.
|
|
<strong>Missense mutations at ala-10 in the factor IX propeptide: an insignificant variant in normal life but a decisive cause of bleeding during oral anticoagulant therapy.</strong>
|
|
Brit. J. Haemat. 98: 240-244, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9233593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9233593</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9233593" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1365-2141.1997.2213036.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="123" class="mim-anchor"></a>
|
|
<a id="Peake1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Peake, I. R., Furlong, B. L., Bloom, A. L.
|
|
<strong>Carrier detection by direct gene analysis in a family with haemophilia B (factor IX deficiency).</strong>
|
|
Lancet 323: 242-243, 1984. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6142993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6142993</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6142993" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0140-6736(84)90123-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="124" class="mim-anchor"></a>
|
|
<a id="Peake1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Peake, I. R., Matthews, R. J., Bloom, A. L.
|
|
<strong>Haemophilia B Chicago: severe haemophilia B caused by two deletions and an inversion within the factor IX gene.</strong>
|
|
Brit. J. Haemat. 71 (suppl. 1): 1, 1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="125" class="mim-anchor"></a>
|
|
<a id="Pezeshkpoor2018" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pezeshkpoor, B., Czogalla, K. J., Caspers, M., Berkemeier, A.-C., Liphardt, K., Ghosh, S., Kellner, M., Ulrich, S., Pavlova, A., Oldenburg, J.
|
|
<strong>Variants in FIX propeptide associated with vitamin K antagonism hypersensitivity: functional analysis and additional data confirming the common founder mutations.</strong>
|
|
Ann. Hemat. 97: 1061-1069, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29450643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29450643</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29450643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s00277-018-3264-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="126" class="mim-anchor"></a>
|
|
<a id="Picketts1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Picketts, D. J., D'Souza, C., Bridge, P. J., Lillicrap, D.
|
|
<strong>An A to T transversion at position -5 of the factor IX promoter results in hemophilia B.</strong>
|
|
Genomics 12: 161-163, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1733855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1733855</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1733855" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(92)90421-n" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="127" class="mim-anchor"></a>
|
|
<a id="Picketts1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Picketts, D. J., Lillicrap, D. P., Mueller, C. R.
|
|
<strong>Synergy between transcription factors DBP and C/EBP compensates for a haemophilia B Leyden factor IX mutation.</strong>
|
|
Nature Genet. 3: 175-179, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8499951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8499951</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8499951" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0293-175" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="128" class="mim-anchor"></a>
|
|
<a id="Poort1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Poort, S. R., Briet, E., Bertina, R. M., Reitsma, P. H.
|
|
<strong>A Dutch pedigree with mild hemophilia B with a missense mutation in the first EGF domain [factor IX(Oud en Nieuw Gastel)].</strong>
|
|
Nucleic Acids Res. 17: 5869, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2762170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2762170</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2762170" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/nar/17.14.5869" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="129" class="mim-anchor"></a>
|
|
<a id="Rees1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rees, D. J. G., Rizza, C. R., Brownlee, G. G.
|
|
<strong>Haemophilia B caused by a point mutation in a donor splice junction of the human factor IX gene.</strong>
|
|
Nature 316: 643-645, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4033760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4033760</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4033760" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/316643a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="130" class="mim-anchor"></a>
|
|
<a id="Reijnen1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Reijnen, M. J., Sladek, F. M., Bertina, R. M., Reitsma, P. H.
|
|
<strong>Disruption of a binding site for hepatocyte nuclear factor 4 results in hemophilia B Leyden.</strong>
|
|
Proc. Nat. Acad. Sci. 89: 6300-6303, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1631121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1631121</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1631121" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.89.14.6300" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="131" class="mim-anchor"></a>
|
|
<a id="Reitsma1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Reitsma, P. H., Bertina, R. M., Ploos van Amstel, J. K., Riemens, A., Briet, E.
|
|
<strong>The putative factor IX gene promoter in hemophilia B Leyden.</strong>
|
|
Blood 72: 1074, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3416069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3416069</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3416069" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="132" class="mim-anchor"></a>
|
|
<a id="Reitsma1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Reitsma, P. H., Mandalaki, T., Kasper, C. K., Bertina, R. M., Briet, E.
|
|
<strong>Two novel point mutations correlate with an altered developmental expression of blood coagulation factor IX (hemophilia B Leyden phenotype).</strong>
|
|
Blood 73: 743-746, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2917196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2917196</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2917196" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="133" class="mim-anchor"></a>
|
|
<a id="Rogaev2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rogaev, E. I., Grigorenko, A. P., Faskhutdinova, G., Kittler, E. L. W., Moliaka, Y. K.
|
|
<strong>Genotype analysis identifies the cause of the 'Royal disease.'</strong>
|
|
Science 326: 817 only, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19815722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19815722</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19815722" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1180660" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="134" class="mim-anchor"></a>
|
|
<a id="Royle1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Royle, G., Van de Water, N. S., Berry, E., Ockelford, P. A., Browett, P. J.
|
|
<strong>Haemophilia B Leyden arising de novo by point mutation in the putative factor IX promoter region.</strong>
|
|
Brit. J. Haemat. 77: 191-194, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2004020/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2004020</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2004020" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1991.tb07976.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="135" class="mim-anchor"></a>
|
|
<a id="Rusconi2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rusconi, C. P., Scardino, E., Layzer, J., Pitoc, G. A., Ortel, T. L., Monroe, D., Sullenger, B. A.
|
|
<strong>RNA aptamers as reversible antagonists of coagulation factor IXa.</strong>
|
|
Nature 419: 90-94, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12214238/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12214238</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12214238" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature00963" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="136" class="mim-anchor"></a>
|
|
<a id="Sakai1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sakai, T., Yoshioka, A., Yamamoto, K., Niinomi, K., Fujimura, Y., Fukui, H., Miyata, T., Iwanaga, S.
|
|
<strong>Blood clotting factor IX Kashihara: amino acid substitution of valine-182 by phenylalanine.</strong>
|
|
J. Biochem. 105: 756-759, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2753873/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2753873</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2753873" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/oxfordjournals.jbchem.a122740" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="137" class="mim-anchor"></a>
|
|
<a id="Sarkar1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sarkar, G., Cassady, J. D., Pyeritz, R. E., Gilchrist, G. S., Sommer, S. S.
|
|
<strong>Isoleucine-397 is changed to threonine in two females with hemophilia B.</strong>
|
|
Nucleic Acids Res. 19: 1165, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1902289/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1902289</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1902289" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/nar/19.5.1165" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="138" class="mim-anchor"></a>
|
|
<a id="Schach1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schach, B. G., Yoshitake, S., Davie, E. W.
|
|
<strong>Hemophilia B (factor IX-Seattle 2) due to a single nucleotide deletion in the gene for factor IX.</strong>
|
|
J. Clin. Invest. 80: 1023-1028, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2821070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2821070</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2821070" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI113155" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="139" class="mim-anchor"></a>
|
|
<a id="Siguret1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Siguret, V., Amselem, S., Vidaud, M., Assouline, Z., Kerbiriou-Nabias, D., Pietu, G., Goossens, M., Larrieu, M. J., Bahnak, B., Meyer, D., Lavergne, J. M.
|
|
<strong>Identification of a CpG mutation in the coagulation factor-IX gene by analysis of amplified DNA sequences.</strong>
|
|
Brit. J. Haemat. 70: 411-416, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3219291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3219291</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3219291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1988.tb02509.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="140" class="mim-anchor"></a>
|
|
<a id="Simioni2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Simioni, P., Tormene, D., Tognin, G., Gavasso, S., Bulato, C., Iacobelli, N. P., Finn, J. D., Spiezia, L., Radu, C., Arruda, V. R.
|
|
<strong>X-linked thrombophilia with a mutant factor IX (factor IX Padua).</strong>
|
|
New Eng. J. Med. 361: 1671-1675, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19846852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19846852</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19846852" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMoa0904377" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="141" class="mim-anchor"></a>
|
|
<a id="Smith1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Smith, K. J.
|
|
<strong>Monoclonal antibodies to coagulation factor IX define a high-frequency polymorphism by immunoassays.</strong>
|
|
Am. J. Hum. Genet. 37: 668-679, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9556657/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9556657</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9556657" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="142" class="mim-anchor"></a>
|
|
<a id="Solera1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Solera, J., Magallon, M., Martin-Villar, J., Coloma, A.
|
|
<strong>Factor IX(Madrid 2): a deletion/insertion in factor IX gene which abolishes the sequence of the donor junction at the exon IV-intron d splice site.</strong>
|
|
Am. J. Hum. Genet. 50: 434-437, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1346483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1346483</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1346483" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="143" class="mim-anchor"></a>
|
|
<a id="Sommer1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sommer, S. S., Bowie, E. J. W., Ketterling, R. P., Bottema, C. D. K.
|
|
<strong>Missense mutations and the magnitude of functional deficit: the example of factor IX.</strong>
|
|
Hum. Genet. 89: 295-297, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1601420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1601420</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1601420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00220543" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="144" class="mim-anchor"></a>
|
|
<a id="Sommer1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sommer, S. S.
|
|
<strong>Does cancer kill the individual and save the species? (Letter)</strong>
|
|
Hum. Mutat. 3: 166-169, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8199598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8199598</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8199598" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.1380030214" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="145" class="mim-anchor"></a>
|
|
<a id="Spitzer1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Spitzer, S. G., Pendurthi, U. R., Kasper, C. K., Bajaj, S. P.
|
|
<strong>Molecular defect in factor IX (Bm Lake Elsinore): substitution of ala390 by val in the catalytic domain.</strong>
|
|
J. Biol. Chem. 263: 10545-10548, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3392024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3392024</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3392024" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="146" class="mim-anchor"></a>
|
|
<a id="Spitzer1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Spitzer, S. G., Warn-Cramer, B. J., Kasper, C. C., Pendurthi, U. R., Bajaj, S. P.
|
|
<strong>Mutations in the catalytic domain of factor IXa which prevent macromolecular catalysis. (Abstract)</strong>
|
|
Circulation 78 (suppl. II): 118, 1988.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="147" class="mim-anchor"></a>
|
|
<a id="Spitzer1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Spitzer, S., Katzman, D., Kasper, C., Bajaj, S. P.
|
|
<strong>Factor IX Hollywood: substitution of 55 pro-to-ala in the first EGF domain. (Abstract)</strong>
|
|
Thromb. Haemost. 62: 203, 1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="148" class="mim-anchor"></a>
|
|
<a id="Suehiro1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Suehiro, K., Kawabata, S., Miyata, T., Takeya, H., Takamatsu, J., Ogata, K., Kamiya, T., Saito, H., Niho, Y., Iwanaga, S.
|
|
<strong>Blood clotting factor IX B(M) Nagoya: substitution of arginine 180 by tryptophan and its activation by alpha-chymotrypsin and rat mast cell chymase.</strong>
|
|
J. Biol. Chem. 264: 21257-21265, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2592373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2592373</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2592373" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="149" class="mim-anchor"></a>
|
|
<a id="Suehiro1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Suehiro, K., Miyata, T., Takeya, H., Takamatsu, J., Saito, H., Murakawa, M., Okamura, T., Niho, Y., Iwanaga, S.
|
|
<strong>Blood clotting factor IX Nagoya 3: the molecular defect of zymogen activation caused by an arginine-145 to histidine substitution.</strong>
|
|
Thromb. Res. 60: 311-320, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2087690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2087690</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2087690" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0049-3848(90)90109-p" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="150" class="mim-anchor"></a>
|
|
<a id="Sugimoto1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sugimoto, M., Miyata, T., Kawabata, S., Yoshioka, A., Fukui, H., Iwanaga, S.
|
|
<strong>Factor IX Kawachinagano: impaired function of the Gla-domain caused by attached propeptide region due to substitution of arginine by glutamine at position -4.</strong>
|
|
Brit. J. Haemat. 72: 216-221, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2757966/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2757966</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2757966" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1989.tb07685.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="151" class="mim-anchor"></a>
|
|
<a id="Sugimoto1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sugimoto, M., Miyata, T., Kawabata, S., Yoshioka, A., Fukui, H., Takahashi, H., Iwanaga, S.
|
|
<strong>Blood clotting factor IX Niigata: substitution of alanine-390 by valine in the catalytic domain.</strong>
|
|
J. Biochem. 104: 878-880, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3243764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3243764</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3243764" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/oxfordjournals.jbchem.a122575" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="152" class="mim-anchor"></a>
|
|
<a id="Tanimoto1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tanimoto, M., Kojima, T., Kamiya, T., Takamatsu, J., Ogata, K., Obata, Y., Inagaki, M., Iizuka, A., Nagao, T., Kurachi, K., Saito, H.
|
|
<strong>DNA analysis of seven patients with hemophilia B who have anti-factor IX antibodies: relationship to clinical manifestations and evidence that the abnormal gene was inherited.</strong>
|
|
J. Lab. Clin. Med. 112: 307-313, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3411192/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3411192</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3411192" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
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|
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|
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|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="153" class="mim-anchor"></a>
|
|
<a id="Taylor1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Taylor, S. A. M., Deugau, K. V., Lillicrap, D. P.
|
|
<strong>Somatic mosaicism and female-to-female transmission in a kindred with hemophilia B (factor IX deficiency).</strong>
|
|
Proc. Nat. Acad. Sci. 88: 39-42, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1986380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1986380</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1986380" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.88.1.39" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="154" class="mim-anchor"></a>
|
|
<a id="Taylor1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Taylor, S. A. M., Duffin, J., Cameron, C., Teitel, J., Garvey, B., Lillicrap, D. P.
|
|
<strong>Characterization of the original Christmas disease mutation (cysteine 206-to-serine): from clinical recognition to molecular pathogenesis.</strong>
|
|
Thromb. Haemost. 67: 63-65, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1615485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1615485</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1615485" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
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|
|
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|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="155" class="mim-anchor"></a>
|
|
<a id="Taylor1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Taylor, S. A. M., Liddell, M. B., Peake, I. R., Bloom, A. L., Lillicrap, D. P.
|
|
<strong>A mutation adjacent to the beta cleavage site of factor IX (valine 182 to leucine) results in mild haemophilia B(m).</strong>
|
|
Brit. J. Haemat. 75: 217-221, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2372509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2372509</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2372509" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1990.tb02652.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="156" class="mim-anchor"></a>
|
|
<a id="Taylor1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Taylor, S. A. M., Liddell, M. B., Peake, I. R., Lillicrap, D. P.
|
|
<strong>Mutations affecting cleavage of the activation peptide of factor IX as a cause of hemophilia B. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 45: A223, 1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="157" class="mim-anchor"></a>
|
|
<a id="Taylor1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Taylor, S. A. M., Lillicrap, D. P., Blanchette, V., Giles, A. R., Holden, J. J. A., White, B. N.
|
|
<strong>A complete deletion of the factor IX gene and new TaqI variant in a hemophilia B kindred.</strong>
|
|
Hum. Genet. 79: 273-276, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2841226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2841226</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2841226" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00366250" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="158" class="mim-anchor"></a>
|
|
<a id="Thompson1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Thompson, A. R., Chen, S.-H., Brayer, G. D.
|
|
<strong>Severe hemophilia B due to a G to T transversion changing gly 309 to val and inhibiting active protease conformation by preventing ion pair formation. (Abstract)</strong>
|
|
Blood 74: 134A, 1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="159" class="mim-anchor"></a>
|
|
<a id="Thompson1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Thompson, A. R.
|
|
<strong>Alloantibodies in hemophilia B binding to multiple factor IX epitopes.</strong>
|
|
Thromb. Res. 46: 169-174, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2438804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2438804</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2438804" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0049-3848(87)90217-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="160" class="mim-anchor"></a>
|
|
<a id="Thompson1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Thompson, A. R.
|
|
<strong>Personal Communication.</strong>
|
|
Seattle, Wash. 11/1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="161" class="mim-anchor"></a>
|
|
<a id="Tsang1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tsang, T. C., Bentley, D. R., Mibashan, R. S., Giannelli, F.
|
|
<strong>A factor IX mutation, verified by direct genomic sequencing, causing haemophilia B by a novel mechanism.</strong>
|
|
EMBO J. 7: 3009-3015, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3181127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3181127</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3181127" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/j.1460-2075.1988.tb03164.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="162" class="mim-anchor"></a>
|
|
<a id="Usharani1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Usharani, P., Warn-Cramer, B. J., Kasper, C. K., Bajaj, S. P.
|
|
<strong>Characterization of three abnormal factor IX variants (Bm Lake Elsinore, Long Beach, and Los Angeles) of hemophilia-B: evidence for defects affecting the latent catalytic site.</strong>
|
|
J. Clin. Invest. 75: 76-83, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3965513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3965513</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3965513" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI111700" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="163" class="mim-anchor"></a>
|
|
<a id="Veltkamp1970" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Veltkamp, J. J., Meilof, J., Remmelts, H. G., Van der Vlerk, D., Loeliger, E. A.
|
|
<strong>Another genetic variant of haemophilia B: haemophilia B Leyden.</strong>
|
|
Scand. J. Haemat. 7: 82-90, 1970.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5450691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5450691</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5450691" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1600-0609.1970.tb01873.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="164" class="mim-anchor"></a>
|
|
<a id="Vidaud1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vidaud, D., Tartary, M., Costa, J.-M., Bahnak, B. R., Gispert-Sanchez, S., Fressinaud, E., Gazengel, C., Meyer, D., Goossens, M., Lavergne, J.-M., Vidaud, M.
|
|
<strong>Nucleotide substitutions at the -6 position in the promoter region of the factor IX gene result in different severity of hemophilia B Leyden: consequences for genetic counseling.</strong>
|
|
Hum. Genet. 91: 241-244, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8478007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8478007</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8478007" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00218264" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="165" class="mim-anchor"></a>
|
|
<a id="Vidaud1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vidaud, D., Vidaud, M., Bahnak, B. R., Siguret, V., Sanchez, S. G., Laurian, Y., Meyer, D., Goossens, M., Lavergne, J. M.
|
|
<strong>Haemophilia B due to a de novo insertion of a human-specific Alu subfamily member within the coding region of the factor IX gene.</strong>
|
|
Europ. J. Hum. Genet. 1: 30-36, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8069649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8069649</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8069649" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000472385" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="166" class="mim-anchor"></a>
|
|
<a id="Vidaud1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vidaud, M., Chabret, C., Gazengel, C., Grunebaum, L., Cazenave, J. P., Goossens, M.
|
|
<strong>A de novo intragenic deletion of the potential EGF domain of the factor IX gene in a family with severe hemophilia B.</strong>
|
|
Blood 68: 961-963, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2875754/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2875754</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2875754" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="167" class="mim-anchor"></a>
|
|
<a id="Vidaud1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vidaud, M., Vidaud, D., Siguret, V., Lavergne, J. M., Goossens, M.
|
|
<strong>Mutational insertion of an Alu sequence causes hemophilia B. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 45: A226, 1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="168" class="mim-anchor"></a>
|
|
<a id="Vogel1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vogel, F., Motulsky, A. G.
|
|
<strong>Population genetics. In: Vogel, F.; Motulsky, A. G.: Human Genetics.</strong>
|
|
Berlin: Springer (pub.) 1986. Pp. 433-511.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="169" class="mim-anchor"></a>
|
|
<a id="Wadelius1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wadelius, C., Blomback, M., Pettersson, U.
|
|
<strong>Molecular studies of haemophilia B in Sweden: identification of patients with total deletion of the factor IX gene and without inhibitory antibodies.</strong>
|
|
Hum. Genet. 81: 13-17, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2848757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2848757</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2848757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00283721" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="170" class="mim-anchor"></a>
|
|
<a id="Wall1967" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wall, R. L., McConnell, J., Moore, D., Macpherson, C. R., Marson, A.
|
|
<strong>Christmas disease, color-blindness and blood group Xg(a).</strong>
|
|
Am. J. Med. 43: 214-226, 1967.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5298508/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5298508</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5298508" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0002-9343(67)90166-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="171" class="mim-anchor"></a>
|
|
<a id="Wang1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wang, L., Zoppe, M., Hackeng, T. M., Griffin, J. H., Lee, K.-F., Verma, I. M.
|
|
<strong>A factor IX-deficient mouse model for hemophilia B gene therapy.</strong>
|
|
Proc. Nat. Acad. Sci. 94: 11563-11566, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9326649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9326649</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9326649[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9326649" 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.94.21.11563" target="_blank">Full Text</a>]
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</p>
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<a id="172" class="mim-anchor"></a>
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<a id="Wang1990" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
|
Wang, N. S., Zhang, M., Thompson, A. R., Chen, S.-H.
|
|
<strong>Factor IX(Chongqing): a new mutation in the calcium-binding domain of factor IX resulting in severe hemophilia B.</strong>
|
|
Thromb. Haemost. 63: 24-26, 1990.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2339358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2339358</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2339358" 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="173" class="mim-anchor"></a>
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<a id="Ware1988" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
|
Ware, J., Davis, L., Frazier, D., Bajaj, S. P., Stafford, D. W.
|
|
<strong>Genetic defect responsible for the dysfunctional protein: factor IX (Long Beach).</strong>
|
|
Blood 72: 820-822, 1988.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3401602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3401602</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3401602" 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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</div>
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</li>
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<li>
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<a id="174" class="mim-anchor"></a>
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<a id="Ware1989" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
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|
Ware, J., Diuguid, D. L., Liebman, H. A., Rabiet, M.-J., Kasper, C. K., Furie, B. C., Furie, B., Stafford, D. W.
|
|
<strong>Factor IX San Dimas: substitution of glutamine for arg(-4) in the propeptide leads to incomplete gamma-carboxylation and altered phospholipid binding properties.</strong>
|
|
J. Biol. Chem. 264: 11401-11406, 1989.
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|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2738071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2738071</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2738071" 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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</div>
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</li>
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<li>
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<a id="175" class="mim-anchor"></a>
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<a id="Wilkinson2002" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
|
Wilkinson, F. H., London, F. S., Walsh, P. N.
|
|
<strong>Residues 88-109 of factor IXa are important for assembly of the factor X activating complex.</strong>
|
|
J. Biol. Chem. 277: 5725-5733, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11726655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11726655</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11726655" 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/10.1074/jbc.M107027200" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="176" class="mim-anchor"></a>
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<a id="Winship1986" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
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Winship, P. R., Brownlee, G. G.
|
|
<strong>Diagnosis of haemophilia B carriers using intragenic oligonucleotide probes. (Letter)</strong>
|
|
Lancet 328: 218-219, 1986. Note: Originally Volume 2.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2873459/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2873459</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2873459" 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(86)92513-4" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="177" class="mim-anchor"></a>
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<a id="Winship1991" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Winship, P. R., Dragon, A. C.
|
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<strong>Identification of haemophilia B patients with mutations in the two calcium binding domains of factor IX: importance of a beta-OH asp64-to-asn change.</strong>
|
|
Brit. J. Haemat. 77: 102-109, 1991. Note: Erratum: Brit. J. Haemat. 77: 446 only, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1998585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1998585</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1998585" 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/10.1111/j.1365-2141.1991.tb07955.x" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="178" class="mim-anchor"></a>
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<a id="Winship1989" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Winship, P. R., Rees, D. J. G., Alkan, M.
|
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<strong>Detection of polymorphisms at cytosine phosphoguanidine dinucleotides and diagnosis of haemophilia B carriers.</strong>
|
|
Lancet 333: 631-634, 1989. Note: Originally Volume 1.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2564457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2564457</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2564457" 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(89)92141-7" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="179" class="mim-anchor"></a>
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<a id="Winship1989" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Winship, P. R.
|
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<strong>Characterisation of the molecular defect in haemophilia B patients using the polymerase chain reaction procedure. (Abstract)</strong>
|
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Thromb. Haemost. 62: 465, 1989.
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</p>
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</div>
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<li>
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<a id="180" class="mim-anchor"></a>
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<a id="Winship1990" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Winship, P. R.
|
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<strong>Haemophilia B caused by mutation of a potential thrombin cleavage site in factor IX.</strong>
|
|
Nucleic Acids Res. 18: 1310, 1990.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2320433/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2320433</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2320433" 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/18.5.1310" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="181" class="mim-anchor"></a>
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<a id="Yoshioka1986" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yoshioka, A., Ohkubo, Y., Nishimura, T., Tanaka, I., Fukui, H., Ogata, K., Kamiya, T., Takahashi, H.
|
|
<strong>Heterogeneity of factor IX BM: difference in cleavage sites by factor XIa and Ca(2+) in factor IX Kashihara, factor IX Nagoya and factor IX Niigata.</strong>
|
|
Thromb. Res. 42: 595-604, 1986.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3487139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3487139</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3487139" 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/10.1016/0049-3848(86)90338-5" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="182" class="mim-anchor"></a>
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<a id="Zhang1989" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhang, M., Chen, S.-H., Thompson, A. R., Lovrien, E., Scott, C. R.
|
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<strong>CG dinucleotides are 'hot spots' in the factor IX gene for point mutations: evidence from the study of 25 families with defined mutations causing hemophilia B. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 45: A231, 1989.
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</p>
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</div>
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</li>
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</ol>
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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="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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</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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Hilary J. Vernon - updated : 09/29/2020
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</span>
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</div>
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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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Ada Hamosh - updated : 12/29/2009<br>Cassandra L. Kniffin - updated : 11/25/2009<br>Cassandra L. Kniffin - updated : 11/10/2009<br>Cassandra L. Kniffin - updated : 10/24/2008
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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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<a id="creationDate" 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="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 : 10/9/2008
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</span>
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<div>
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<a id="editHistory" 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="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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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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carol : 01/07/2025
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 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 : 08/14/2023<br>carol : 09/30/2020<br>carol : 09/29/2020<br>carol : 07/24/2020<br>carol : 02/26/2018<br>alopez : 12/11/2017<br>carol : 10/09/2017<br>joanna : 08/04/2016<br>carol : 09/11/2013<br>carol : 11/12/2012<br>carol : 3/1/2012<br>carol : 2/29/2012<br>carol : 2/28/2012<br>carol : 7/6/2011<br>terry : 5/20/2011<br>carol : 4/7/2011<br>carol : 1/26/2011<br>carol : 10/12/2010<br>alopez : 1/5/2010<br>terry : 12/29/2009<br>wwang : 12/2/2009<br>terry : 12/1/2009<br>ckniffin : 11/25/2009<br>carol : 11/11/2009<br>ckniffin : 11/10/2009<br>terry : 6/5/2009<br>terry : 6/5/2009<br>terry : 6/3/2009<br>terry : 4/13/2009<br>terry : 4/9/2009<br>carol : 11/20/2008<br>terry : 11/19/2008<br>carol : 10/30/2008<br>ckniffin : 10/24/2008<br>carol : 10/21/2008<br>ckniffin : 10/15/2008
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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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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
|
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<strong>*</strong> 300746
|
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</span>
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</h3>
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</div>
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<div>
|
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<h3>
|
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<span class="mim-font">
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|
|
COAGULATION FACTOR IX; F9
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</span>
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</h3>
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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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<p>
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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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</p>
|
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</div>
|
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<div>
|
|
<h4>
|
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<span class="mim-font">
|
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FACTOR IX<br />
|
|
PLASMA THROMBOPLASTIN COMPONENT; PTC
|
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</span>
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</h4>
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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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<div>
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<p>
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: F9</em></strong>
|
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 1336117005;
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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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<p>
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<span class="mim-text-font">
|
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<strong>
|
|
<em>
|
|
Cytogenetic location: Xq27.1
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : X:139,530,739-139,563,459 </span>
|
|
</em>
|
|
</strong>
|
|
<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>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="4">
|
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<span class="mim-font">
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Xq27.1
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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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{Deep venous thrombosis, protection against}
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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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300807
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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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{Warfarin sensitivity}
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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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301052
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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
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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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Hemophilia B
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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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306900
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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 8, X-linked, due to factor IX defect
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
300807
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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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</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 F9 gene encodes coagulation factor IX, which circulates as an inactive zymogen until proteolytic release of its activation peptide allows it to assume the conformation of an active serine protease (Davie and Fujikawa, 1975). Its role in the blood coagulation cascade is to activate factor X (F10; 227600) through interactions with calcium, membrane phospholipids, and factor VIII (F8; 300841). Factor IX and factor X both consist of 2 polypeptide chains referred to as the L (light) and H (heavy) chains. The H chain bears a structural resemblance to the polypeptide chain of the pancreatic serine protease trypsin (PRSS1; 276000). The L chain is covalently linked to the H chain by a single disulfide bond (Fujikawa et al., 1974). </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>Kurachi and Davie (1982) isolated and characterized a cDNA coding for the human factor IX gene. The deduced 416-residue protein contains a 46-residue leader sequence that includes both a signal sequence and a pro-sequence for the mature protein that circulates in plasma. The amino-terminal region contains 12 glutamic acid residues that are converted to gamma-carboxyglutamic acid in the mature protein. The arginyl peptide bonds that are cleaved in the conversion of human factor IX to factor IXa by factor XIa (F11; 264900) were identified as Arg145-Ala146 and Arg180-Val181. The cleavage of these 2 internal peptide bonds results in the formation of a 35-residue activation peptide and factor IXa, a serine protease composed of a 145-residue light chain and a 236-residue heavy chain that are held together by a disulfide bond. The homology in the amino acid sequence between human and bovine factor IX was found to be 83%. </p><p>Choo et al. (1982) isolated clones corresponding to the human factor IX gene from a human cDNA library. The deduced human protein showed 78% homology with the bovine protein. </p><p>Jagadeeswaran et al. (1984) used the peptide sequence of bovine F9 to develop a probe to screen a human liver cDNA library. They identified a recombinant clone corresponding to 70% of the coding region of human factor IX. This F9 cDNA was used to probe restriction endonuclease digested polymorphism, as well as to verify that the haploid genome contains a single copy of the gene. </p><p>Anson et al. (1984) isolated clones corresponding to the full sequence of the human factor IX gene from a human liver cDNA library. The gene encodes a mature 415-residue protein. </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>Anson et al. (1984) determined that the F9 gene contains 8 exons and spans about 34 kb. Introns accounted for 92% of the gene length. Exons conformed roughly to previously designated protein regions but the catalytic region of the protein appeared to be coded by 2 separate exons, which differed from the arrangement in other characterized serine protease genes. </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">
|
|
<strong>Gene Function</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 IXa activates factor X as part of an intrinsic activating complex that also consists of factor VIIIa. Using several chimeric and mutant F9 proteins in coagulation assays, Wilkinson et al. (2002) determined that residues 88 to 109, excluding arg94, within the second epidermal growth factor-like domain of factor IX are important for phospholipid surface assembly of the factor X activating complex. </p><p>Rusconi et al. (2002) demonstrated that protein-binding oligonucleotides (aptamers) against coagulation factor IXa are potent anticoagulants. They also showed that oligonucleotides complementary to these aptamers could act as antidotes capable of efficiently reversing the activity of these new anticoagulants in plasma from healthy volunteers and from patients who cannot tolerate heparin. Rusconi et al. (2002) concluded that their strategy was generalizable for rationally designing a drug-antidote pair, thus opening the way for developing safer regulatable therapeutics. </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>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
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</span>
|
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</h4>
|
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</div>
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|
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<span class="mim-text-font">
|
|
<p>Camerino et al. (1983) used a factor IX gene probe to demonstrate close linkage to the locus for fragile X syndrome (300624) (17 nonrecombinants, 0 recombinants; lod = 5.12 at theta = 0.0). </p><p>Chance et al. (1983) assigned the human F9 gene to chromosome Xq27-qter using somatic cell hybridization. F9 was in a fragment of the X chromosome associated with no HPRT (308000) activity in the hybrid cell, suggesting that F9 is distal to HPRT. </p><p>Using a cDNA probe in the study of human-mouse hybrid cells, Camerino et al. (1984) mapped the F9 locus to Xq26-q27. Furthermore, they identified a TaqI polymorphism with allelic frequencies of about 0.71 and 0.29. By in situ hybridization and by study of rodent-human somatic cell hybrids with various aberrations of the human X, Boyd et al. (1984) assigned the factor IX locus to Xq26-qter. Jagadeeswaran et al. (1984) also mapped the F9 gene to Xq26-qter. </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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|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<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">
|
|
<p><strong><em>Hemophilia B</em></strong></p><p>
|
|
Using genomic DNA probes, Chen et al. (1985) identified a partial intragenic deletion in the F9 gene in 7 affected members of a family with severe hemophilia B (306900). </p><p>In affected members of a family with severe factor IX deficiency and no detectable factor IX protein, Taylor et al. (1988) identified a complete deletion of the F9 gene that extended at least 80 kb 3-prime of the gene. The proband did not have antibodies to factor IX, despite total deletion of the gene. </p><p>Matthews et al. (1988) discussed the family originally reported by Peake et al. (1984) as having an X-chromosome deletion of minimum size 114 kb that included the entire F9 gene. By isolation of further 3-prime flanking probes, they located the 3-prime breakpoint of the deletion to a position 145 kb 3-prime to the start of the F9 gene. Abnormal junction fragments detected at the breakpoint were used in the detection of carriers. </p><p>In a patient with severe hemophilia B, Siguret et al. (1988) found loss of the TaqI restriction site at the 5-prime end of exon 8 of the F9 gene. Using oligonucleotide probes and PCR-amplified DNA for sequencing of the affected region, the authors identified a C-to-T change in the catalytic domain of the protein, resulting in premature termination. The change resulted from a CpG mutation. </p><p>By use of PCR followed by sequencing, Bottema et al. (1989) identified mutations in the F9 gene (see, e.g., 300746.0051) in all 14 hemophilia B patients studied. Analysis for heterozygosity in at-risk female relatives was then done, either by sequencing the appropriate region or by detection of an altered restriction site.</p><p>Green et al. (1991) provided a list of point mutations that cause hemophilia B. Sommer et al. (1992) estimated that missense mutations cause only 59% of moderate and severe hemophilia B and that these mutations are almost always (95%) of independent origin (i.e., de novo mutations). In contrast, missense mutations were found in virtually all (97%) families with mild disease and only a minority of these (41%) were of independent origin. </p><p>Giannelli et al. (1993) reported on the findings in a database of 806 patients with hemophilia B in whom the defect in factor IX had been identified at the molecular level. A total of 379 independent mutations were described. The list included 234 different amino acid substitutions. There were 13 promoter mutations, 18 mutations in donor splice sites, 15 mutations in acceptor splice sites, and 4 mutations creating cryptic splice sites. In analyses of DNA from 290 families with hemophilia B (203 independent mutations), Ketterling et al. (1994) found 12 deletions more than 20 bp long. Eleven of these were more than 2 kb long and one was 1.1 kb. </p><p>Giannelli et al. (1996) described the sixth edition of their hemophilia B database of point mutations and short (less than 30 bp) additions and deletions. The 1,380 patient entries were ordered by the nucleotide number of their mutation. References to published mutations were given and the laboratories generating the data were indicated. Giannelli et al. (1997) described the seventh edition of their database; 1,535 patient entries were ordered by the nucleotide number of their mutation. When known, details were given on factor IX activity, factor IX antigen in the circulation, presence of inhibitor, and origin of mutation. </p><p>Ljung et al. (2001) surveyed a series comprising all 77 known families with hemophilia B in Sweden. The disorder was severe in 38, moderate in 10, and mild in 29. A total of 51 different mutations were found. Ten of the mutations, all C-to-T or G-to-A transitions, recurred in 1 to 6 additional families. Using haplotype analysis of 7 polymorphisms in the F9 gene, Ljung et al. (2001) found that the 77 families carried 65 unique, independent mutations. Of the 48 families with severe or moderate hemophilia, 23 (48%) had a sporadic case compared with 31 families of 78 (40%) in the whole series. Five of those 23 sporadic cases carried de novo mutations; 11 of 23 of the mothers were proven carriers; and in the remaining 7 families, it was not possible to determine carriership. </p><p><strong><em>X-Linked Thrombophilia due to Factor IX Defect</em></strong></p><p>
|
|
In an Italian man with deep venous thrombosis of the femoral-popliteal veins (THPH8; 300807), Simioni et al. (2009) identified a hemizygous mutation in the F9 gene (R338L; 300746.0112). Coagulation studies showed that he had normal levels of F9 antigen, but very high levels of F9 activity (776% of control values). </p><p><strong><em>Warfarin Sensitivity</em></strong></p><p>
|
|
In a 49-year-old patient who was found to have warfarin sensitivity, Chu et al. (1996) identified an A-10T mutation in the propeptide of the factor IX gene (A37T; 300746.0102). The mutation was found by direct sequence analysis of amplified genomic DNA from all 8 exons and exon-intron junctions of F9. </p><p>In 3 patients with warfarin sensitivity, Oldenburg et al. (1997) identified mutations in the F9 gene: A-10T in 1 patient and an A-10V mutation (A37V; 300746.0103) in the others. </p><p>Pezeshkpoor et al. (2018) identified the A37T mutation in the F9 gene in 11 patients with X-linked warfarin sensitivity, including 6 patients previously reported by Oldenburg et al. (2001), and the A37V mutation in 7 patients, including 5 patients previously reported by Oldenburg et al. (2001). Expression of F9 containing the A37T mutation or the A37V mutation in HEK293T cells resulted in a reduction in the FIX:C ratio and a reduced half maximal inhibitory concentration (IC50) for warfarin compared to HEK293T cells transfected with wildtype F9. This indicated a sensitivity to warfarin conferred by both mutations, with A37V conferring less warfarin sensitivity than A37T. </p><p>By haplotype analysis in 11 patients with the A37T mutation and 7 patients with the A37V mutation, Pezeshkpoor et al. (2018) found that both were founder mutations in the European population. They noted that 2 patients from the US with the A37T mutation (patients J and K in Oldenburg et al., 2001) shared a different haplotype than the 9 European patients with the A37T mutation, indicating an independent origin. </p><p><strong><em>Mechanism of Mutation Generation</em></strong></p><p>
|
|
Methylation of CpG dinucleotides constitutes an endogenous mechanism of mutation, which results from insufficient repair of the deamination product to 5-methyl cytosine (Ketterling et al., 1993). Among 22 patients with hemophilia B, Koeberl et al. (1989) found a high rate of mutation at CpG dinucleotides. Transitions of CpG accounted for 31% (5 out of 16) of distinct mutations and for 38% (5 out of 13) of single base changes. The authors used a method of genome amplification with transcript sequencing to perform direct sequencing on 8 regions of the F9 gene. </p><p>Cooper and Krawczak (1990) made an extensive survey of single basepair substitutions that cause various human genetic diseases and found that 32% were CG-to-TG or CG-to-CA transitions. This was a 12-fold increase over the frequency predicted from random expectation. They presented a computer model (MUTPRED) designed to predict the location of mutations within gene coding regions causing human genetic disease. The model predicted successfully the rank order of disease prevalence and/or mutation rates associated with various human autosomal dominant and X-linked recessive conditions. The mutational spectrum predicted for the F9 gene resembled closely that observed for point mutations causing hemophilia B. Cooper and Krawczak (1990) quoted from Edmund Spenser's 'The Faerie Queene' (circa 1609): '...mutability in them doth play her cruell cruell sports, to many men's decay.' </p><p>To study the nature of spontaneous mutation, Koeberl et al. (1990) sequenced 8 regions (a total of 2.46 kb) of likely functional significance in the F9 gene in 60 consecutive, unrelated patients with hemophilia B. From the pattern of mutations causing disease and from a knowledge of evolutionarily conserved amino acids, they reconstructed the underlying pattern of mutation and calculated the mutation rates per basepair per generation for transitions (G-A or C-T changes) as 27 x 10(-10), transversions (A-T, A-C, G-T, or G-C changes) as 4.1 x 10(-10), and deletions as 0.9 x 10(-10), for a total mutation rate of 32 x 10(-10). No insertions were observed in this sample. The proportion of transitions at non-CpG dinucleotides was raised 7-fold over that expected if 1 base substitution were as likely as another; at the dinucleotide CpG, transitions were found to be increased 24-fold relative to transitions at other sites. Mutations putatively affecting splicing accounted for at least 13% of mutations, indicating that the division of the gene into 8 exons represents a significant genetic cost to the organism. All the missense mutations occurred at evolutionarily conserved amino acids. </p><p>Bottema et al. (1990) found that in Asians (mostly Koreans), as in Caucasians, transitions dominate among F9 mutations, followed by transversions and microdeletions/insertions. On the basis of their data combined with previous data, the authors concluded that more than two-thirds of the missense mutations that can occur at nonconserved amino acids do not cause hemophilia B. </p><p>In their series of patients with hemophilia B, Chen et al. (1991) found that 23 (45%) of 51 substitutions in the F9 gene occurred as C-to-T or G-to-A transitions at 11 sites within CpG dinucleotides. More than 1 family had identical defects for 6 of the CpG mutations. At 4 of these sites, most patients had different haplotypes compatible with distinct mutations. Non-CpG mutations occurred throughout the coding regions with only 1 mutation in more than one family. </p><p>Bottema et al. (1991) identified 95 independent missense mutations in the F9 gene resulting in hemophilia B; 94 of these occurred at amino acids that are evolutionarily conserved in mammalian factor IX sequences. They pointed out that the likelihood of a missense mutation causing hemophilia B depends on whether the residue is also conserved in the factor IX-related proteases: factor VII, factor X (F10; see 227600), and protein C (PROC; 612283). They found that most of the possible missense mutations in residues conserved in factor IX in all the related proteases resulted in disease, whereas missense mutations not conserved in the related proteases were 6-fold less likely to cause disease. Missense mutations at nonconserved residues were 33-fold less likely to cause disease. Bottema et al. (1991) concluded that many of the residues in factor IX are spacers; that is, the main chains are presumably necessary to keep other amino acid interactions in register, but the nature of the side chain is unimportant. </p><p>Bottema et al. (1991) found that transversions at CpG dinucleotides are elevated an estimated 7.7-fold relative to other transversions. On the other hand, the mutation rates at non-CpG dinucleotides are relatively uniform. They suggested that the high rate of CpG transversions accounts for the fact that the F9 gene has a G+C content of approximately 40%. </p><p>Bottema et al. (1993) gave an updated estimate on mutations at CpG dinucleotides in the F9 gene. Of the independent transitions they had delineated in a consecutive sample of 290 families with hemophilia B, 42% occurred at CpG sites. Overall, CpG mutations represented 36% of the point mutations and 30% of all mutations in their sample. An observed 20-fold enhancement for mutation at CpG sites with frequent mutations reflected, they suggested, the situation at fully or mostly methylated sites. </p><p>Based particularly on his extensive experience with mutation analysis in hemophilia B, Sommer (1994) proposed an ingenious hypothesis concerning the role of cancer in mediating evolutionary selection for a constant rate of germline mutation. The hypothesis was based on data suggesting that most germline mutations are due to endogenous processes such as methylation of DNA at CpG dinucleotides. Furthermore, despite differences in environment, diet, lifestyle, and occupational exposure, the pattern of factor IX mutations is remarkably similar in populations all over the world. Also despite the many differences in the environment of modern day humans, the biases in the dinucleotide mutation rates during the past 150 years are compatible with the ancient pattern that fashioned the G+C content of 40%. Assuming that somatic mutation leading to early-onset cancer occurs at rates similar to the germline mutation rate, then these cancers that interfere with reproduction might cap the germline mutation rate. Some have pointed out that cancer is a sensitive mediator of negative selection because the multiple mutations required for carcinogenesis can amplify the effects of small increases in the mutation rate. A certain rate of mutation is required to generate sufficient variation for adaptation during evolutionary time. Sexual reproduction and recombination serves to enhance variation, but ultimately new germline mutation is required to replenish variant alleles lost secondary to negative selection, genetic drift, and population bottlenecks. Unfortunately, the requisite mutation rate carries a terrible price, since for each advantageous mutation, there are many disadvantageous ones. Consequently, the optimal mutation rate should be at a level just sufficient to maintain the variation needed for adaptation. Mechanisms for negative selection are needed to keep the mutation rate in check. Cancer may serve that role. </p><p>Of 727 independent mutations (0.28%) of the F9 gene in patients with hemophilia B, Li et al. (2001) observed only 2 germline retrotransposition mutations: a 279-bp insertion in exon 8 originating from an Alu family of short interspersed elements not previously known to be active, and a 463-bp insertion in exon e of a LINE-1 element originating in a maternal grandmother. The authors stated that if the rates of recent germline mutation in F9 are typical of the genome, a retrotransposition event is estimated to occur somewhere in the genome of about 1 in every 17 children born. Analysis of other estimates for retrotransposition frequency and overall mutation rates suggested that the actual rate of retrotransposition is likely to be in the range of 1 in every 2.4 to 1 in every 28 live births. Kazazian (1999) analyzed the frequency of retrotransposition events involving 860 genes. These included retrotranspositions identified in X-linked and severe autosomal dominant disorders, likely to have occurred within the last 150 years, and autosomal recessive disorders in which the mutations may have occurred 10,000 or more years ago. </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">
|
|
<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>Hirosawa et al. (1990) noted that all 5 families with hemophilia B Leyden, in which a severe bleeding disorder in childhood becomes mild after puberty, had mutations in an approximately 40-kb region in the 5-prime untranslated region of F9, which the authors referred to as the Leyden-specific region (LSR). Base changes at nucleotide -20 (300746.0001) as well as at nucleotide -6 (300746.0002) and deletions of the 3-prime half of the LS region reduced expression of the factor IX gene to about 15-31% that of normal controls, as assessed in a cultured cell (HepG2) expression system. Androgen significantly increased the transcriptional activities of both mutant and normal factor IX genes in a concentration-dependent manner. The findings suggested that a mutations in this region could lead to a switch from constitutive to steroid hormone-dependent gene expression. </p><p>Kurachi et al. (2009) stated that the LSR has been narrowed to an approximately 50-bp region between nucleotides -34 and +19. Crossley and Brownlee (1990) identified a binding site for the CCAAT/enhancer binding protein (C/EBP, CEBPA; 116897) extending from +1 to +18 in the F9 gene, which is capable of transactivating a factor IX promoter. Hepatocyte nuclear factor-4 (HNF4; 600281), a member of the steroid hormone receptor superfamily of transcription factors, also binds to nucleotides -26 to -20 of the promoter region in the F9 gene (Reijnen et al., 1992). </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>Animal Model</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>Kundu et al. (1998) generated a transgenic mouse model of hemophilia B by targeted disruption of the murine F9 gene. The tail bleeding time of hemizygous male mice was markedly prolonged compared with those of normal and carrier female littermates. Seven of 19 affected male mice died of exsanguination after tail snipping, and 2 affected mice died of umbilical cord bleeding. Ten affected mice survived to 4 months of age. Aside from the factor IX defect, carrier female and hemizygous male mice had no liver pathology by histologic examination, were fertile, and transmitted the mutation in the expected mendelian frequency. </p><p>Gu et al. (1999) found factor IX deficiency in 2 distinct dog breeds. In 1 breed, the disorder was associated with a large deletion mutation, spanning the entire 5-prime region of the F9 gene extending to exon 6. In the second breed, an insertion of approximately 5 kb disrupted exon 8. The insertion was associated with alternative splicing between a donor site 5-prime and acceptor site 3-prime to the normal exon 8 splice junction, with introduction of a new stop codon. </p><p>Brooks et al. (2003) found that mild hemophilia B in a large pedigree of German wirehaired pointers was caused by a line-1 insertion in the factor IX gene. The insertion could be traced through at least 5 generations and segregated with the hemophilia B phenotype. </p><p>Blood coagulation capacity increases with age in healthy individuals. Through extensive longitudinal analyses of human factor IX gene expression in transgenic mice, Kurachi et al. (1999) identified 2 essential age regulatory elements that they termed AE5-prime and AE3-prime. These elements are required and together are sufficient for normal age regulation of factor IX expression. AE5-prime, located between nucleotides -770 through -802, is a PEA3-related element present in the 5-prime upstream region of the gene encoding factor IX and is responsible for age-stable expression of the gene. AE3-prime, located in the middle of the 3-prime untranslated region, is responsible for age-associated elevation in mRNA levels. In a concerted manner, AE5-prime and AE3-prime recapitulate natural patterns of the advancing age-associated increase in factor IX gene expression. </p><p>In transgenic mice with hemophilia B Leyden (-20T-A; 300746.0001), which usually show amelioration of the disorder after puberty, Kurachi et al. (2009) found that expression of different F9 minigenes with or without the age-related stability element (ASE) in the 5-prime untranslated region resulted in different disease course. Mice with no ASE failed to show the Leyden phenotype, showing only transient F9 expression at puberty, whereas mice with ASE showed normal pubertal F9 recovery. These changes were not sex-dependent, indicating that testosterone and androgen are not responsible. Further studies showed that the transcription factor Ets1 (164720) was the specific ASE-binding protein responsible for its activation and F9 gene expression. In addition, F9 expression was abolished by hypophysectomy, but restored with growth hormone (GH; 139250) administration in both males and females. These results provided a molecular mechanism for the puberty-related Leyden phenotype. Kurachi et al. (2009) also generated transgenic mice expressing the Brandenberg F9 mutation (-26G-C; 300746.0097), which showed a severe phenotype without amelioration after puberty. </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>113 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 B LEYDEN</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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F9, -20T-A, PROMOTER
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<br />
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SNP: rs1178811105,
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gnomAD: rs1178811105,
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ClinVar: RCV000011304
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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>Veltkamp et al. (1970) described a variant of hemophilia B, termed hemophilia B Leyden (see 306900), in a Dutch family. The disorder was characterized by the disappearance of the bleeding diathesis as the patient aged. In affected individuals, plasma factor IX levels were less than 1% of normal before puberty, but after puberty factor IX activity and antigen levels rose steadily in a 1:1 ratio to a maximum of 50 to 60%. Briet et al. (1982) described a similar variant of hemophilia B that took a severe form early in life but remitted after puberty, with an increase in factor IX levels from below 1% of normal to about 50% of normal by age 80 years. Three pedigrees with 27 affected males with this disorder could be traced to a small village in the east of the Netherlands. In affected members of 2 Dutch pedigrees with hemophilia B Leyden, Reitsma et al. (1988) found that patients with hemophilia B Leyden had a T-to-A transversion in the promoter region of the F9 gene at position -20. The findings suggested that a point mutation in this region could lead to a switch from constitutive to steroid hormone-dependent gene expression. </p><p>Reijnen et al. (1992) demonstrated that the -20 promoter mutation disrupts the binding of hepatocyte nuclear factor-4 (HNF4; 600281), a member of the steroid hormone receptor superfamily of transcription factors. Studies also demonstrated that the G-to-C mutation at -26 (300746.0097) also disrupts the binding of HNF4. Whereas HNF4 transactivated the wildtype promoter sequence in liver and nonliver (e.g., HeLa) cell types, it transactivated the -20 mutated promoter to only a limited extent and the -26 mutated promoter not at all. The data suggested that HNF4 is a major factor controlling factor IX expression in the normal individual. Furthermore, the severity of the hemophilia phenotype appeared to be related directly to the degree of disruption of HNF4 binding and transactivation; the -26 G-to-C mutation was accompanied by a bleeding tendency did not ameliorate after puberty. </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 B LEYDEN</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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F9, -6G-A
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<br />
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SNP: rs1166164399,
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ClinVar: RCV000795083, RCV001815011, RCV004586929
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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>Fahner et al. (1988) found a G-to-A change at nucleotide -6 as the cause of hemophilia B Leyden (see 306900), in which a severe bleeding disorder in childhood becomes mild after puberty.</p><p>Crossley et al. (1990) also identified a G-to-A change at position -6 as the cause of hemophilia B Leyden. </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 B LEYDEN</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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F9, -6G-C
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<br />
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ClinVar: RCV000795083, RCV001815011, RCV004586929
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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>Attree et al. (1989) found a G-to-C change at nucleotide -6. Vidaud et al. (1993) cited evidence indicating that the G-C transversion at position -6 produces much milder hemophilia B Leyden (see 306900) than does the G-A transition at the same position (300746.0002). </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 B LEYDEN</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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F9, 1-BP DEL, +13A
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<br />
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SNP: rs2148352878,
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ClinVar: RCV000011307
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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>Reitsma et al. (1989) studied the F9 gene in a Greek patient and an American patient of Armenian descent with hemophilia B Leyden (see 306900). In one they found deletion of A at position +13 of the factor IX gene and in the other an A-to-G mutation at the same position (300746.0090), 32 bp downstream of the point mutation in the Dutch kindred (Reitsma et al., 1988). See also Crossley et al. (1989). Crossley and Brownlee (1990) identified a binding site for the CCAAT/enhancer binding protein (C/EBP) extending from +1 to +18. They showed that the A-to-G mutation at +13 prevents the binding of C/EBP to this site. Furthermore, they showed that C/EBP is capable of transactivating a cotransfected normal factor IX promoter but not the mutant promoter. </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>.0005 F9 POLYMORPHISM</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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F9, ILE-40PHE
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<br />
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SNP: rs150190385,
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gnomAD: rs150190385,
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ClinVar: RCV000291239, RCV001080823, RCV002488831, RCV003389717, RCV003970084, RCV004992192
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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>Koeberl et al. (1989) described a normal variant, isoleucine or phenylalanine, at position -40 in exon 1 of the F9 gene. </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>.0006 F9 POLYMORPHISM</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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F9, IVS1, 192A-G
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<br />
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ClinVar: RCV004991969
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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>Tanimoto et al. (1988) found a normal polymorphism, A to G, at nucleotide 192 in IVS1 of the F9 gene. </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>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 HEMOPHILIA B</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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|
F9, ARG-4TRP
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<br />
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SNP: rs1603264205,
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|
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ClinVar: RCV001001419, RCV001815019, RCV001860507
|
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|
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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 review of known factor IX mutations from all hemophilia B (306900) patients registered at the Malmo hemophilia center in Sweden and from the entire UK hemophilia population, Green et al. (1992) noted that 4 of 7 arg-4trp (R-4W) mutations, resulting from a 6364C-T transition, occurred on different haplotypes, indicating that they were independent mutations. </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>
|
|
<span class="mim-font">
|
|
<strong>.0008 HEMOPHILIA B</strong>
|
|
</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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|
F9, ARG-4GLN
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|
<br />
|
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|
|
SNP: rs1275708479,
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|
|
|
|
ClinVar: RCV001000159, RCV001815018, RCV001869416, RCV002462253
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|
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|
|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant has been called factor IX San Dimas and factor IX Kawachinagano.</p><p>In a case (designated Ox3) of severe hemophilia B (306900) of the CRM-positive type, Bentley et al. (1986) of Oxford University found mutation of arginine to glutamine at position -4, leading to defective cleavage of the N-terminal propeptide. The type of mutation in this mutant factor IX is similar to that in the procollagen molecule (either the alpha-1 or alpha-2 chain of type I collagen) in cases of type VII Ehlers-Danlos syndrome. Two proteolytic cleavages normally occur to remove the prepeptide and the propeptide regions. The mutant F9 had 18 additional amino acids on the N-terminal portion. Normally the signal peptidase cleaves the peptide bond between residues -18 and -19. Further cleavage to mature F9 depends on the arginine residue at -4. Arginine at -4 shows evolutionary conservation in factor X, prothrombin, C3, C4, C5, and tissue type plasminogen activator--all proteins that, like F9, are processed by site-specific trypsin-like enzymes. In addition to the CRM-positive and CRM-negative forms, there is a CRM-reduced class. Sugimoto et al. (1989) demonstrated by amino acid sequence that the mutant factor IX retained the propeptide region of 18 amino acids due to a substitution of arginine at position -4 by glutamine. They assumed that this attached propeptide region of the molecule directly interferes with the adjacent NH(2)-terminus and prevents the metal-induced conformational changes that are essential for biologic activity of normal factor IX. </p><p>Ware et al. (1989) studied the intragenic defect in factor IX San Dimas, which was derived from a patient with moderately severe hemophilia B (306900) who had 98% factor IX antigen but very low factor IX clotting activity. They found that a G-to-A transition in exon 2 of the F9 gene resulted in the substitution of a glutamine for an arginine codon -4 in the propeptide of factor IX. The variant protein circulated in the plasma as profactor IX with a mutant 18-amino acid propeptide still attached. Factor IX San Dimas shows similarities to factor IX Cambridge, which has a substitution of serine for arginine at -1 (300746.0009). </p><p>Factor IX Kawachinagano is a mutant factor IX protein initially recognized in a patient with severe hemophilia B who had 46% of normal factor IX antigen but no detectable clotting activity. This mutant factor IX is not activated by factor XIa in the presence of calcium ions. Sugimoto et al. (1989) determined that factor IX Kawachinagano results from an arg-to-gln substitution at the -4 position of the F9 gene. The substitution resulted in impaired function of the Gla-domain caused by an attached propeptide region. </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>
|
|
<span class="mim-font">
|
|
<strong>.0009 HEMOPHILIA B</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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|
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F9, ARG-1SER
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<br />
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ClinVar: RCV000011311
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|
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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>Diuguid et al. (1986) found that mutant factor IX Cambridge, isolated from a patient with severe hemophilia B (306900), has an 18-residue propeptide attached to its NH2-end. A point mutation at residue -1, from arginine to serine, precluded cleavage of the propeptide by the processing protease and interfered also with gamma-carboxylation of the mutant factor IX. The last effect indicates the importance of the leader sequence in substrate recognition by the vitamin K-dependent carboxylase. </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>
|
|
<span class="mim-font">
|
|
<strong>.0010 HEMOPHILIA B</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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|
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F9, GLU7ASP
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<br />
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|
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ClinVar: RCV000011312
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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>See Winship (1989).</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>
|
|
<span class="mim-font">
|
|
<strong>.0011 HEMOPHILIA B</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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F9, GLN11TER
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<br />
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|
|
SNP: rs137852223,
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ClinVar: RCV000011313
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|
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>See Winship (1989); the patient studied had a severe form of hemophilia B (306900).</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>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 HEMOPHILIA B</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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F9, CYS18ARG
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<br />
|
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|
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SNP: rs387906474,
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ClinVar: RCV000011314
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|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Information was provided by Bertina (1989); the patient studied had a severe form of hemophilia B (306900).</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, GLU27LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906475,
|
|
|
|
|
|
|
|
ClinVar: RCV000011316, RCV004689413
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant has been designated factor IX Seattle-3.</p><p>Chen et al. (1989) studied 5 patients with severe hemophilia B (306900) and detectable factor IX antigen that showed altered reactivity to a specific polyclonal antibody fraction or monoclonal anti-factor IX antibody. By the PCR technique, they identified a single base transition in each of the 5 families. Three different mutations were identified: factor IX Seattle-3 showed a G-to-A transition in exon 2, changing the codon for glu27 to lys; factor IX Durham showed a G-to-A transition in exon 4, changing the codon for gly60 to ser; and factor IX Seattle-4 showed a G-to-A transition in exon 8, changing arg248 to gln in exon 8. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, GLU27VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852226,
|
|
|
|
|
|
|
|
ClinVar: RCV000011317
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant has been designated factor IX Chongqing.</p><p>Wang et al. (1990) studied a Chinese patient with sporadic hemophilia B (306900) of severe form. A defect in the factor IX Gla domain was suspected because of low antigen on an assay using a calcium-dependent antibody fraction. Since the Gla domain is coded mainly by exon 2, Wang et al. (1990) amplified and sequenced the exon and found an A-to-T substitution at nucleotide 6455. The transversion changed glutamic acid-27 to valine. In leukocyte DNA from the patient's mother, the nucleotide sequence of exon 2 was entirely normal. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ARG29TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852227,
|
|
|
|
|
|
|
|
ClinVar: RCV000011318, RCV000696946, RCV001810844
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Green et al. (1989). This mutation, which is due to a transition at a CpG dinucleotide, was found by Koeberl et al. (1990) in 2 cases of severe hemophilia B (306900). Koeberl et al. (1990) estimated that approximately 1 in 4 individuals with hemophilia B can be expected to have a mutation at arginine and concluded that nonsense mutations at 1 of the 6 arginine residues are common causes of severe hemophilia. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ARG29GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852228,
|
|
|
|
|
|
gnomAD: rs137852228,
|
|
|
|
|
|
ClinVar: RCV000011319, RCV000757260, RCV000852079, RCV001851790, RCV002490353
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Koeberl et al. (1989) and Zhang et al. (1989). The hemophilia (306900) was clinically mild. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, GLU33ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852229,
|
|
|
|
|
|
|
|
ClinVar: RCV000011320
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Koeberl et al. (1989). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, IVS3DS, T-G
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011409
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Brownlee (1988) described a GT-to-GG donor splice site mutation in IVS3 in association with severe hemophilia B (306900).</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ASP47GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852230,
|
|
|
|
|
|
|
|
ClinVar: RCV000011322
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Davis et al. (1984, 1987) found that factor IX Alabama, a CRM+ mutation responsible for a clinically moderate form of hemophilia B (306900), has an adenine to guanine transition in the first nucleotide of exon d, causing substitution of glycine for aspartic acid (GAT to GGT) at residue 47. The structural defect in factor IX Alabama results in a molecule with 10% of normal coagulant activity. McCord et al. (1990) concluded that the asp47-to-gly mutation, which occurs in a calcium-binding site, results in a loss of a stable calcium-mediated conformational change, leading to improper interaction with factor VIIIa and factor X. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, GLN50PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852231,
|
|
|
|
|
|
|
|
ClinVar: RCV000011323, RCV004783723
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Lozier et al. (1989). The hemophilia (306900) was clinically severe.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, PRO55ALA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852232,
|
|
|
|
|
|
gnomAD: rs137852232,
|
|
|
|
|
|
ClinVar: RCV000011324, RCV001810845, RCV003764550
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant has been designated factor IX Hollywood.</p><p>See Green et al. (1989) and Spitzer et al. (1989). The hemophilia (306900) was clinically mild. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, GLY60SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852233,
|
|
|
|
|
|
gnomAD: rs137852233,
|
|
|
|
|
|
ClinVar: RCV000011325, RCV000795416, RCV001810846, RCV002247325, RCV002496325, RCV003430636
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant has been designated factor IX Durham.</p><p>In 2 men with mild hemophilia B (306900), Denton et al. (1988) found that the highly conserved gly60 residue had been changed to ser. The mutation was accompanied by defective epitope expression in the 2 patients, suggesting that a change in the tertiary structure of the EGF-like domain is the cause of the mild hemophilia B. See Chen et al. (1989). </p><p>Poort et al. (1989) found the same mutation in a Dutch family. A G-to-A change at position 10430 in exon 4 was responsible. The presence of the same mutation in 3 patients from distinct geographic areas confirmed the notion that CpG dinucleotides are 'hotspots' for mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0023 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ASP64GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852234,
|
|
|
|
|
|
|
|
ClinVar: RCV000011326
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Green et al. (1989). The hemophilia (306900) was clinically mild. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0024 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, GLY114ALA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852235,
|
|
|
|
|
|
|
|
ClinVar: RCV000011327
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Winship et al. (1989). The hemophilia (306900) was clinically severe. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0025 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ASN120TYR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852236,
|
|
|
|
|
|
|
|
ClinVar: RCV000011328
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Green et al. (1989). The hemophilia (306900) was clinically severe. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0026 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ARG145CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894807, rs137852237,
|
|
|
|
|
|
gnomAD: rs137852237,
|
|
|
|
|
|
ClinVar: RCV000011330, RCV001390295, RCV004700216, RCV005042030
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Liddell et al. (1989) described a molecular defect in factor IX Cardiff, a variant that showed faulty activation with the production of a stable reaction product with a molecular weight compatible with that of a putative light chain-activation intermediate. A single C-to-T transition was discovered that changed the arg residue at position 145 (the first residue of the first bond in the activation peptide) to a cys. The hemophilia (306900) was clinically moderate to severe. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0027 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ARG145HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852238,
|
|
|
|
|
|
gnomAD: rs137852238,
|
|
|
|
|
|
ClinVar: RCV000011331, RCV000851602, RCV001390296, RCV002247326, RCV002284168
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Factor IX Chapel Hill, a CRM+ variant of mild hemophilia B (306900), results from an arg-to-his change at residue 145, which prevents cleavage at one of the activation sites (Noyes et al., 1983). See Koeberl et al. (1989). Suehiro et al. (1990) concluded that the arg145-to-his substitution impairs the cleavage between the light chain and the activation peptide by factor XIa/calcium ions. </p><p>This variant has also been called factor IX Nagoya-3.</p>
|
|
</span>
|
|
</div>
|
|
|
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|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0028 DEEP VENOUS THROMBOSIS, PROTECTION AGAINST</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, THR148ALA
|
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|
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|
|
<br />
|
|
|
|
SNP: rs6048,
|
|
|
|
|
|
gnomAD: rs6048,
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|
|
|
|
|
ClinVar: RCV000011334, RCV000244191, RCV000396693, RCV001521358, RCV001701639, RCV001810847
|
|
|
|
|
|
</span>
|
|
</div>
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|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>McGraw et al. (1985) identified a common polymorphism at the third amino acid residue in the activation peptide of the F9 gene: an A-to-G transition resulting in a thr148-to-ala (T148A) substitution. </p><p>Winship and Brownlee (1986) also identified the 20422A-G transition in the F9 gene and found that it gave rise to an MnlI RFLP. However, technical problems made it difficult to detect the polymorphic fragments by conventional Southern blotting. The polymorphism as identified by oligonucleotide probes was used for linkage studies in a 3-generation family. </p><p>Graham et al. (1988) showed that the F9 protein with thr148 reacted to the mouse monoclonal antibody, whereas that with ala148 did not. The polymorphism is referred to as the F9 Malmo polymorphism; positive reactors are designated Malmo A, and negative reactors are designated Malmo B. Strong linkage disequilibrium was found with 2 other intragenic RFLPs. </p><p>Bezemer et al. (2008) reported that the G allele (ala148) of F9 Malmo (rs6048) was associated with a 15 to 43% decrease in deep vein thrombosis risk compared to the A allele in 3 case-control studies of deep vein thrombosis. This common variant has a minor allele frequency of 0.32. The substitution occurs in the portion of the factor IX zymogen that is cleaved from the zymogen to activate factor IX. The authors noted that this variant had not been reported to be associated with hemophilia B (306900). In a follow-up study from 3 case-control studies involving a total of 1,445 male patients with deep venous thrombosis and 2,351 male controls, Bezemer et al. (2009) found that the G allele of F9 Malmo conferred protection against deep venous thrombosis (odds ratio of 0.80); see 300807. The pooled corresponding odds ratio in a comparable number of women with deep venous thrombosis was 0.89. However, factor IX antigen level, factor IX activation peptide levels, and endogenous thrombin potential did not differ between the F9 Malmo genotypes. Although F9 Malmo was the most strongly associated with protection from deep vein thrombosis, the biologic mechanism remained unknown. </p>
|
|
</span>
|
|
</div>
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<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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|
|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0029 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, GLN173TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852239,
|
|
|
|
|
|
|
|
ClinVar: RCV000011335
|
|
|
|
|
|
</span>
|
|
</div>
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|
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|
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Koeberl et al. (1989). The hemophilia (306900) was clinically severe. </p>
|
|
</span>
|
|
</div>
|
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|
|
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|
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|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0030 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ARG180TRP
|
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|
|
<br />
|
|
|
|
SNP: rs137852240,
|
|
|
|
|
|
|
|
ClinVar: RCV000011336, RCV001810848, RCV002512970, RCV003407315
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant has been called factor IX B(M) Nagoya and factor IX Deventer.</p><p>Suehiro et al. (1989) demonstrated substitution of tryptophan for arginine at position 180 in the factor IX protein of a patient with severe hemophilia B (306900). Bertina et al. (1990) found the same mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0031 HEMOPHILIA B(M)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ARG180GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852241,
|
|
|
|
|
|
|
|
ClinVar: RCV000011337, RCV001727513, RCV004752695, RCV004814880
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant has been called factor IX Hilo and factor IX Novara.</p><p>A subset of hemophilia B patients have a prolonged prothrombin time (PT) when exposed to bovine (or ox) brain tissue; these CRM+ patients are classified as having hemophilia B(M) (see 306900). Huang et al. (1989) demonstrated a point mutation in a hemophilia B(M) variant, factor IX Hilo. Glutamine (CAG) was substituted for arginine (CGG) at amino acid 180 in exon 6 (G-to-A at nucleotide 20519). Bertina et al. (1990) found the same mutation. The hemophilia was clinically severe. </p><p>Lefkowitz et al. (1993) noted that the bovine brain tissue in studies of hemophilia B(M) is the source of thromboplastin, or tissue factor (F3; 134390); PT times determined with thromboplastin from rabbit brain or human brain are not reported to be prolonged. However, in various studies of factor IX Hilo, Lefkowitz et al. (1993) found that either normal F9 or Hilo F9 prolonged the PT regardless of the tissue factor source, but the prolongation required high concentrations of factor IX when rabbit or human brain was used. With bovine thromboplastin, factor IX Hilo was significantly better than normal factor IX at prolonging the PT. In addition, the prolongation times depended on the amounts of factors IX and X used in the assays. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0032 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, VAL181PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906477,
|
|
|
|
|
|
|
|
ClinVar: RCV000011338
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant has been designated factor IX Milano. See Bertina et al. (1989, 1990). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0033 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, VAL182PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852243,
|
|
|
|
|
|
gnomAD: rs137852243,
|
|
|
|
|
|
ClinVar: RCV000011339
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Sakai et al. (1989) found that the defect in hemophilia B (306900) (factor IX Kashihara), a severe hemorrhagic disorder in which a factor IX antigen is present in normal amounts but factor IX biological activity is markedly reduced, has a defect in valine-182 (equivalent to valine-17 in the chymotrypsin numbering system), which is replaced by phenylalanine. The change appears to hinder sterically the cleavage of arg180-val181 required for the activation of this zymogen. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0034 HEMOPHILIA B(M)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, VAL182LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852243,
|
|
|
|
|
|
gnomAD: rs137852243,
|
|
|
|
|
|
ClinVar: RCV000011340
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant has been designated factor IX Cardiff II. See Taylor et al. (1989). One of the variant forms of hemophilia B in which normal levels of a dysfunctional factor IX protein is found is referred to as hemophilia B(M) (see 306900) (Hougie and Twomey, 1967; Kasper et al., 1977). The abnormal factor IX results in prolongation of the prothrombin time performed with ox brain thromboplastin. In 1 such patient, Taylor et al. (1990) found a G-to-C transversion at nucleotide 20524, changing the amino acid encoded at residue 182 from valine to leucine. The abnormal factor IX protein showed a normal molecular weight and normal calcium-binding properties. Activation of the mutant factor IX with factor XIa showed normal proteolytic cleavage. Hemophilia was clinically mild in these patients. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0035 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, GLN191TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852244,
|
|
|
|
|
|
|
|
ClinVar: RCV000011341
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Matsushita et al. (1989). The hemophilia (306900) was clinically severe.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0036 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, GLN191LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852245,
|
|
|
|
|
|
|
|
ClinVar: RCV000011342
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Information was provided by Chen and Thompson (1989). The hemophilia (306900) was clinically severe.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0037 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, TRP194TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1603265827,
|
|
|
|
|
|
|
|
ClinVar: RCV001001415, RCV002282420
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Green et al. (1989). The hemophilia (306900) was clinically severe. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0038 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, IVS6DS, G-T
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1603265832,
|
|
|
|
|
|
|
|
ClinVar: RCV000011343
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a severely affected, antigen-negative (CRM-negative) patient with hemophilia B (306900), Rees et al. (1985) found a point mutation in the F9 gene that changed an obligatory GT to a TT within the donor splice junction of exon 6. This was comparable to point mutations in splice junctions that lead to beta-zero-thalassemia (see 613985). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0039 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, TRP215TER
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011344
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Information was provided by Chen and Thompson (1989). The hemophilia (306900) was clinically severe.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0040 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, CYS222TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852246,
|
|
|
|
|
|
|
|
ClinVar: RCV000011345
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Koeberl et al. (1989). The hemophilia (306900) was clinically moderate in severity. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0041 F9 POLYMORPHISM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, VAL227VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1800455,
|
|
|
|
|
|
gnomAD: rs1800455,
|
|
|
|
|
|
ClinVar: RCV000011346, RCV000402083, RCV001086730, RCV003934824, RCV004703182
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>A T-to-C substitution in codon 227 produced no change in amino acid (Koeberl et al., 1989). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0042 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ALA233THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906478,
|
|
|
|
|
|
|
|
ClinVar: RCV000011347
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Koeberl et al. (1989). The hemophilia (306900) was clinically mild. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0043 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, IVS7AS, G-A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1439169192,
|
|
|
|
|
|
|
|
ClinVar: RCV001812588, RCV001815042, RCV003772215
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Matsushita et al. (1989) found a G-to-A substitution in the last nucleotide in the 3-prime acceptor splice site of IVS7. The hemophilia (306900) was severe and was associated with a serum inhibitor.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0044 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ARG248TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852248,
|
|
|
|
|
|
gnomAD: rs137852248,
|
|
|
|
|
|
ClinVar: RCV000011333, RCV001000167, RCV001069256, RCV004791215
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Green et al. (1989). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0045 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ARG248GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852249,
|
|
|
|
|
|
|
|
ClinVar: RCV000011348, RCV000814168, RCV000851909, RCV004724733
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant has been called factor IX Seattle-4 and factor IX Dreihacken.</p><p>See Chen et al. (1989). In a patient with hemophilia B (306900), Ludwig et al. (1992) identified a G-to-A transition at nucleotide 30864 of the F9 gene, resulting in replacement of arg248 by gln in the mature factor IX protein. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0046 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ARG252TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852250,
|
|
|
|
|
|
|
|
ClinVar: RCV000011349, RCV001001417, RCV002512971, RCV004819206
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In male sibs with severe hemophilia B (306900), Chen et al. (1989) demonstrated a C-to-T change at nucleotide 30875 resulting in a nonsense mutation (TGA) and termination of protein synthesis at amino acid residue 252. The change involved a CpG dinucleotide. The protein was designated factor IX Portland. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0047 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ASN260SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852251,
|
|
|
|
|
|
|
|
ClinVar: RCV000011350
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Koeberl et al. (1989). The hemophilia (306900) was clinically mild. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0048 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, PRO287LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852252,
|
|
|
|
|
|
|
|
ClinVar: RCV000011351
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Information was provided by Chen and Thompson (1989). The hemophilia (306900) was clinically severe.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0049 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ALA291PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852253,
|
|
|
|
|
|
|
|
ClinVar: RCV000011352
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Winship et al. (1989). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0050 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, THR296MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852254,
|
|
|
|
|
|
|
|
ClinVar: RCV000011353, RCV000792734, RCV000851963, RCV001810849, RCV004752696, RCV005042031
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Koeberl et al. (1989). Hemophilia B (306900) is an X-linked disorder relatively frequent among the Amish, particularly those living in Ohio (Wall et al., 1967). Ketterling et al. (1991) demonstrated that the Amish mutation is thr296-to-met. Among 64 families of European descent with hemophilia B, Ketterling et al. (1991) found that 6 (9%) had a C-to-T transition at base 31008 leading to the thr296-to-met mutation in the catalytic domain of factor IX. Five of the patients had the same haplotype and were known or presumed to be from the Amish group. All 6 patients had clinically mild disease. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0051 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, VAL307ALA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852255,
|
|
|
|
|
|
|
|
ClinVar: RCV000011354, RCV003764551, RCV004730842
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Bottema et al. (1989). The hemophilia (306900) was clinically mild.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0052 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, GLY309VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852256,
|
|
|
|
|
|
|
|
ClinVar: RCV000011355
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Thompson et al. (1989). The hemophilia (306900) was clinically severe.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0053 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, TRP310TER
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011356
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Wang et al. (1990). The hemophilia (306900) was clinically severe. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0054 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, GLY311ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852257,
|
|
|
|
|
|
|
|
ClinVar: RCV000011357, RCV000851648
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Koeberl et al. (1989). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0055 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ARG333TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852258,
|
|
|
|
|
|
gnomAD: rs137852258,
|
|
|
|
|
|
ClinVar: RCV000011358, RCV001000157, RCV001851791, RCV004791216
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Zhang et al. (1989). This mutation, due to a transition at a CpG dinucleotide, was found by Koeberl et al. (1990) in 2 patients with severe hemophilia B (306900). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0056 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ARG333GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852259,
|
|
|
|
|
|
|
|
ClinVar: RCV000011359, RCV000851995, RCV001000156, RCV001851792, RCV004799740
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Tsang et al. (1988) characterized the mutation in factor IX London-2, which caused a severe CRM+ hemophilia B (306900). Tsang et al. (1988) found a G-to-A transition at position 31119. The mutation resulted in substitution of glutamine for arginine at position 333. This arginine residue is conserved in the catalytic domain of normal human and bovine factor IX, factor X, and prothrombin. This mutation pinpoints a functionally critical feature of factor IX which may be involved in substrate or cofactor binding. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0057 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, CYS336ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852260,
|
|
|
|
|
|
|
|
ClinVar: RCV000011360, RCV003764552
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Green et al. (1989). The hemophilia (306900) was clinically of moderate severity. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0058 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ARG338TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852261,
|
|
|
|
|
|
gnomAD: rs137852261,
|
|
|
|
|
|
ClinVar: RCV000011361, RCV001000158, RCV001048961, RCV003398481
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Ludwig et al. (1989) demonstrated a C-to-T transition at amino acid 338, converting the CGA codon for arginine to a TGA stop codon. The variant was called factor IX Bonn-1. The hemophilia (306900) was clinically severe. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0059 REMOVED FROM DATABASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0060 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, MET348VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852262,
|
|
|
|
|
|
|
|
ClinVar: RCV000011362
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Information was provided by Chen and Thompson (1989). The hemophilia (306900) was clinically of moderate severity.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0061 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, SER360LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852263,
|
|
|
|
|
|
|
|
ClinVar: RCV000011363
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Information was provided by Chen and Thompson (1989). The hemophilia (306900) was clinically of moderate severity.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0062 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, GLY363VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906479,
|
|
|
|
|
|
|
|
ClinVar: RCV000011364
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Spitzer et al. (1988). The hemophilia (306900) was clinically of moderate severity. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0063 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, GLY367ARG
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011365
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Information was provided by Chen and Thompson (1989). The hemophilia (306900) was clinically severe.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0064 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, PRO368THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852265,
|
|
|
|
|
|
gnomAD: rs137852265,
|
|
|
|
|
|
ClinVar: RCV000011366
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Bertina et al. (1989, 1990). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0065 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, PHE378LEU
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011367
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Information was provided by Chen and Thompson (1989). The hemophilia (306900) was clinically severe.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0066 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ALA390GLU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852266,
|
|
|
|
|
|
|
|
ClinVar: RCV000011368
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Information was provided by Thompson (1989). The hemophilia (306900) was clinically of moderate severity.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0067 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ALA390VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852266,
|
|
|
|
|
|
|
|
ClinVar: RCV000011369
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Spitzer et al. (1988) found substitution of valine for alanine at position 390, resulting from a single base substitution (C-to-T) in exon 8. Sugimoto et al. (1988) demonstrated substitution of valine for alanine at position 390 in the catalytic domain as the molecular defect in factor IX Niigata. The patient had a moderately severe form of hemophilia B (306900) with a normal level of factor IX antigen but very low clotting activity. </p><p>Bertina et al. (1990) referred to this mutation as factor IX Lake Elsinore. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0068 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, GLY396ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852267,
|
|
|
|
|
|
|
|
ClinVar: RCV000011370
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Attree et al. (1989) designed a strategy allowing rapid analysis of the critical serine protease catalytic domain of activated factor IX, encoded by exons 7 and 8 of the gene. The method involved enzymatic amplification of genomic DNA, analysis of the amplification products by denaturing gradient gel electrophoresis, and direct sequencing of the fragments displaying an altered melting behavior. They used this procedure to characterize 2 'new' mutations in hemophilia B (306900): factor IX Angers, a G-to-A substitution generating an arg in place of a gly at amino acid 396 of the mature factor IX protein; and factor IX Bordeaux, an A-to-T substitution introducing a nonsense codon in place of the normal codon for lys at position 411 (300746.0071). The hemophilia was clinically severe.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0069 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ILE397THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852268,
|
|
|
|
|
|
|
|
ClinVar: RCV000011371, RCV001382695, RCV001810850, RCV005042032
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Ware et al. (1988) demonstrated that the defect in factor IX(Long Beach) is a result of a thymine-to-cytosine transition leading to the substitution of a threonine codon (ACA) for an isoleucine codon (ATA) in exon 8 of the F9 gene. In a case of hemophilia B (306900) of moderate severity, Geddes et al. (1989) found a mutation in the protease domain of factor IX that changed the codon for isoleucine-397 (ATA) to a threonine codon (ACA). The resulting abnormal protein had been named factor IX(Vancouver) (Geddes et al., 1987). Thus, factor IX Long Beach, factor IX Vancouver, and factor IX Los Angeles have the same defect. In 11 of 65 consecutive males with hemophilia B (17%), Bottema et al. (1990) found this mutation, a T-to-C transition at base 31311, which substitutes threonine for isoleucine-397. The 11 patients were of western European descent and had the same haplotype. Judging from the frequency of this haplotype, the probability of the same mutation occurring independently 11 times in this haplotype was considered to be minuscule. Despite the lack of overlapping pedigrees, a common ancestor for these patients was suspected. The clinical symptoms were considerably moderate/mild. Sarkar et al. (1991) found this mutation in 2 females with hemophilia B. Both were heterozygous, coming from unrelated families. Nonrandom X inactivation was proposed, although other possibilities included a second undetected intronic or promoter mutation. Chen et al. (1991) found this mutation in 7 families which all shared a rare haplotype, suggesting a common ancestor. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0070 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, TRP407ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852269,
|
|
|
|
|
|
|
|
ClinVar: RCV000011372
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Koeberl et al. (1989). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0071 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, LYS411TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852270,
|
|
|
|
|
|
|
|
ClinVar: RCV000011373
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant has been designated factor IX Bordeaux. See Attree et al. (1989). The hemophilia (306900) was clinically severe. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0072 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, EX1-8DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011374
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Deletions of various sizes deleting exons 1-8 were reported by Giannelli et al. (1983), Anson et al. (1988), Taylor et al. (1988), Matthews et al. (1987), Ludwig et al. (1989), Wadelius et al. (1988), Bernardi et al. (1985), Mikami et al. (1987), Tanimoto et al. (1988), Koeberl et al. (1989), and Hassan et al. (1985). Some of the deletions were associated with development of inhibitors and others of comparable size were not. The hemophilia (306900) was clinically severe. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0073 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, EX1DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011375
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Ludwig et al. (1989) described deletion of exon 1 in a case of severe hemophilia B (306900). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0074 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, EX1-3DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011376
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Ludwig et al. (1989). The hemophilia (306900) was severe and was associated with serum inhibitors. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0075 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, EX2-8DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011377
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Information was provided by Chen and Thompson (1989). The hemophilia (306900) was severe and was associated with serum inhibitors.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0076 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, EX4-5DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011378
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Ludwig et al. (1989). The hemophilia (306900) was clinically severe. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0077 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, EX4DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011379
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Vidaud et al. (1986). The hemophilia (306900) was clinically severe. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0078 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, EX4INS
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011380
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with moderate to severe hemophilia B (306900), Chen et al. (1988) found a large insertion in the F9 gene, which appeared to have originated from outside the gene rather than to represent an internal duplication. The variant was called factor IX El Salvador for the birthplace of the patient. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0079 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, EX5-8DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011381
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Matthews et al. (1987) and Peake et al. (1989). The hemophilia (306900) was severe and was associated with serum inhibitors. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-text-font">
|
|
<strong>.0080 MOVED TO 300746.0098</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0081 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, EX7DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011383
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See Ludwig et al. (1989). The hemophilia (306900) was clinically severe. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0082 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, 1-BP DEL, ASP85FS
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011384
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant has been designated factor IX Seattle-2.</p><p>In a case of severe hemophilia B (306900), Schach et al. (1987) found deletion of a single adenine nucleotide in exon 5. This resulted in a frameshift that converted an aspartic acid at position 85 in the protein to a valine and the formation of a stop signal at position 86. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0083 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, VAL328PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852271,
|
|
|
|
|
|
|
|
ClinVar: RCV000011385, RCV001001418
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Winship (1990) found a substitution of valine by phenylalanine at residue 328 in exon h of factor IX in a patient with hemophilia B (306900) referred to as hemophilia B Oxford h5 (Oxh5). The substitution was caused by a G-to-T transversion at nucleotide 31103. Arg327-val328 is the major thrombin cleavage site in factor IX. Winship (1990) suggested that the mutant protein may have increased susceptibility to thrombin cleavage with resulting in vivo instability of the mutant protein. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0084 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ARG116TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852272,
|
|
|
|
|
|
|
|
ClinVar: RCV000011386, RCV001000188, RCV003764553
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 4-year-old boy with severe hemophilia B (306900), an isolated case in his family, Montandon et al. (1990) identified a C-to-T transition at residue 17762 resulting in a translation stop at codon arginine-116. A second mutation in this patient at residue 30890 resulted in a his257-to-tyr substitution (300746.0085); this mutation was subsequently shown to be neutral by the fact that its origin preceded the maternal grandfather and it produced no reduction in factor IX coagulant and antigen level in the grandfather. On the other hand, analysis of other family members showed that the mutation for arg116-to-ter had occurred at gametogenesis in the paternal grandfather. The patient was referred to as Malmo 7. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0085 F9 POLYMORPHISM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, HIS257TYR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1801202,
|
|
|
|
|
|
gnomAD: rs1801202,
|
|
|
|
|
|
ClinVar: RCV000011387, RCV001081157, RCV001167683, RCV002496326, RCV003944813
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 300746.0084.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0086 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, CYS350SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852273,
|
|
|
|
|
|
|
|
ClinVar: RCV000011388
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Taylor et al. (1991) described a male patient with hemophilia B (306900) in whom they documented somatic mosaicism for a cysteine-to-serine alteration at codon 350 in the catalytic domain of factor IX. The mutation resulted from a G-to-C transversion at nucleotide 31170. Using a combination of allele-specific oligonucleotide hybridization and differential termination of primer extension, Taylor et al. (1991) showed that hepatic, renal, smooth muscle, and hematopoietic cells possessed both normal and mutant factor IX sequences. An additional unusual phenomenon in this pedigree was the presence of 2 females in successive generations with moderately severe factor IX deficiency. These females were the daughter and granddaughter of the proband. No evidence of X chromosome or autosome cytogenetic abnormalities was found, no additional sequence alterations were identified in the factor IX gene in either woman and no gross changes were observed on Southern analysis of the regulatory regions in the 5-prime and 3-prime ends of the gene. The normal X chromosomes of the 2 women were shown to have different haplotypes at the factor IX locus. Taylor et al. (1991) speculated that the X chromosome bearing the normal factor IX gene has been exclusively inactivated in both affected women, possibly secondary to a second genetic change affecting the primary inactivation center on the mutant X chromosome and resulting in a failure of inactivation of the mutant factor IX sequences. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0087 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ASP64ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852274,
|
|
|
|
|
|
|
|
ClinVar: RCV000011389
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Winship and Dragon (1991) described a G-to-A transition at nucleotide 10442 of the F9 gene, resulting in substitution of asparagine for aspartic acid-64 (D64N). The change resulted in a functionally defective factor IX molecule that altered calcium-binding properties. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0088 HEMOPHILIA B LEYDEN</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, +8T-C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2148352869,
|
|
|
|
|
|
|
|
ClinVar: RCV000011390
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Anglo-Irish family living in New Zealand, Royle et al. (1991) identified a T-to-C transition at position +8 in the promoter region of the F9 gene as the cause of hemophilia B Leyden (see 306900). This mutation is situated within the repeat consensus sequence in the transcribed but untranslated portion of the gene. The mutation had arisen de novo in the proband. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0089 HEMOPHILIA B LEYDEN</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, -5A-T, PROMOTER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1927322453,
|
|
|
|
|
|
|
|
ClinVar: RCV000011391
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 3-year-old boy with hemophilia B Leyden (306900), Picketts et al. (1992) described an A-to-T transversion at position -5 of the factor IX promoter. Picketts et al. (1993) identified 5 transcription factor binding sites within the F9 promoter and showed that the Leyden mutation at nucleotide -5 interfered with the binding of proteins to 1 of 3 newly identified sites. The correlation between the postpubertal recovery of these mutants and the induction of the transcription factor DBP (D-site binding protein; 124097) led Picketts et al. (1993) to the discovery of a synergistic interaction between DBP and C/EBP (CCAAT/enhancer binding protein; 116897). </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>.0090 HEMOPHILIA B LEYDEN</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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F9, +13A-G
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<br />
|
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|
|
SNP: rs1927322926,
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|
|
|
ClinVar: RCV000011392, RCV003764554, RCV004791217
|
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|
</span>
|
|
</div>
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<div>
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<span class="mim-text-font">
|
|
<p>As indicated in 300746.0004, Reitsma et al. (1989) found an A-to-G mutation at position +13 of the factor IX gene in an American patient of Armenian descent with hemophilia B Leyden (see 306900). </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>.0091 HEMOPHILIA B</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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F9, GLY311GLU
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<br />
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SNP: rs137852275,
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ClinVar: RCV000011393, RCV001810851
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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 B (306900), Miyata et al. (1991) identified a G-to-A substitution in exon 8 resulting in replacement of glycine-311, a highly conserved amino acid residue among serine proteases, by glutamic acid. The mutation resulted in complete loss of both coagulant activity and esterase activity. The variant was designated factor IX Amagasaki. </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>.0092 HEMOPHILIA B</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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F9, IVS4, 4442-BP DEL
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<br />
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ClinVar: RCV000011394
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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 17-year-old male with severe hemophilia B (306900), Solera et al. (1992) found a 4,442-bp deletion, which removed both the donor splice site located at the 5-prime end of intron d and the last 2 coding nucleotides located at the 3-prime end of exon 4. This fragment had been replaced by a 47-bp sequence from the normal factor IX gene, inserted in inverted orientation. They identified 2 homologous sequences at the ends of the deleted DNA fragment. The variant was designated factor IX Madrid-2. </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>.0093 HEMOPHILIA B</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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F9, SER365ILE
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<br />
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SNP: rs137852276,
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ClinVar: RCV000011395
|
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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>Ludwig et al. (1992) described the molecular basis of hemophilia B (306900) in 5 patients who had neither deletions nor rearrangements of the F9 gene. By enzymatic amplification and sequencing of all exons and promoter regions, a causative mutation in the protease domain was identified in each patient. The first was a G-to-T transversion at nucleotide 31215, leading to substitution of isoleucine for serine-365. The variant was designated factor IX Schmallenberg. </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>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0094 HEMOPHILIA B</strong>
|
|
</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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F9, SER365GLY
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<br />
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SNP: rs137852277,
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|
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ClinVar: RCV000011396, RCV002512972
|
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with hemophilia B (306900), Ludwig et al. (1992) demonstrated an A-to-G transition at nucleotide 31214 resulting in replacement of serine-365 by glycine. The variant was designated factor IX Varel. The mutation occurs at the same codon as that involved in factor IX Schmallenberg (300746.0093). This patient also had a silent mutation (GAT to GAC) at asp364. Thus, this patient had a double basepair substitution of TA to CG at nucleotides 31213 and 31214 but only a single amino acid change of ser365-to-gly. This patient also developed an antibody to factor IX during replacement therapy, which suggested that deletion of the factor IX gene is not necessary for development of antibody. </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>.0095 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ASP364HIS
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|
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<br />
|
|
|
|
SNP: rs137852278,
|
|
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|
|
|
|
ClinVar: RCV000011397
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with hemophilia B (306900), Ludwig et al. (1992) identified a G-to-C transversion at nucleotide 31211, resulting in substitution of his for asp364. The variant was designated factor IX Mechtal. </p>
|
|
</span>
|
|
</div>
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<div>
|
|
<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>.0096 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, GLU245VAL
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs137852279,
|
|
|
|
|
|
|
|
ClinVar: RCV000011398
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with hemophilia B (306900), Ludwig et al. (1992) identified an A-to-T transversion at nucleotide 30855, resulting in substitution of valine for glutamic acid-245. The variant was designated factor IX Monschau. </p>
|
|
</span>
|
|
</div>
|
|
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|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0097 HEMOPHILIA B BRANDENBURG</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, -26G-C, PROMOTER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2148352851,
|
|
|
|
|
|
|
|
ClinVar: RCV000011399
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Unlike other F9 promoter mutations which result in hemophilia B Leyden (see 306900) (e.g., 300746.0001), this promoter mutation, a G-to-C change at -26, is accompanied by a bleeding tendency that is not ameliorated after puberty (Reijnen et al., 1992). Reijnen et al. (1992) demonstrated that this mutation disrupted the binding of hepatocyte nuclear factor-4 (HNF4; 600281), a member of the steroid hormone receptor superfamily of transcription factors, which normally binds at nucleotides -34 to -10. Whereas HNF4 transactivated the wildtype promoter sequence in liver and nonliver (e.g., HeLa) cell types, it did not at all transactivate the -26 mutated promoter. </p><p>Crossley et al. (1992) provided an explanation for why the -20 promoter mutation shows recovery at puberty and the -26 Brandenburg mutation does not. Both mutations impair transcription by disrupting the binding site for the liver-enriched transcription factor LF-A1/HNF4. The -26 but not the -20 mutation also disrupts an androgen-responsive element, which overlaps the LF-A1/HNF4 site. This explains the failure of improvement in -26 patients. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0098 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ALU INSERTION, EX5
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe hemophilia B (306900), Vidaud et al. (1993) discovered a de novo insertion of a human-specific Alu repeat element within exon 5 of the F9 gene. The element interrupted the reading frame of the mature factor IX at glutamic acid 96 resulting in a stop codon within the inserted sequence. The Alu repeat was 322 bp long and was thought to have been inserted through retroposition. Insertional mutagenesis involving an Alu element has been reported in type I neurofibromatosis (162200.0001) and in gyrate atrophy (258870.0023). The involvement of Alu elements in gene deletion through homologous recombination and unequal crossing-over has been demonstrated in familial hypercholesterolemia (e.g., 143890.0029) and ADA deficiency (102700.0008). Also see Vidaud et al. (1989). </p><p>Note: This allelic variant was previously incorrectly in OMIM as EX51INS in 300746.0080.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0099 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HEMB, ILE-30ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906480,
|
|
|
|
|
|
|
|
ClinVar: RCV000011401
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Among the many mutations of the F9 gene described in hemophilia B (306900) (Giannelli et al., 1992), the density of amino acid substitutions in the domains coded by the different exons is similar, except for exon 'a' where it is much lower. Exon 'a' codes for the predomain of the signal peptide that is necessary for the transport of factor IX to the endoplasmic reticulum and for its secretion. Comparison of the signal peptide of secreted proteins shows lack of conservation of the primary amino acid sequence, and the only constant features are the presence of a charged residue at the amino end and a core of 8-12 hydrophobic residues. In a patient with severe, antigen-negative hemophilia B, Green et al. (1993) found an A-to-T transversion causing substitution of isoleucine by asparagine at position -30. This change disrupted the hydrophobic core of the prepeptide, a feature required for secretion. Thus, hemophilia in this patient was caused by failure to secrete factor IX from the hepatocytes. Only one other amino acid substitution had been reported in the prepeptide of factor IX; a cys-to-arg mutation at position -19 affecting the cleavage site between the pre- and propeptide (cys-19/thr-18) caused mild hemophilia (Bottema et al., 1991) (300746.0100). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0100 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HEMB, CYS-19ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906481,
|
|
|
|
|
|
|
|
ClinVar: RCV000011402, RCV001851793
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 300746.0099.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0101 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, VAL373GLU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852280,
|
|
|
|
|
|
|
|
ClinVar: RCV000011403
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Aguilar-Martinez et al. (1994) identified a val373-to-glu mutation in a 40-year-old man in whom the diagnosis of hemophilia (306900) was made at the age of 4 and who had been suffering hemarthrosis since the age of 13. A first cousin was affected. The mutation was located in the serine protease catalytic domain of the F9 gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0102 WARFARIN SENSITIVITY, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ALA37THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs367569299,
|
|
|
|
|
|
gnomAD: rs367569299,
|
|
|
|
|
|
ClinVar: RCV000990955, RCV001815016, RCV003117663
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Pezeshkpoor et al. (2018) noted that ala-10thr (A-10T) is the legacy designation for ala37-to-thr (A37T). The A37T designation includes the F9 signal sequence. </p><p>The propeptide sequences of the vitamin K-dependent clotting factors serve as a recognition site for the enzyme gamma-glutamyl carboxylase (137167), which catalyzes the carboxylation of glutamic acid residues in the amino terminus of the mature protein. Chu et al. (1996) described a mutation in the propeptide of factor IX that resulted in warfarin sensitivity (301052) because of reduced affinity of the carboxylase for the factor IX precursor. The patient was a 49-year-old with a congenital bicuspid aortic valve with accompanying aortic stenosis and regurgitation. After insertion of an artificial valve, he had bleeding complications when he was given warfarin for anticoagulation. The patient's family history was negative for bleeding diatheses. The patient had a factor IX activity level of more than 100% when not receiving warfarin and less than 1% when receiving warfarin, at a point where other vitamin K-dependent factors were at 30 to 40% activity levels. Direct sequence analysis of amplified genomic DNA from all 8 exons and exon-intron junctions showed a G-to-A transition at nucleotide 6346 resulting in an alanine-to-threonine change at residue -10 in the propeptide. To define the mechanism by which the mutation resulted in warfarin sensitivity, they analyzed wildtype and mutant recombinant peptides in an in vitro carboxylation reaction. The peptides that were analyzed included the wildtype sequence of F9, the ala-10thr sequence, and the ala-10gly substitution which reflects the sequence in bone gamma-carboxyglutamic acid protein (112260). Measurement of carbon dioxide incorporation at a range of peptide concentrations demonstrated about twice normal V(max) values for both A-10T and A-10G, whereas K(m) values showed a 33-fold difference between wildtype and the variants. These studies delineated a novel mechanism for warfarin sensitivity and explained the observation that bone gamma-carboxyglutamic acid protein is more sensitive to warfarin than the coagulation proteins. </p><p>Pezeshkpoor et al. (2018) reported that 11 patients with X-linked warfarin sensitivity, including 6 patients previously by Oldenburg et al. (2001), were found to have an A37T mutation in exon 2 of the F9 gene. The mutation, which occurs in a highly conserved region of the protein, was not identified in 1,834 female and 135 male healthy blood donors from different regions throughout Europe. Expression of F9 containing the A37T mutation in HEK293T cells resulted in a reduction in the FIX:C ratio and a reduced half maximal inhibitory concentration (IC50) for warfarin compared to HEK293T cells transfected with wildtype F9. This indicated a sensitivity to warfarin conferred by the A37T mutation. </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>.0103 WARFARIN SENSITIVITY, X-LINKED</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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F9, ALA37VAL
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<br />
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ClinVar: RCV000011406
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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>Pezeshkpoor et al. (2018) noted that ala-10val (A10V) is the legacy designation for ala37-to-val (A37V). The A37V designation includes the signal sequence. </p><p>Oldenburg et al. (1997) reported 3 patients in whom mutations in the factor IX propeptide was found to cause severe bleeding during coumarin therapy (301052). Strikingly, the bleeding occurred within the therapeutic ranges of the prothrombin time (PT) and international normalized ratio (INR). In all 3 patients, coumarin therapy caused an unusually selective decrease of factor IX activity to levels below 1 to 3%. Upon withdrawal of coumarin, factor IX levels increased to subnormal or normal values of 55, 85 and 125%, respectively. In 1 patient the ala-10-to-thr mutation (300746.0102) was found; in 2 patients the missense mutation affecting the ala-10 residue was ala (GCC) to val (GTC). The mutation in the propeptide at a position that is essential for the carboxylase recognition site causes a reduced affinity of the carboxylase enzyme to the propeptide. This effect leads to an impaired carboxylase epoxidase reaction that is decisively triggered by the vitamin K concentration. </p><p>Pezeshkpoor et al. (2018) reported that 7 patients with X-linked warfarin sensitivity, including 5 patients previously reported by Oldenburg et al. (2001), were found to have an A37V mutation in exon 2 of the F9 gene. The mutation, which occurs in a highly conserved region of the protein, was not identified in 1,834 female and 135 male healthy blood donors from different regions throughout Europe. Expression of F9 containing the A37V mutation in HEK293T cells resulted in a reduction in the FIX:C ratio and a reduced half maximal inhibitory concentration (IC50) for warfarin compared to HEK293T cells transfected with wildtype F9. This indicated a sensitivity to warfarin conferred by the A37V mutation. </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>.0104 HEMOPHILIA B</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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F9, ALA351PRO
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<br />
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SNP: rs137852281,
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ClinVar: RCV000011407
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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>Chan et al. (1998) found that a 20-year-old female student with mild hemophilia B (306900) was heterozygous for a mutation in codon 351 of the F9 gene: GCT (ala) was converted to CCT (pro). She had inherited the mutation from her carrier mother. Analysis of the methyl-sensitive HpaII sites at the 5-prime end of the hypoxanthine phosphoribosyltransferase gene (HPRT; 308000) showed that skewed inactivation of the X chromosome carrying her normal F9 gene accounted for the hemophilia 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">
|
|
<strong>.0105 HEMOPHILIA B</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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F9, 17747G-A
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<br />
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ClinVar: RCV000011408
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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>Drost et al. (2000) demonstrated that nucleotide 17747 of the F9 gene is a mutation hotspot for hemophilia B (306900) in all Latin American population samples but not in other populations. Two substitutions were observed, G-A and G-C (300746.0106). The authors suggested that this was the first evidence of population-specific effects on germline mutation that causes human genetic disease. </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>.0106 HEMOPHILIA B</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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F9, 17747G-C
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<br />
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ClinVar: RCV000011405
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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>See (300746.0105) and Drost et al. (2000). </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>.0107 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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|
F9, IVS3DS, T-C, +2
|
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<br />
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|
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SNP: rs587776735,
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|
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|
|
ClinVar: RCV000011409
|
|
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</span>
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|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a woman with moderately severe hemophilia B (306900), Costa et al. (2000) found a T-to-C transition at position +2 in the 5-prime splice site of intron 3 (6704T-C) and an ile344-to-thr missense mutation (306900.0108). The splice site mutation came from the mother who was a somatic mosaic; the missense mutation appeared to be a de novo mutation from the father. </p>
|
|
</span>
|
|
</div>
|
|
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0108 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ILE344THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906482,
|
|
|
|
|
|
|
|
ClinVar: RCV000011410
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 300746.0107 and Costa et al. (2000). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0109 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, CYS206SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267606792,
|
|
|
|
|
|
|
|
ClinVar: RCV000011411
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Taylor et al. (1992) found that the causative mutation in the first reported patient with Christmas disease (306900) (Biggs et al., 1952) was a cys206-to-ser change in the F9 gene. The patient died at the age of 46 years from acquired immunodeficiency syndrome, contracted through treatment with blood products (Giangrande, 2003). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0110 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, 2-BP DEL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776736,
|
|
|
|
|
|
|
|
ClinVar: RCV000011412
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Cutler et al. (2004) described a family in which the maternal grandfather of a severely affected infant with hemophilia B (306900) was a somatic and germline mosaic and had very mild factor IX deficiency. The maternal grandfather was apparently a somatic and germline mosaic for the family mutation, a 2-bp deletion (AG within codons 134-135) in the F9 gene causing a frameshift mutation and the creation of a premature termination sequence in exon 6 at codon 141. One daughter, the mother of the proband, was a carrier of the mutation; the other daughter, was not a carrier. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0111 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ARG338PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852283,
|
|
|
|
|
|
|
|
ClinVar: RCV000011413
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with a mild form of hemophilia B (306900), Ketterling et al. (1994) identified a G-to-C transversion in the F9 gene, resulting in an arg338-to-pro (R338P) substitution. There was 16% residual F9 activity. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0112 THROMBOPHILIA, X-LINKED, DUE TO FACTOR IX DEFECT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, ARG338LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852283,
|
|
|
|
|
|
|
|
ClinVar: RCV000011414, RCV000119810
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This mutation is known as factor IX Padua.</p><p>In a 21-year-old Italian man with thrombophilia and a deep venous thrombosis in the right leg (300807), Simioni et al. (2009) identified a hemizygous 31134G-T transversion in exon 8 of the F9 gene, resulting in an arg338-to-leu (R338L) substitution. Coagulation studies showed that he had normal levels of F9 antigen, but very high levels of F9 activity (776% of control values). His 11-year-old brother and mother, who were hemizygous and heterozygous for the mutation, respectively, also had normal F9 antigen levels and increased F9 activity levels (551% and 337%, respectively). The mutation was not found in 200 control individuals or in 200 patients with documented thromboembolism. In vitro functional expression studies showed that the mutant F9 had 8-fold increased activity compared to wildtype, consistent with a gain of function. The affected residue is important for binding to F10 (see 227600), and the R338L substitution apparently increases the efficiency of this binding. Simioni et al. (2009) noted that another mutation at this residue, R338P (300746.0111), results in hemophilia B (306900). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0113 HEMOPHILIA B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
F9, IVS3, A-G, -3
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs398122990,
|
|
|
|
|
|
|
|
ClinVar: RCV000077844, RCV001072034
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Although the X-linked blood disorder known as the 'royal disease' transmitted from Queen Victoria (1819-1901) to European royal families had been known to be a form of hemophilia, its molecular basis had not been established. In the remains of the Russian Empress Alexandra, granddaughter of Queen Victoria, and her son, Crown Prince Alexei, Rogaev et al. (2009) identified an A-to-G transition at the -3 position of intron 3 of the F9 gene. The mutation activated a cryptic splice acceptor site, shifting the open reading frame of the F9 mRNA and leading to a premature stop codon. The mutation was also identified in one of Alexei's sisters, presumed to be Anastasia. The identification of this mutation in the F9 gene allowed the recognition of the 'royal disease' as a severe form of hemophilia B, also known as 'Christmas disease' (306900). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
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|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Anson et al. (1985); Bertina et al. (1979); Bertina and van der
|
|
Linden (1982); Bertina and Veltkamp (1978); Bottema et al. (1990);
|
|
Bottema et al. (1989); Braunstein et al. (1981); Bray and Thompson
|
|
(1986); Brinkhous et al. (1973); Camerino et al. (1985); Chan et al.
|
|
(1989); Chen et al. (1989); Choo et al. (1987); Drayna et al. (1984);
|
|
Giannelli et al. (1999); Graham et al. (1962); Gray and Winship
|
|
(1989); Green et al. (1999); Kling et al. (1992); Koeberl et al.
|
|
(1990); Koeberl et al. (1990); Liebman et al. (1985); Little et al.
|
|
(1992); Mandalaki et al. (1986); Mattei et al. (1985); Smith (1985);
|
|
Spitzer et al. (1988); Thompson (1987); Usharani et al. (1985);
|
|
Vidaud et al. (1993); Vogel and Motulsky (1986); Wang et al. (1997);
|
|
Yoshioka et al. (1986)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
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|
|
|
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Aguilar-Martinez, P., Romey, M.-C., Gris, J.-C., Schved, J.-F., Demaille, J., Claustres, M.
|
|
<strong>A novel mutation (val373-to-glu) in the catalytic domain of factor IX, resulting in moderately/severe hemophilia B in a southern French patient.</strong>
|
|
Hum. Mutat. 3: 156-158, 1994.
|
|
|
|
|
|
[PubMed: 8199596]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1380030211]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Anson, D. S., Austen, D. E. G., Brownlee, G. G.
|
|
<strong>Expression of active human clotting factor IX from recombinant DNA clones in mammalian cells.</strong>
|
|
Nature 315: 683-685, 1985.
|
|
|
|
|
|
[PubMed: 2989700]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/315683a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Anson, D. S., Blake, D. J., Winship, P. R., Birnbaum, D., Brownlee, G. G.
|
|
<strong>Nullisomic deletion of the mcf.2 transforming gene in two haemophilia B patients.</strong>
|
|
EMBO J. 7: 2795-2799, 1988.
|
|
|
|
|
|
[PubMed: 2846283]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1988.tb03134.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Anson, D. S., Choo, K. H., Rees, D. J. G., Giannelli, F., Gould, K., Huddleston, J. A., Brownlee, G. G.
|
|
<strong>The gene structure of human anti-haemophilic factor IX.</strong>
|
|
EMBO J. 3: 1053-1060, 1984.
|
|
|
|
|
|
[PubMed: 6329734]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1984.tb01926.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Attree, O., Vidaud, D., Vidaud, M., Amselem, S., Lavergne, J.-M., Goossens, M.
|
|
<strong>Mutations in the catalytic domain of human coagulation factor IX: rapid characterization by direct genomic sequencing of DNA fragments displaying an altered melting behavior.</strong>
|
|
Genomics 4: 266-272, 1989.
|
|
|
|
|
|
[PubMed: 2714791]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(89)90330-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Attree, O., Vidaud, M., Vidaud, D., Lavergne, J. M., Goossens, M.
|
|
<strong>New strategies for rapid detection and characterization of mutations in hemophilia B. (Abstract)</strong>
|
|
Thromb. Haemost. 62: 8, 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bentley, A. K., Rees, D. J. G., Rizza, C., Brownlee, G. G.
|
|
<strong>Defective propeptide processing of blood clotting factor IX caused by mutation of arginine to glutamine at position -4.</strong>
|
|
Cell 45: 343-348, 1986.
|
|
|
|
|
|
[PubMed: 3009023]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(86)90319-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bernardi, F., Del Senno, L., Barbieri, R., Buzzoni, D., Gambari, R., Marchetti, G., Conconi, F., Panicucci, F., Positano, M., Pitruzzello, S.
|
|
<strong>Gene deletion in an Italian haemophilia B subject.</strong>
|
|
J. Med. Genet. 22: 305-307, 1985.
|
|
|
|
|
|
[PubMed: 4045960]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.22.4.305]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bertina, R. M., Briet, E., Veltkamp, J. J.
|
|
<strong>Variants of vitamin K dependent coagulation factors. (Editorial)</strong>
|
|
Acta Haemat. 62: 1-3, 1979.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bertina, R. M., van der Linden, I. K., Mannucci, P. M., Reinalda-Poot, H. H., Cupers, R., Poort, S. R., Reitsma, P. H.
|
|
<strong>Mutations in haemophilia B-M occur at the 180arg-to-val activation site or in the catalytic domain. (Abstract)</strong>
|
|
Thromb. Haemost. 62: 203, 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bertina, R. M., van der Linden, I. K., Mannucci, P. M., Reinalda-Poot, H. H., Cupers, R., Poort, S. R., Reitsma, P. H.
|
|
<strong>Mutations in hemophilia B(m) occur at the arg(180)-to-val activation site or in the catalytic domain of factor IX.</strong>
|
|
J. Biol. Chem. 265: 10876-10883, 1990.
|
|
|
|
|
|
[PubMed: 2162822]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bertina, R. M., van der Linden, I. K.
|
|
<strong>Factor IX Deventer--evidence for the heterogeneity of hemophilia B(M).</strong>
|
|
Thromb. Haemost. 47: 136-140, 1982.
|
|
|
|
|
|
[PubMed: 7101232]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bertina, R. M., Veltkamp, J. J.
|
|
<strong>The abnormal factor IX of hemophilia B+ variants.</strong>
|
|
Thromb. Haemost. 40: 335-349, 1978.
|
|
|
|
|
|
[PubMed: 734633]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bertina, R. M.
|
|
<strong>Personal Communication.</strong>
|
|
Leiden, The Netherlands 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bezemer, I. D., Arellano, A. R., Tong, C. H., Rowland, C. M., Ireland, H. A., Bauer, K. A., Catanese, J., Reitsma, P. H., Doggen, C. J. M., Devlin, J. J., Rosendaal, F. R., Bare, L. A.
|
|
<strong>F9 Malmo, factor IX and deep vein thrombosis.</strong>
|
|
Haematologica 94: 693-699, 2009.
|
|
|
|
|
|
[PubMed: 19286883]
|
|
|
|
|
|
[Full Text: https://doi.org/10.3324/haematol.2008.003020]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bezemer, I. D., Bare, L. A., Doggen, C. J. M., Arellano, A. R., Tong, C., Rowland, C. M., Catanese, J., Young, B. A., Reitsma, P. H., Devlin, J. J., Rosendaal, F. R.
|
|
<strong>Gene variants associated with deep vein thrombosis.</strong>
|
|
JAMA 299: 1306-1314, 2008.
|
|
|
|
|
|
[PubMed: 18349091]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/jama.299.11.1306]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Biggs, R., Douglas, A. S., Macfarlane, R. G., Dacie, J. V., Pitney, W. R., Merskey, C., O'Brien, J. R.
|
|
<strong>Christmas disease: a condition previously mistaken for haemophilia.</strong>
|
|
Brit. Med. J. 2: 1378-1382, 1952.
|
|
|
|
|
|
[PubMed: 12997790]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/bmj.2.4799.1378]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bottema, C. D. K., Bottema, M. J., Ketterling, R. P., Yoon, H.-S., Janco, R. L., Phillips, J. A., III, Sommer, S. S.
|
|
<strong>Why does the human factor IX gene have a G+C content of 40%?</strong>
|
|
Am. J. Hum. Genet. 49: 839-850, 1991.
|
|
|
|
|
|
[PubMed: 1897528]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bottema, C. D. K., Ketterling, R. P., Ii, S., Yoon, H.-S., Phillips, J. A., III, Sommer, S. S.
|
|
<strong>Missense mutations and evolutionary conservation of amino acids: evidence that many of the amino acids in factor IX function as 'spacer' elements.</strong>
|
|
Am. J. Hum. Genet. 49: 820-838, 1991.
|
|
|
|
|
|
[PubMed: 1680287]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bottema, C. D. K., Ketterling, R. P., Vielhaber, E., Yoon, H.-S., Gostout, B., Jacobson, D. P., Shapiro, A., Sommer, S. S.
|
|
<strong>The pattern of spontaneous germ-line mutation: relative rates of mutation at or near CpG dinucleotides in the factor IX gene.</strong>
|
|
Hum. Genet. 91: 496-503, 1993.
|
|
|
|
|
|
[PubMed: 8314564]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00217779]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bottema, C. D. K., Ketterling, R. P., Yoon, H.-S., Sommer, S. S.
|
|
<strong>The pattern of factor IX germ-line mutation in Asians is similar to that of Caucasians.</strong>
|
|
Am. J. Hum. Genet. 47: 835-841, 1990.
|
|
|
|
|
|
[PubMed: 2220823]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bottema, C. D. K., Koeberl, D. D., Ketterling, R. P., Bowie, E. J. W., Taylor, S. A. M., Lillicrap, D., Shapiro, A., Gilchrist, G., Sommer, S. S.
|
|
<strong>A past mutation at isoleucine-397 is now a common cause of moderate/mild haemophilia B.</strong>
|
|
Brit. J. Haemat. 75: 212-216, 1990.
|
|
|
|
|
|
[PubMed: 2372508]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1990.tb02651.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bottema, C. D. K., Koeberl, D. D., Ketterling, R. P., Lillicrap, D. P., Bridges, P., Sommer, S. S.
|
|
<strong>The molecular pathology of hemophilia B is a mirror of the pattern of recent germline mutations in humans. (Abstract)</strong>
|
|
Blood 74: 252A, 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bottema, C. D. K., Koeberl, D. D., Sommer, S. S.
|
|
<strong>Direct carrier testing in 14 families with haemophilia B.</strong>
|
|
Lancet 334: 526-529, 1989. Note: Originally Volume 2.
|
|
|
|
|
|
[PubMed: 2570235]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(89)90653-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Boyd, Y., Buckle, V. J., Munro, E. A., Choo, K. H., Migeon, B. R., Craig, I. W.
|
|
<strong>Assignment of the haemophilia B (factor IX) locus to the q26-qter region of the X chromosome.</strong>
|
|
Ann. Hum. Genet. 48: 145-152, 1984.
|
|
|
|
|
|
[PubMed: 6331274]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1469-1809.1984.tb01009.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Braunstein, K. M., Noyes, C. M., Griffith, M. J., Lundblad, R. L., Roberts, H. R.
|
|
<strong>Characterization of the defect in activation of factor IX(Chapel Hill) by human factor XIa.</strong>
|
|
J. Clin. Invest. 68: 1420-1426, 1981.
|
|
|
|
|
|
[PubMed: 6976355]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/jci110393]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bray, G. L., Thompson, A. R.
|
|
<strong>Partial factor IX protein in a pedigree with hemophilia B due to a partial gene deletion.</strong>
|
|
J. Clin. Invest. 77: 1194-1200, 1986.
|
|
|
|
|
|
[PubMed: 3514676]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI112421]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Briet, E., Bertina, R. M., van Tilburg, N. H., Veltkamp, J. J.
|
|
<strong>Hemophilia B Leyden: a sex-linked hereditary disorder that improves after puberty.</strong>
|
|
New Eng. J. Med. 306: 788-790, 1982.
|
|
|
|
|
|
[PubMed: 7062952]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198204013061306]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brinkhous, K. M., Davis, P. D., Graham, J. B., Dodds, W. J.
|
|
<strong>Expression and linkage of genes for X-linked hemophilias A and B in the dog.</strong>
|
|
Blood 41: 577-585, 1973.
|
|
|
|
|
|
[PubMed: 4688873]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brooks, M. B., Gu, W., Barnas, J. L., Ray, J., Ray, K.
|
|
<strong>A line 1 insertion in the factor IX gene segregates with mild hemophilia B in dogs.</strong>
|
|
Mammalian Genome 14: 788-795, 2003.
|
|
|
|
|
|
[PubMed: 14722728]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00335-003-2290-z]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brownlee, G. G.
|
|
<strong>Haemophilia B: a review of patient defects, diagnosis with gene probes and prospects for gene therapy.</strong>
|
|
Recent Adv. Haemat. 5: 251-265, 1988.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Camerino, G., Grzeschik, K. H., Jaye, M., de la Salle, H., Tolstoshev, P., Lecocq, J. P., Heilig, R., Mandel, J. L.
|
|
<strong>Regional localization on the human X chromosome and polymorphism of the coagulation factor IX gene (hemophilia B locus).</strong>
|
|
Proc. Nat. Acad. Sci. 81: 498-502, 1984.
|
|
|
|
|
|
[PubMed: 6320191]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.81.2.498]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Camerino, G., Mattei, M. G., Mattei, J. F., Jaye, M., Mandel, J. L.
|
|
<strong>Genetics of the fragile X-mental retardation syndrome: close linkage to hemophilia B and transmission through a normal male.</strong>
|
|
Nature 306: 701-704, 1983.
|
|
|
|
|
|
[PubMed: 6689201]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/306701a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Camerino, G., Oberle, I., Drayna, D., Mandel, J. L.
|
|
<strong>A new MspI restriction fragment length polymorphism in the hemophilia B locus.</strong>
|
|
Hum. Genet. 71: 79-81, 1985.
|
|
|
|
|
|
[PubMed: 2411652]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00295673]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chan, V., Chan, T. K., Tong, T. M. F., 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: 2510835]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chan, V., Chan, V. W. Y., Yip, B., Chim, C. S., Chan, T. K.
|
|
<strong>Hemophilia B in a female carrier due to skewed inactivation of the normal X-chromosome.</strong>
|
|
Am. J. Hemat. 58: 72-76, 1998.
|
|
|
|
|
|
[PubMed: 9590153]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1096-8652(199805)58:1<72::aid-ajh13>3.0.co;2-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chance, P. F., Dyer, K. A., Kurachi, K., Yoshitake, S., Ropers, H.-H., Wieacker, P., Gartler, S. M.
|
|
<strong>Regional localization of the human factor IX gene by molecular hybridization.</strong>
|
|
Hum. Genet. 65: 207-208, 1983.
|
|
|
|
|
|
[PubMed: 6686210]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00286666]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, S.-H., Scott, C. R., Edson, J. R., Kurachi, K.
|
|
<strong>An insertion within the factor IX gene: hemophilia B(El Salvador).</strong>
|
|
Am. J. Hum. Genet. 42: 581-584, 1988.
|
|
|
|
|
|
[PubMed: 2831715]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, S.-H., Scott, C. R., Schoof, J., Lovrien, E. W., Kurachi, K.
|
|
<strong>Factor IX(Portland): a nonsense mutation (CGA to TGA) resulting in hemophilia B.</strong>
|
|
Am. J. Hum. Genet. 44: 567-569, 1989.
|
|
|
|
|
|
[PubMed: 2929599]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, S.-H., Thompson, A. R., Zhang, M., Scott, C. R.
|
|
<strong>Three point mutations in the factor IX genes of five hemophilia B patients: identification strategy using localization by altered epitopes in their hemophilic proteins.</strong>
|
|
J. Clin. Invest. 84: 113-118, 1989.
|
|
|
|
|
|
[PubMed: 2472424]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI114130]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, S.-H., Thompson, A. R.
|
|
<strong>Personal Communication.</strong>
|
|
Seattle, Wash. 11/1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, S.-H., Yoshitake, S., Chance, P. F., Bray, G. L., Thompson, A. R., Scott, C. R., Kurachi, K.
|
|
<strong>An intragenic deletion of the factor IX gene in a family with hemophilia B.</strong>
|
|
J. Clin. Invest. 76: 2161-2164, 1985.
|
|
|
|
|
|
[PubMed: 3001143]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI112222]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, S.-H., Zhang, M., Lovrien, E. W., Scott, C. R., Thompson, A. R.
|
|
<strong>CG dinucleotide transitions in the factor IX gene account for about half of the point mutations in hemophilia B patients: a Seattle series.</strong>
|
|
Hum. Genet. 87: 177-182, 1991.
|
|
|
|
|
|
[PubMed: 2066105]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00204177]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Choo, K. H., Gould, K. G., Rees, D. J. G., Brownlee, G. G.
|
|
<strong>Molecular cloning of the gene for human anti-haemophilic factor IX.</strong>
|
|
Nature 299: 178-180, 1982.
|
|
|
|
|
|
[PubMed: 6287289]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/299178a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Choo, K. H., Raphael, K., McAdam, W., Peterson, M. G.
|
|
<strong>Expression of active human blood clotting factor IX in transgenic mice: use of a cDNA with complete mRNA sequence.</strong>
|
|
Nucleic Acids Res. 15: 871-884, 1987.
|
|
|
|
|
|
[PubMed: 3029708]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/15.3.871]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chu, K., Wu, S.-M., Stanley, T., Stafford, D. W., High, K. A.
|
|
<strong>A mutation in the propeptide of factor IX leads to warfarin sensitivity by a novel mechanism.</strong>
|
|
J. Clin. Invest. 98: 1619-1625, 1996.
|
|
|
|
|
|
[PubMed: 8833911]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI118956]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cooper, D. N., Krawczak, M.
|
|
<strong>The mutational spectrum of single base-pair substitutions causing human genetic disease: patterns and predictions.</strong>
|
|
Hum. Genet. 85: 55-74, 1990.
|
|
|
|
|
|
[PubMed: 2192981]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00276326]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Costa, J.-M., Vidaud, D., Laurendeau, I., Vidaud, M., Fressinaud, E., Moisan, J.-P., David, A., Meyer, D., Lavergne, J.-M.
|
|
<strong>Somatic mosaicism and compound heterozygosity in female hemophilia B.</strong>
|
|
Blood 96: 1585-1587, 2000.
|
|
|
|
|
|
[PubMed: 10942410]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Crossley, M., Brownlee, G. G.
|
|
<strong>Disruption of a C/EBP binding site in the factor IX promoter is associated with haemophilia B.</strong>
|
|
Nature 345: 444-446, 1990.
|
|
|
|
|
|
[PubMed: 2342576]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/345444a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Crossley, M., Ludwig, M., Stowell, K. M., De Vos, P., Olek, K., Brownlee, G. G.
|
|
<strong>Recovery from hemophilia B Leyden: an androgen-responsive element in the factor IX promoter.</strong>
|
|
Science 257: 377-379, 1992.
|
|
|
|
|
|
[PubMed: 1631558]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1631558]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Crossley, M., Winship, P. R., Austen, D. E. G., Rizza, C. R., Brownlee, G. G.
|
|
<strong>A less severe form of haemophilia B Leyden.</strong>
|
|
Nucleic Acids Res. 18: 4633, 1990.
|
|
|
|
|
|
[PubMed: 2388855]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/18.15.4633]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Crossley, P. M., Winship, P. R., Black, A., Rizza, C. R., Brownlee, G. G.
|
|
<strong>Unusual case of haemophilia B. (Letter)</strong>
|
|
Lancet 333: 960 only, 1989. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: 2565449]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(89)92540-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cutler, J. A., Mitchell, M. J., Smith, M. P., Savidge, G. F.
|
|
<strong>Germline mosaicism resulting in the transmission of severe hemophilia B from a grandfather with a mild deficiency.</strong>
|
|
Am. J. Med. Genet. 129A: 13-15, 2004.
|
|
|
|
|
|
[PubMed: 15266608]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.30162]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Davie, E. W., Fujikawa, K.
|
|
<strong>Basic mechanisms in blood coagulation.</strong>
|
|
Ann. Rev. Biochem. 44: 799-829, 1975.
|
|
|
|
|
|
[PubMed: 237463]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1146/annurev.bi.44.070175.004055]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Davis, L. M., McGraw, R. A., Graham, J. B., Roberts, H. R., Stafford, D. W.
|
|
<strong>Identification of the genetic defect in factor IX (Alabama): DNA sequence analysis reveals a gly substitution for asp(46). (Abstract)</strong>
|
|
Blood 64 (suppl.): 262a, 1984.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Davis, L. M., McGraw, R. A., Ware, J. L., Roberts, H. R., Stafford, D. W.
|
|
<strong>Factor IX (Alabama): a point mutation in a clotting protein results in hemophilia B.</strong>
|
|
Blood 69: 140-143, 1987.
|
|
|
|
|
|
[PubMed: 3790720]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Denton, P. H., Fowlkes, D. M., Lord, S. T., Reisner, H. M.
|
|
<strong>Hemophilia B Durham: a mutation in the first EGF-like domain of factor IX that is characterized by polymerase chain reaction.</strong>
|
|
Blood 72: 1407-1411, 1988.
|
|
|
|
|
|
[PubMed: 3262389]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Diuguid, D. L., Rabiet, M. J., Furie, B. C., Liebman, H. A., Furie, B.
|
|
<strong>Molecular basis of hemophilia B: a defective enzyme due to an unprocessed propeptide is caused by a point mutation in the factor IX precursor.</strong>
|
|
Proc. Nat. Acad. Sci. 83: 5803-5807, 1986.
|
|
|
|
|
|
[PubMed: 3461460]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.83.16.5803]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Drayna, D., Davies, K., Hartley, D., Mandel, J.-L., Camerino, G., Williamson, R., White, R.
|
|
<strong>Genetic mapping of the human X chromosome by using restriction fragment length polymorphisms.</strong>
|
|
Proc. Nat. Acad. Sci. 81: 2836-2839, 1984.
|
|
|
|
|
|
[PubMed: 6326147]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.81.9.2836]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Drost, J. B., Scaringe, W. A., Jaloma-Cruz, A. R., Li, X., Ossa, D. F., Kasper, C. K., Sommer, S. S.
|
|
<strong>Novel hotspot detector software reveals a non-CpG hotspot of germline mutation in the factor IX gene (F9) in Latin Americans.</strong>
|
|
Hum. Mutat. 16: 203-210, 2000.
|
|
|
|
|
|
[PubMed: 10980527]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/1098-1004(200009)16:3<203::AID-HUMU3>3.0.CO;2-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fahner, J. B., Salier, J. P., Landa, L., Hirosawa, S., Lovrien, E. W., Kurachi, K.
|
|
<strong>Defective promoter structure in a human factor IX-Leyden. (Abstract)</strong>
|
|
Blood 72: 295A, 1988.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fujikawa, K., Coan, M. H., Enfield, D. L., Titani, K., Ericsson, L. H., Davie, E. W.
|
|
<strong>A comparison of bovine prothrombin, factor IX (Christmas factor), and factor X (Stuart factor).</strong>
|
|
Proc. Nat. Acad. Sci. 71: 427-430, 1974.
|
|
|
|
|
|
[PubMed: 4205592]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.71.2.427]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Geddes, V. A., Le Bonniec, B. F., Louie, G. V., Brayer, G. D., Thompson, A. R., MacGillivray, R. T. A.
|
|
<strong>A moderate form of hemophilia B is caused by a novel mutation in the protease domain of factor IX(Vancouver).</strong>
|
|
J. Biol. Chem. 264: 4689-4697, 1989.
|
|
|
|
|
|
[PubMed: 2494175]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Geddes, V. A., Louie, G. V., Brayer, G. D., MacGillivray, R. T. A.
|
|
<strong>Molecular basis of hemophilia B: identification of the defect in factor IX Vancouver. (Abstract)</strong>
|
|
Thromb. Haemost. 58 (suppl.): 294, 1987.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giangrande, P. L. F.
|
|
<strong>Historical review: six characters in search of an author: the history of the nomenclature of coagulation factors.</strong>
|
|
Brit. J. Haemat. 121: 703-712, 2003.
|
|
|
|
|
|
[PubMed: 12780784]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1365-2141.2003.04333.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Anagnostopoulos, T., Green, P. M.
|
|
<strong>Mutation rates in humans. II. Sporadic mutation-specific rates and rate of detrimental human mutations inferred from hemophilia B.</strong>
|
|
Am. J. Hum. Genet. 65: 1580-1587, 1999.
|
|
|
|
|
|
[PubMed: 10577911]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302652]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Choo, K. H., Rees, D. J. G., Boyd, Y., Rizza, C. R., Brownlee, G. G.
|
|
<strong>Gene deletions in patients with haemophilia B and anti-factor IX antibodies.</strong>
|
|
Nature 303: 181-182, 1983.
|
|
|
|
|
|
[PubMed: 6843667]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/303181a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Green, P. M., High, K. A., Sommer, S., Lillicrap, D. P., Ludwig, M., Olek, K., Reitsma, P. H., Goossens, M., Yoshioka, A., Brownlee, G. G.
|
|
<strong>Haemophilia B: database of point mutations and short additions and deletions--third edition, 1992.</strong>
|
|
Nucleic Acids Res. 20: 2027-2063, 1992.
|
|
|
|
|
|
[PubMed: 1598234]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/20.suppl.2027]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Green, P. M., High, K. A., Sommer, S., Poon, M.-C., Ludwig, M., Schwaab, R., Reitsma, P. H., Goossens, M., Yoshioka, A., Brownlee, G. G.
|
|
<strong>Haemophilia B: database of point mutations and short additions and deletions--fourth edition, 1993.</strong>
|
|
Nucleic Acids Res. 21: 3075-3087, 1993.
|
|
|
|
|
|
[PubMed: 8392713]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/21.13.3075]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Green, P. M., Sommer, S. S., Poon, M.-C., Ludwig, M., Schwaab, R., Reitsma, P. H., Goossens, M., Yoshioka, A., Brownlee, G. G.
|
|
<strong>Haemophilia B (sixth edition): a database of point mutations and short additions and deletions.</strong>
|
|
Nucleic Acids Res. 24: 103-118, 1996.
|
|
|
|
|
|
[PubMed: 8594556]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/24.1.103]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giannelli, F., Green, P. M., Sommer, S. S., Poon, M.-C., Ludwig, M., Schwaab, R., Reitsma, P. H., Goossens, M., Yoshioka, A., Figueiredo, M. S., Brownlee, G. G.
|
|
<strong>Haemophilia B: database of point mutations and short additions and deletions, 7th edition.</strong>
|
|
Nucleic Acids Res. 25: 133-135, 1997.
|
|
|
|
|
|
[PubMed: 9016521]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/25.1.133]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Graham, J. B., Lubahn, D. B., Lord, S. T., Kirshtein, J., Nilsson, I. M., Wallmark, A., Ljung, R., Frazier, L. D., Ware, J. L., Lin, S. W., Stafford, D. W., Bosco, J.
|
|
<strong>The Malmo polymorphism of coagulation factor IX, an immunologic polymorphism due to dimorphism of residue 148 that is in linkage disequilibrium with two other F.IX polymorphisms.</strong>
|
|
Am. J. Hum. Genet. 42: 573-580, 1988.
|
|
|
|
|
|
[PubMed: 2450455]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Graham, J. B., Tarleton, H. L., Race, R. R., Sanger, R.
|
|
<strong>A human double cross-over.</strong>
|
|
Nature 195: 834, 1962.
|
|
|
|
|
|
[PubMed: 13901025]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/195834a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gray, M. W., Winship, P. R.
|
|
<strong>CpG polymorphisms and haemophilia B. (Letter)</strong>
|
|
Lancet 334: 502-503, 1989. Note: Originally Volume 2.
|
|
|
|
|
|
[PubMed: 2570208]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(89)92111-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Green, P. M., Bentley, D. R., Mibashan, R. S., Nilsson, I. M., Giannelli, F.
|
|
<strong>Molecular pathology of haemophilia B.</strong>
|
|
EMBO J. 8: 1067-1072, 1989.
|
|
|
|
|
|
[PubMed: 2743975]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1989.tb03474.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Green, P. M., Mitchell, V. E., McGraw, A., Goldman, E., Giannelli, F.
|
|
<strong>Haemophilia B caused by a missense mutation in the prepeptide sequence of factor IX.</strong>
|
|
Hum. Mutat. 2: 103-107, 1993.
|
|
|
|
|
|
[PubMed: 8318985]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1380020207]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
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.
|
|
|
|
|
|
[PubMed: 1768766]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/00001721-199108000-00007]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Green, P. M., Montandon, A. J., Ljung, R., Nilsson, I. M., Giannelli, F.
|
|
<strong>Haplotype analysis of identical factor IX mutants using PCR.</strong>
|
|
Thromb. Haemost. 67: 66-69, 1992.
|
|
|
|
|
|
[PubMed: 1615486]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Green, P. M., Saad, S., Lewis, C. M., Giannelli, F.
|
|
<strong>Mutation rates in humans. I. Overall and sex-specific rates obtained from a population study of hemophilia B.</strong>
|
|
Am. J. Hum. Genet. 65: 1572-1579, 1999.
|
|
|
|
|
|
[PubMed: 10577910]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302651]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gu, W., Brooks, M., Catalfamo, J., Ray, J., Ray, K.
|
|
<strong>Two distinct mutations cause severe hemophilia B in two unrelated canine pedigrees.</strong>
|
|
Thromb. Haemost. 82: 1270-1275, 1999.
|
|
|
|
|
|
[PubMed: 10544912]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hassan, H. J., Leonardi, A., Guerriero, R., Chelucci, C., Cianetti, L., Ciavarella, N., Ranieri, P., Pilolli, D., Peschle, C.
|
|
<strong>Hemophilia B with inhibitor: molecular analysis of the subtotal deletion of the factor IX gene.</strong>
|
|
Blood 66: 728-730, 1985.
|
|
|
|
|
|
[PubMed: 2992643]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hirosawa, S., Fahner, J. B., Salier, J.-P., Wu, C.-T., Lovrien, E. W., Kurachi, K.
|
|
<strong>Structural and functional basis of the developmental regulation of human coagulation factor IX gene: factor IX Leyden.</strong>
|
|
Proc. Nat. Acad. Sci. 87: 4421-4425, 1990.
|
|
|
|
|
|
[PubMed: 2352926]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.87.12.4421]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hougie, C., Twomey, J. J.
|
|
<strong>Hemophilia B(M): a new type of factor-IX deficiency.</strong>
|
|
Lancet 289: 698-700, 1967. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: 4163943]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(67)92179-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Huang, M.-N., Kasper, C. K., Roberts, H. R., Stafford, D. W., High, K. A.
|
|
<strong>Molecular defect in factor IX(Hilo), a hemophilia B(m) variant: arg-to-gln at the carboxyterminal cleavage site of the activation peptide.</strong>
|
|
Blood 73: 718-721, 1989.
|
|
|
|
|
|
[PubMed: 2563663]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jagadeeswaran, P., Lavelle, D. E., Kaul, R., Mohandas, T., Warren, S. T.
|
|
<strong>Isolation and characterization of human factor IX cDNA: identification of Taq I polymorphism and regional assignment.</strong>
|
|
Somat. Cell Molec. Genet. 10: 465-473, 1984.
|
|
|
|
|
|
[PubMed: 6089357]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01534851]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kasper, C. K., Osterud, B., Minami, J. Y., Schonick, W., Rapaport, S. I.
|
|
<strong>Hemophilia B--characterization of genetic variants and detection of carriers.</strong>
|
|
Blood 50: 351-366, 1977.
|
|
|
|
|
|
[PubMed: 884315]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kazazian, H. H., Jr.
|
|
<strong>An estimated frequency of endogenous insertional mutations in humans.</strong>
|
|
Nature Genet. 22: 130 only, 1999.
|
|
|
|
|
|
[PubMed: 10369250]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/9638]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ketterling, R. P., Bottema, C. D. K., Koeberl, D. D., Ii, S., Sommer, S. S.
|
|
<strong>T-296-to-M, a common mutation causing mild hemophilia B in the Amish and others: founder effect, variability in factor IX activity assays, and rapid carrier detection.</strong>
|
|
Hum. Genet. 87: 333-337, 1991.
|
|
|
|
|
|
[PubMed: 1864609]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00200915]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ketterling, R. P., Vielhaber, E., Bottema, C. D. K., Schaid, D. J., Cohen, M. P., Sexauer, C. L., Sommer, S. S.
|
|
<strong>Germ-line origins of mutation in families with hemophilia B: the sex ratio varies with the type of mutation.</strong>
|
|
Am. J. Hum. Genet. 52: 152-166, 1993.
|
|
|
|
|
|
[PubMed: 8434583]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ketterling, R. P., Vielhaber, E. L., Lind, T. J., Thorland, E. C., Sommer, S. S.
|
|
<strong>The rates and patterns of deletions in the human factor IX gene.</strong>
|
|
Am. J. Hum. Genet. 54: 201-213, 1994.
|
|
|
|
|
|
[PubMed: 8304338]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ketterling, R. P., Vielhaber, E., Sommer, S. S.
|
|
<strong>The rates of G:C-to-T:A and G:C-to-C:G transversions at CpG dinucleotides in the human factor IX gene.</strong>
|
|
Am. J. Hum. Genet. 54: 831-835, 1994.
|
|
|
|
|
|
[PubMed: 8178822]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kling, S., Ljung, R., Sjorin, E., Montandon, J., Green, P., Giannelli, F., Nilsson, I. M.
|
|
<strong>Origin of mutation in sporadic cases of haemophilia-B.</strong>
|
|
Europ. J. Haemat. 48: 142-145, 1992.
|
|
|
|
|
|
[PubMed: 1348478]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1600-0609.1992.tb00585.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koeberl, D. D., Bottema, C. D. K., Buerstedde, J.-M., Sommer, S. S.
|
|
<strong>Functionally important regions of the factor IX gene have a low rate of polymorphism and a high rate of mutation in the dinucleotide CpG.</strong>
|
|
Am. J. Hum. Genet. 45: 448-457, 1989.
|
|
|
|
|
|
[PubMed: 2773937]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koeberl, D. D., Bottema, C. D. K., Ketterling, R. P., Bridge, P. J., Lillicrap, D. P., Sommer, S. S.
|
|
<strong>Mutations causing hemophilia B: direct estimate of the underlying rates of spontaneous germ-line transitions, transversions, and deletions in a human gene.</strong>
|
|
Am. J. Hum. Genet. 47: 202-217, 1990.
|
|
|
|
|
|
[PubMed: 2198809]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koeberl, D. D., Bottema, C. D. K., Sarkar, G., Ketterling, R. P., Chen, S.-H., Sommer, S. S.
|
|
<strong>Recurrent nonsense mutations at arginine residues cause severe hemophilia B in unrelated hemophiliacs.</strong>
|
|
Hum. Genet. 84: 387-390, 1990.
|
|
|
|
|
|
[PubMed: 1969838]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00195805]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koeberl, D. D., Bottema, C. D. K., Sommer, S. S.
|
|
<strong>Comparison of direct and indirect methods of carrier detection in an X-linked disease.</strong>
|
|
Am. J. Med. Genet. 35: 600-608, 1990.
|
|
|
|
|
|
[PubMed: 1970704]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320350435]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kundu, R. K., Sangiorgi, F., Wu, L.-Y., Kurachi, K., Anderson, W. F., Maxson, R., Gordon, E. M.
|
|
<strong>Targeted inactivation of the coagulation factor IX gene causes hemophilia B in mice.</strong>
|
|
Blood 92: 168-174, 1998.
|
|
|
|
|
|
[PubMed: 9639513]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kurachi, K., Davie, E. W.
|
|
<strong>Isolation and characterization of a cDNA coding for human factor IX.</strong>
|
|
Proc. Nat. Acad. Sci. 79: 6461-6464, 1982.
|
|
|
|
|
|
[PubMed: 6959130]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.79.21.6461]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kurachi, S., Deyashiki, Y., Takeshita, J., Kurachi, K.
|
|
<strong>Genetic mechanisms of age regulation of human blood coagulation factor IX.</strong>
|
|
Science 285: 739-743, 1999.
|
|
|
|
|
|
[PubMed: 10426997]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.285.5428.739]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kurachi, S., Huo, J. S., Ameri, A., Zhang, K., Yoshizawa, A. C., Kurachi, K.
|
|
<strong>An age-related homeostasis mechanism is essential for spontaneous amelioration of hemophilia B Leyden.</strong>
|
|
Proc. Nat. Acad. Sci. 106: 7921-7926, 2009.
|
|
|
|
|
|
[PubMed: 19416882]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0902191106]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lefkowitz, J. B., Monroe, D. M., Kasper, C. K., Roberts, H. R.
|
|
<strong>Comparison of the behavior of normal factor IX and the factor IX BM variant Hilo in the prothrombin time test using tissue factors from bovine, human, and rabbit sources.</strong>
|
|
Am. J. Hemat. 43: 177-182, 1993.
|
|
|
|
|
|
[PubMed: 8352232]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajh.2830430304]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Li, X., Scaringe, W. A., Hill, K. A., Roberts, S., Mengos, A., Careri, D., Pinto, M. T., Kasper, C. K., Sommer, S. S.
|
|
<strong>Frequency of recent retrotransposition events in the human factor IX gene.</strong>
|
|
Hum. Mutat. 17: 511-519, 2001.
|
|
|
|
|
|
[PubMed: 11385709]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1134]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Liddell, M. B., Peake, I. R., Taylor, S. A. M., Lillicrap, D. P., Giddings, J. C., Bloom, A. L.
|
|
<strong>Factor IX Cardiff: a variant factor IX protein that shows abnormal activation is caused by an arginine to cysteine substitution at position 145.</strong>
|
|
Brit. J. Haemat. 72: 556-560, 1989.
|
|
|
|
|
|
[PubMed: 2775660]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1989.tb04323.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Liebman, H. A., Limentani, S. A., Furie, B. C., Furie, B.
|
|
<strong>Immunoaffinity purification of factor IX (Christmas factor) by using conformation-specific antibodies directed against the factor IX-metal complex.</strong>
|
|
Proc. Nat. Acad. Sci. 82: 3879-3883, 1985.
|
|
|
|
|
|
[PubMed: 2408269]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.82.11.3879]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Little, R. D., Pilia, G., Johnson, S., D'Urso, M., Schlessinger, D.
|
|
<strong>Yeast artificial chromosomes spanning 8 megabases and 10-15 centimorgans of human cytogenetic band Xq26.</strong>
|
|
Proc. Nat. Acad. Sci. 89: 177-181, 1992.
|
|
|
|
|
|
[PubMed: 1729687]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.89.1.177]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ljung, R., Petrini, P., Tengborn, L., Sjorin, E.
|
|
<strong>Haemophilia B mutations in Sweden: a population-based study of mutational heterogeneity.</strong>
|
|
Brit. J. Haemat. 113: 81-86, 2001.
|
|
|
|
|
|
[PubMed: 11328285]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1365-2141.2001.02759.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lozier, B. N., Stanfield-Oakley, S. A., High, K. A.
|
|
<strong>Factor IX New London: a point mutation causing hemophilia B. (Abstract)</strong>
|
|
Thromb. Haemost. 62: 162, 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ludwig, M., Sabharwal, A. K., Brackmann, H. H., Olek, K., Smith, K. J., Birktoft, J. J., Bajaj, S. P.
|
|
<strong>Hemophilia B caused by five different nondeletion mutations in the protease domain of factor IX.</strong>
|
|
Blood 79: 1225-1232, 1992.
|
|
|
|
|
|
[PubMed: 1346975]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ludwig, M., Schwaab, R., Eigel, A., Horst, J., Egli, H., Brackmann, H.-H., Olek, K.
|
|
<strong>Identification of a single nucleotide C-to-T transition and five different deletions in patients with severe hemophilia B.</strong>
|
|
Am. J. Hum. Genet. 45: 115-122, 1989.
|
|
|
|
|
|
[PubMed: 2741941]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mandalaki, T., Louizou, C., Dimitriadou, C., Briet, E.
|
|
<strong>Haemophilia B Leyden in Greece.</strong>
|
|
Thromb. Haemost. 56: 340-342, 1986.
|
|
|
|
|
|
[PubMed: 3563965]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matsushita, T., Tanimoto, M., Yamamoto, K., Sugiura, I., Hamaguchi, M., Takamatsu, J., Saito, H.
|
|
<strong>Nucleotide sequence analysis of hemophilia B with the inhibitor phenotype. (Abstract)</strong>
|
|
Blood 74: 251A, 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mattei, M. G., Baeteman, M. A., Heilig, R., Oberle, I., Davies, K., Mandel, J. L., Mattei, J. F.
|
|
<strong>Localization by in situ hybridization of the coagulation factor IX gene and of two polymorphic DNA probes with respect to the fragile X site.</strong>
|
|
Hum. Genet. 69: 327-331, 1985.
|
|
|
|
|
|
[PubMed: 2985491]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00291650]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matthews, R. J., Anson, D. S., Peake, I. R., Bloom, A. L.
|
|
<strong>Heterogeneity of the factor IX locus in nine hemophilia B inhibitor patients.</strong>
|
|
J. Clin. Invest. 79: 746-753, 1987.
|
|
|
|
|
|
[PubMed: 3029178]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI112880]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matthews, R. J., Peake, I. R., Bloom, A. L., Anson, D. S.
|
|
<strong>Carrier detection through the use of abnormal deletion junction fragments in a case of haemophilia B involving complete deletion of the factor IX gene.</strong>
|
|
J. Med. Genet. 25: 779-780, 1988.
|
|
|
|
|
|
[PubMed: 2907054]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.25.11.779]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McCord, D. M., Monroe, D. M., Smith, K. J., Roberts, H. R.
|
|
<strong>Characterization of the functional defect in factor IX Alabama: evidence for a conformational change due to high affinity calcium binding in the first epidermal growth factor domain.</strong>
|
|
J. Biol. Chem. 265: 10250-10254, 1990.
|
|
|
|
|
|
[PubMed: 2355000]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McGraw, R. A., Davis, L. M., Noyes, C. M., Lundblad, R. L., Roberts, H. R., Graham, J. B., Stafford, D. W.
|
|
<strong>Evidence for a prevalent dimorphism in the activation peptide of human coagulation factor IX.</strong>
|
|
Proc. Nat. Acad. Sci. 82: 2847-2851, 1985.
|
|
|
|
|
|
[PubMed: 3857619]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.82.9.2847]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mikami, S., Nishino, M., Nishimura, T., Fukui, H.
|
|
<strong>RFLPs of factor IX gene in Japanese haemophilia B families and gene deletion in two high-responder-inhibitor patients.</strong>
|
|
Jpn. J. Hum. Genet. 32: 21-31, 1987.
|
|
|
|
|
|
[PubMed: 2886685]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01876524]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Miyata, T., Sakai, T., Sugimoto, M., Naka, H., Yamamoto, K., Yoshioka, A., Fukui, H., Mitsui, K., Kamiya, K., Umeyama, H., Iwanaga, S.
|
|
<strong>Factor IX Amagasaki: a new mutation in the catalytic domain resulting in the loss of both coagulant and esterase activities.</strong>
|
|
Biochemistry 30: 11286-11291, 1991.
|
|
|
|
|
|
[PubMed: 1958666]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1021/bi00111a014]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Montandon, A. J., Green, P. M., Bentley, D. R., Ljung, R., Nilsson, I. M., Giannelli, F.
|
|
<strong>Two factor IX mutations in the family of an isolated haemophilia B patient: direct carrier diagnosis by amplification mismatch detection (AMD).</strong>
|
|
Hum. Genet. 85: 200-204, 1990.
|
|
|
|
|
|
[PubMed: 2370049]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00193196]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Noyes, C. M., Griffith, M. J., Roberts, H. R., Lundblad, R. L.
|
|
<strong>Identification of the molecular defect in factor IX(Chapel Hill): substitution of histidine for arginine at position 145.</strong>
|
|
Proc. Nat. Acad. Sci. 80: 4200-4202, 1983.
|
|
|
|
|
|
[PubMed: 6603618]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.80.14.4200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Oldenburg, J., Kriz, K., Wuillemin, W. A., Maly, F. E., von Felten, A., Siegemund, A., Keeling, D. M., Baker, P., Chu, K., Konkle, B. A., Lammle, B., Albert, T.
|
|
<strong>Genetic predisposition to bleeding during oral anticoagulant therapy: evidence for common founder mutations (FIXVal-10 and FIXThr-10) and an independent CpG hotspot mutation (FIXThr-10).</strong>
|
|
Thromb. Haemost. 85: 454-457, 2001.
|
|
|
|
|
|
[PubMed: 11307814]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Oldenburg, J., Quenzel, E.-M., Harbrecht, U., Fregin, A., Kress, W., Muller, C. R., Hertefelder, H.-J., Schwaab, R., Brackmann, H.-H., Hanfland, P.
|
|
<strong>Missense mutations at ala-10 in the factor IX propeptide: an insignificant variant in normal life but a decisive cause of bleeding during oral anticoagulant therapy.</strong>
|
|
Brit. J. Haemat. 98: 240-244, 1997.
|
|
|
|
|
|
[PubMed: 9233593]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1365-2141.1997.2213036.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Peake, I. R., Furlong, B. L., Bloom, A. L.
|
|
<strong>Carrier detection by direct gene analysis in a family with haemophilia B (factor IX deficiency).</strong>
|
|
Lancet 323: 242-243, 1984. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: 6142993]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(84)90123-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Peake, I. R., Matthews, R. J., Bloom, A. L.
|
|
<strong>Haemophilia B Chicago: severe haemophilia B caused by two deletions and an inversion within the factor IX gene.</strong>
|
|
Brit. J. Haemat. 71 (suppl. 1): 1, 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pezeshkpoor, B., Czogalla, K. J., Caspers, M., Berkemeier, A.-C., Liphardt, K., Ghosh, S., Kellner, M., Ulrich, S., Pavlova, A., Oldenburg, J.
|
|
<strong>Variants in FIX propeptide associated with vitamin K antagonism hypersensitivity: functional analysis and additional data confirming the common founder mutations.</strong>
|
|
Ann. Hemat. 97: 1061-1069, 2018.
|
|
|
|
|
|
[PubMed: 29450643]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00277-018-3264-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Picketts, D. J., D'Souza, C., Bridge, P. J., Lillicrap, D.
|
|
<strong>An A to T transversion at position -5 of the factor IX promoter results in hemophilia B.</strong>
|
|
Genomics 12: 161-163, 1992.
|
|
|
|
|
|
[PubMed: 1733855]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(92)90421-n]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Picketts, D. J., Lillicrap, D. P., Mueller, C. R.
|
|
<strong>Synergy between transcription factors DBP and C/EBP compensates for a haemophilia B Leyden factor IX mutation.</strong>
|
|
Nature Genet. 3: 175-179, 1993.
|
|
|
|
|
|
[PubMed: 8499951]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0293-175]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Poort, S. R., Briet, E., Bertina, R. M., Reitsma, P. H.
|
|
<strong>A Dutch pedigree with mild hemophilia B with a missense mutation in the first EGF domain [factor IX(Oud en Nieuw Gastel)].</strong>
|
|
Nucleic Acids Res. 17: 5869, 1989.
|
|
|
|
|
|
[PubMed: 2762170]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/17.14.5869]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rees, D. J. G., Rizza, C. R., Brownlee, G. G.
|
|
<strong>Haemophilia B caused by a point mutation in a donor splice junction of the human factor IX gene.</strong>
|
|
Nature 316: 643-645, 1985.
|
|
|
|
|
|
[PubMed: 4033760]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/316643a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Reijnen, M. J., Sladek, F. M., Bertina, R. M., Reitsma, P. H.
|
|
<strong>Disruption of a binding site for hepatocyte nuclear factor 4 results in hemophilia B Leyden.</strong>
|
|
Proc. Nat. Acad. Sci. 89: 6300-6303, 1992.
|
|
|
|
|
|
[PubMed: 1631121]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.89.14.6300]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Reitsma, P. H., Bertina, R. M., Ploos van Amstel, J. K., Riemens, A., Briet, E.
|
|
<strong>The putative factor IX gene promoter in hemophilia B Leyden.</strong>
|
|
Blood 72: 1074, 1988.
|
|
|
|
|
|
[PubMed: 3416069]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Reitsma, P. H., Mandalaki, T., Kasper, C. K., Bertina, R. M., Briet, E.
|
|
<strong>Two novel point mutations correlate with an altered developmental expression of blood coagulation factor IX (hemophilia B Leyden phenotype).</strong>
|
|
Blood 73: 743-746, 1989.
|
|
|
|
|
|
[PubMed: 2917196]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rogaev, E. I., Grigorenko, A. P., Faskhutdinova, G., Kittler, E. L. W., Moliaka, Y. K.
|
|
<strong>Genotype analysis identifies the cause of the 'Royal disease.'</strong>
|
|
Science 326: 817 only, 2009.
|
|
|
|
|
|
[PubMed: 19815722]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1180660]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Royle, G., Van de Water, N. S., Berry, E., Ockelford, P. A., Browett, P. J.
|
|
<strong>Haemophilia B Leyden arising de novo by point mutation in the putative factor IX promoter region.</strong>
|
|
Brit. J. Haemat. 77: 191-194, 1991.
|
|
|
|
|
|
[PubMed: 2004020]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1991.tb07976.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rusconi, C. P., Scardino, E., Layzer, J., Pitoc, G. A., Ortel, T. L., Monroe, D., Sullenger, B. A.
|
|
<strong>RNA aptamers as reversible antagonists of coagulation factor IXa.</strong>
|
|
Nature 419: 90-94, 2002.
|
|
|
|
|
|
[PubMed: 12214238]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature00963]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sakai, T., Yoshioka, A., Yamamoto, K., Niinomi, K., Fujimura, Y., Fukui, H., Miyata, T., Iwanaga, S.
|
|
<strong>Blood clotting factor IX Kashihara: amino acid substitution of valine-182 by phenylalanine.</strong>
|
|
J. Biochem. 105: 756-759, 1989.
|
|
|
|
|
|
[PubMed: 2753873]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/oxfordjournals.jbchem.a122740]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sarkar, G., Cassady, J. D., Pyeritz, R. E., Gilchrist, G. S., Sommer, S. S.
|
|
<strong>Isoleucine-397 is changed to threonine in two females with hemophilia B.</strong>
|
|
Nucleic Acids Res. 19: 1165, 1991.
|
|
|
|
|
|
[PubMed: 1902289]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/19.5.1165]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schach, B. G., Yoshitake, S., Davie, E. W.
|
|
<strong>Hemophilia B (factor IX-Seattle 2) due to a single nucleotide deletion in the gene for factor IX.</strong>
|
|
J. Clin. Invest. 80: 1023-1028, 1987.
|
|
|
|
|
|
[PubMed: 2821070]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI113155]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Siguret, V., Amselem, S., Vidaud, M., Assouline, Z., Kerbiriou-Nabias, D., Pietu, G., Goossens, M., Larrieu, M. J., Bahnak, B., Meyer, D., Lavergne, J. M.
|
|
<strong>Identification of a CpG mutation in the coagulation factor-IX gene by analysis of amplified DNA sequences.</strong>
|
|
Brit. J. Haemat. 70: 411-416, 1988.
|
|
|
|
|
|
[PubMed: 3219291]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1988.tb02509.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Simioni, P., Tormene, D., Tognin, G., Gavasso, S., Bulato, C., Iacobelli, N. P., Finn, J. D., Spiezia, L., Radu, C., Arruda, V. R.
|
|
<strong>X-linked thrombophilia with a mutant factor IX (factor IX Padua).</strong>
|
|
New Eng. J. Med. 361: 1671-1675, 2009.
|
|
|
|
|
|
[PubMed: 19846852]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa0904377]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Smith, K. J.
|
|
<strong>Monoclonal antibodies to coagulation factor IX define a high-frequency polymorphism by immunoassays.</strong>
|
|
Am. J. Hum. Genet. 37: 668-679, 1985.
|
|
|
|
|
|
[PubMed: 9556657]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Solera, J., Magallon, M., Martin-Villar, J., Coloma, A.
|
|
<strong>Factor IX(Madrid 2): a deletion/insertion in factor IX gene which abolishes the sequence of the donor junction at the exon IV-intron d splice site.</strong>
|
|
Am. J. Hum. Genet. 50: 434-437, 1992.
|
|
|
|
|
|
[PubMed: 1346483]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sommer, S. S., Bowie, E. J. W., Ketterling, R. P., Bottema, C. D. K.
|
|
<strong>Missense mutations and the magnitude of functional deficit: the example of factor IX.</strong>
|
|
Hum. Genet. 89: 295-297, 1992.
|
|
|
|
|
|
[PubMed: 1601420]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00220543]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sommer, S. S.
|
|
<strong>Does cancer kill the individual and save the species? (Letter)</strong>
|
|
Hum. Mutat. 3: 166-169, 1994.
|
|
|
|
|
|
[PubMed: 8199598]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1380030214]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Spitzer, S. G., Pendurthi, U. R., Kasper, C. K., Bajaj, S. P.
|
|
<strong>Molecular defect in factor IX (Bm Lake Elsinore): substitution of ala390 by val in the catalytic domain.</strong>
|
|
J. Biol. Chem. 263: 10545-10548, 1988.
|
|
|
|
|
|
[PubMed: 3392024]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Spitzer, S. G., Warn-Cramer, B. J., Kasper, C. C., Pendurthi, U. R., Bajaj, S. P.
|
|
<strong>Mutations in the catalytic domain of factor IXa which prevent macromolecular catalysis. (Abstract)</strong>
|
|
Circulation 78 (suppl. II): 118, 1988.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Spitzer, S., Katzman, D., Kasper, C., Bajaj, S. P.
|
|
<strong>Factor IX Hollywood: substitution of 55 pro-to-ala in the first EGF domain. (Abstract)</strong>
|
|
Thromb. Haemost. 62: 203, 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Suehiro, K., Kawabata, S., Miyata, T., Takeya, H., Takamatsu, J., Ogata, K., Kamiya, T., Saito, H., Niho, Y., Iwanaga, S.
|
|
<strong>Blood clotting factor IX B(M) Nagoya: substitution of arginine 180 by tryptophan and its activation by alpha-chymotrypsin and rat mast cell chymase.</strong>
|
|
J. Biol. Chem. 264: 21257-21265, 1989.
|
|
|
|
|
|
[PubMed: 2592373]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Suehiro, K., Miyata, T., Takeya, H., Takamatsu, J., Saito, H., Murakawa, M., Okamura, T., Niho, Y., Iwanaga, S.
|
|
<strong>Blood clotting factor IX Nagoya 3: the molecular defect of zymogen activation caused by an arginine-145 to histidine substitution.</strong>
|
|
Thromb. Res. 60: 311-320, 1990.
|
|
|
|
|
|
[PubMed: 2087690]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0049-3848(90)90109-p]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sugimoto, M., Miyata, T., Kawabata, S., Yoshioka, A., Fukui, H., Iwanaga, S.
|
|
<strong>Factor IX Kawachinagano: impaired function of the Gla-domain caused by attached propeptide region due to substitution of arginine by glutamine at position -4.</strong>
|
|
Brit. J. Haemat. 72: 216-221, 1989.
|
|
|
|
|
|
[PubMed: 2757966]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1989.tb07685.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sugimoto, M., Miyata, T., Kawabata, S., Yoshioka, A., Fukui, H., Takahashi, H., Iwanaga, S.
|
|
<strong>Blood clotting factor IX Niigata: substitution of alanine-390 by valine in the catalytic domain.</strong>
|
|
J. Biochem. 104: 878-880, 1988.
|
|
|
|
|
|
[PubMed: 3243764]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/oxfordjournals.jbchem.a122575]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tanimoto, M., Kojima, T., Kamiya, T., Takamatsu, J., Ogata, K., Obata, Y., Inagaki, M., Iizuka, A., Nagao, T., Kurachi, K., Saito, H.
|
|
<strong>DNA analysis of seven patients with hemophilia B who have anti-factor IX antibodies: relationship to clinical manifestations and evidence that the abnormal gene was inherited.</strong>
|
|
J. Lab. Clin. Med. 112: 307-313, 1988.
|
|
|
|
|
|
[PubMed: 3411192]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Taylor, S. A. M., Deugau, K. V., Lillicrap, D. P.
|
|
<strong>Somatic mosaicism and female-to-female transmission in a kindred with hemophilia B (factor IX deficiency).</strong>
|
|
Proc. Nat. Acad. Sci. 88: 39-42, 1991.
|
|
|
|
|
|
[PubMed: 1986380]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.88.1.39]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Taylor, S. A. M., Duffin, J., Cameron, C., Teitel, J., Garvey, B., Lillicrap, D. P.
|
|
<strong>Characterization of the original Christmas disease mutation (cysteine 206-to-serine): from clinical recognition to molecular pathogenesis.</strong>
|
|
Thromb. Haemost. 67: 63-65, 1992.
|
|
|
|
|
|
[PubMed: 1615485]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Taylor, S. A. M., Liddell, M. B., Peake, I. R., Bloom, A. L., Lillicrap, D. P.
|
|
<strong>A mutation adjacent to the beta cleavage site of factor IX (valine 182 to leucine) results in mild haemophilia B(m).</strong>
|
|
Brit. J. Haemat. 75: 217-221, 1990.
|
|
|
|
|
|
[PubMed: 2372509]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1990.tb02652.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Taylor, S. A. M., Liddell, M. B., Peake, I. R., Lillicrap, D. P.
|
|
<strong>Mutations affecting cleavage of the activation peptide of factor IX as a cause of hemophilia B. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 45: A223, 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Taylor, S. A. M., Lillicrap, D. P., Blanchette, V., Giles, A. R., Holden, J. J. A., White, B. N.
|
|
<strong>A complete deletion of the factor IX gene and new TaqI variant in a hemophilia B kindred.</strong>
|
|
Hum. Genet. 79: 273-276, 1988.
|
|
|
|
|
|
[PubMed: 2841226]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00366250]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thompson, A. R., Chen, S.-H., Brayer, G. D.
|
|
<strong>Severe hemophilia B due to a G to T transversion changing gly 309 to val and inhibiting active protease conformation by preventing ion pair formation. (Abstract)</strong>
|
|
Blood 74: 134A, 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thompson, A. R.
|
|
<strong>Alloantibodies in hemophilia B binding to multiple factor IX epitopes.</strong>
|
|
Thromb. Res. 46: 169-174, 1987.
|
|
|
|
|
|
[PubMed: 2438804]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0049-3848(87)90217-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thompson, A. R.
|
|
<strong>Personal Communication.</strong>
|
|
Seattle, Wash. 11/1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tsang, T. C., Bentley, D. R., Mibashan, R. S., Giannelli, F.
|
|
<strong>A factor IX mutation, verified by direct genomic sequencing, causing haemophilia B by a novel mechanism.</strong>
|
|
EMBO J. 7: 3009-3015, 1988.
|
|
|
|
|
|
[PubMed: 3181127]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1988.tb03164.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Usharani, P., Warn-Cramer, B. J., Kasper, C. K., Bajaj, S. P.
|
|
<strong>Characterization of three abnormal factor IX variants (Bm Lake Elsinore, Long Beach, and Los Angeles) of hemophilia-B: evidence for defects affecting the latent catalytic site.</strong>
|
|
J. Clin. Invest. 75: 76-83, 1985.
|
|
|
|
|
|
[PubMed: 3965513]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI111700]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Veltkamp, J. J., Meilof, J., Remmelts, H. G., Van der Vlerk, D., Loeliger, E. A.
|
|
<strong>Another genetic variant of haemophilia B: haemophilia B Leyden.</strong>
|
|
Scand. J. Haemat. 7: 82-90, 1970.
|
|
|
|
|
|
[PubMed: 5450691]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1600-0609.1970.tb01873.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vidaud, D., Tartary, M., Costa, J.-M., Bahnak, B. R., Gispert-Sanchez, S., Fressinaud, E., Gazengel, C., Meyer, D., Goossens, M., Lavergne, J.-M., Vidaud, M.
|
|
<strong>Nucleotide substitutions at the -6 position in the promoter region of the factor IX gene result in different severity of hemophilia B Leyden: consequences for genetic counseling.</strong>
|
|
Hum. Genet. 91: 241-244, 1993.
|
|
|
|
|
|
[PubMed: 8478007]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00218264]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vidaud, D., Vidaud, M., Bahnak, B. R., Siguret, V., Sanchez, S. G., Laurian, Y., Meyer, D., Goossens, M., Lavergne, J. M.
|
|
<strong>Haemophilia B due to a de novo insertion of a human-specific Alu subfamily member within the coding region of the factor IX gene.</strong>
|
|
Europ. J. Hum. Genet. 1: 30-36, 1993.
|
|
|
|
|
|
[PubMed: 8069649]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000472385]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vidaud, M., Chabret, C., Gazengel, C., Grunebaum, L., Cazenave, J. P., Goossens, M.
|
|
<strong>A de novo intragenic deletion of the potential EGF domain of the factor IX gene in a family with severe hemophilia B.</strong>
|
|
Blood 68: 961-963, 1986.
|
|
|
|
|
|
[PubMed: 2875754]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vidaud, M., Vidaud, D., Siguret, V., Lavergne, J. M., Goossens, M.
|
|
<strong>Mutational insertion of an Alu sequence causes hemophilia B. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 45: A226, 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vogel, F., Motulsky, A. G.
|
|
<strong>Population genetics. In: Vogel, F.; Motulsky, A. G.: Human Genetics.</strong>
|
|
Berlin: Springer (pub.) 1986. Pp. 433-511.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wadelius, C., Blomback, M., Pettersson, U.
|
|
<strong>Molecular studies of haemophilia B in Sweden: identification of patients with total deletion of the factor IX gene and without inhibitory antibodies.</strong>
|
|
Hum. Genet. 81: 13-17, 1988.
|
|
|
|
|
|
[PubMed: 2848757]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00283721]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wall, R. L., McConnell, J., Moore, D., Macpherson, C. R., Marson, A.
|
|
<strong>Christmas disease, color-blindness and blood group Xg(a).</strong>
|
|
Am. J. Med. 43: 214-226, 1967.
|
|
|
|
|
|
[PubMed: 5298508]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0002-9343(67)90166-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, L., Zoppe, M., Hackeng, T. M., Griffin, J. H., Lee, K.-F., Verma, I. M.
|
|
<strong>A factor IX-deficient mouse model for hemophilia B gene therapy.</strong>
|
|
Proc. Nat. Acad. Sci. 94: 11563-11566, 1997.
|
|
|
|
|
|
[PubMed: 9326649]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.94.21.11563]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, N. S., Zhang, M., Thompson, A. R., Chen, S.-H.
|
|
<strong>Factor IX(Chongqing): a new mutation in the calcium-binding domain of factor IX resulting in severe hemophilia B.</strong>
|
|
Thromb. Haemost. 63: 24-26, 1990.
|
|
|
|
|
|
[PubMed: 2339358]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ware, J., Davis, L., Frazier, D., Bajaj, S. P., Stafford, D. W.
|
|
<strong>Genetic defect responsible for the dysfunctional protein: factor IX (Long Beach).</strong>
|
|
Blood 72: 820-822, 1988.
|
|
|
|
|
|
[PubMed: 3401602]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ware, J., Diuguid, D. L., Liebman, H. A., Rabiet, M.-J., Kasper, C. K., Furie, B. C., Furie, B., Stafford, D. W.
|
|
<strong>Factor IX San Dimas: substitution of glutamine for arg(-4) in the propeptide leads to incomplete gamma-carboxylation and altered phospholipid binding properties.</strong>
|
|
J. Biol. Chem. 264: 11401-11406, 1989.
|
|
|
|
|
|
[PubMed: 2738071]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wilkinson, F. H., London, F. S., Walsh, P. N.
|
|
<strong>Residues 88-109 of factor IXa are important for assembly of the factor X activating complex.</strong>
|
|
J. Biol. Chem. 277: 5725-5733, 2002.
|
|
|
|
|
|
[PubMed: 11726655]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M107027200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Winship, P. R., Brownlee, G. G.
|
|
<strong>Diagnosis of haemophilia B carriers using intragenic oligonucleotide probes. (Letter)</strong>
|
|
Lancet 328: 218-219, 1986. Note: Originally Volume 2.
|
|
|
|
|
|
[PubMed: 2873459]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(86)92513-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Winship, P. R., Dragon, A. C.
|
|
<strong>Identification of haemophilia B patients with mutations in the two calcium binding domains of factor IX: importance of a beta-OH asp64-to-asn change.</strong>
|
|
Brit. J. Haemat. 77: 102-109, 1991. Note: Erratum: Brit. J. Haemat. 77: 446 only, 1991.
|
|
|
|
|
|
[PubMed: 1998585]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1991.tb07955.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Winship, P. R., Rees, D. J. G., Alkan, M.
|
|
<strong>Detection of polymorphisms at cytosine phosphoguanidine dinucleotides and diagnosis of haemophilia B carriers.</strong>
|
|
Lancet 333: 631-634, 1989. Note: Originally Volume 1.
|
|
|
|
|
|
[PubMed: 2564457]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(89)92141-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Winship, P. R.
|
|
<strong>Characterisation of the molecular defect in haemophilia B patients using the polymerase chain reaction procedure. (Abstract)</strong>
|
|
Thromb. Haemost. 62: 465, 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Winship, P. R.
|
|
<strong>Haemophilia B caused by mutation of a potential thrombin cleavage site in factor IX.</strong>
|
|
Nucleic Acids Res. 18: 1310, 1990.
|
|
|
|
|
|
[PubMed: 2320433]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/18.5.1310]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yoshioka, A., Ohkubo, Y., Nishimura, T., Tanaka, I., Fukui, H., Ogata, K., Kamiya, T., Takahashi, H.
|
|
<strong>Heterogeneity of factor IX BM: difference in cleavage sites by factor XIa and Ca(2+) in factor IX Kashihara, factor IX Nagoya and factor IX Niigata.</strong>
|
|
Thromb. Res. 42: 595-604, 1986.
|
|
|
|
|
|
[PubMed: 3487139]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0049-3848(86)90338-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhang, M., Chen, S.-H., Thompson, A. R., Lovrien, E., Scott, C. R.
|
|
<strong>CG dinucleotides are 'hot spots' in the factor IX gene for point mutations: evidence from the study of 25 families with defined mutations causing hemophilia B. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 45: A231, 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
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|
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<span class="text-nowrap mim-text-font">
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Contributors:
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</span>
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</div>
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 09/29/2020<br>Ada Hamosh - updated : 12/29/2009<br>Cassandra L. Kniffin - updated : 11/25/2009<br>Cassandra L. Kniffin - updated : 11/10/2009<br>Cassandra L. Kniffin - updated : 10/24/2008
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Cassandra L. Kniffin : 10/9/2008
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carol : 01/07/2025<br>carol : 08/14/2023<br>carol : 09/30/2020<br>carol : 09/29/2020<br>carol : 07/24/2020<br>carol : 02/26/2018<br>alopez : 12/11/2017<br>carol : 10/09/2017<br>joanna : 08/04/2016<br>carol : 09/11/2013<br>carol : 11/12/2012<br>carol : 3/1/2012<br>carol : 2/29/2012<br>carol : 2/28/2012<br>carol : 7/6/2011<br>terry : 5/20/2011<br>carol : 4/7/2011<br>carol : 1/26/2011<br>carol : 10/12/2010<br>alopez : 1/5/2010<br>terry : 12/29/2009<br>wwang : 12/2/2009<br>terry : 12/1/2009<br>ckniffin : 11/25/2009<br>carol : 11/11/2009<br>ckniffin : 11/10/2009<br>terry : 6/5/2009<br>terry : 6/5/2009<br>terry : 6/3/2009<br>terry : 4/13/2009<br>terry : 4/9/2009<br>carol : 11/20/2008<br>terry : 11/19/2008<br>carol : 10/30/2008<br>ckniffin : 10/24/2008<br>carol : 10/21/2008<br>ckniffin : 10/15/2008
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