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Entry
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- *252800 - ALPHA-L-IDURONIDASE; IDUA
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*252800</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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</li>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#populationGenetics">Population 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 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/252800">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>
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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=ENSG00000127415;t=ENST00000514224" 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=3425" 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=252800" 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=ENSG00000127415;t=ENST00000514224" 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_000203,NM_001363576,NR_110313,XM_011513461,XM_047415648,XM_047415649,XM_047415650,XM_047415651,XM_047415652" 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_000203" 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=252800" 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=02016&isoform_id=02016_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/IDUA" 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/178413,184559,62087382,62089474,92090608,110611239,119603022,119603023,119603024,119603025,119603026,119603027,119603028,119603029,119603030,119603031,119603032,119603033,158257064,193785015,403240150,767929122,1240148469,1240148471,1391723658,2217350528,2217350530,2217350532,2217350535,2217350537,2462597015,2462597017,2462597019,2462597021,2462597023,2462597025,2462597027" 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/P35475" 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=3425" 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=ENSG00000127415;t=ENST00000514224" 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=IDUA" 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=IDUA" 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+3425" 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/IDUA" 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:3425" 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/3425" 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=chr4&hgg_gene=ENST00000514224.2&hgg_start=986997&hgg_end=1008351&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:5391" 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:5391" 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/idua" 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=252800[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=252800[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/IDUA/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000127415" 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=IDUA" 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=IDUA" 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=IDUA" 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="http://www.LOVD.nl/IDUA" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=IDUA&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/PA29638" 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:5391" 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://flybase.org/reports/FBgn0032343.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:96418" 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/IDUA#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:96418" 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/3425/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/OMIA000664/" 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=3425" 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-060526-29" 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="mimCellLines">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" 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="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</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="mimCellLinesLinksFold" 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://catalog.coriell.org/Search?q=OmimNum:252800" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</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">
|
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<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:3425" 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=IDUA&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> 26745009, 65327002, 73123008<br />
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<strong>ICD10CM:</strong> E76.01, E76.02, E76.03<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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252800
|
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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>
|
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<span class="mim-font">
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ALPHA-L-IDURONIDASE; IDUA
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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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<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">
|
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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>
|
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<h4>
|
|
<span class="mim-font">
|
|
IDURONIDASE, ALPHA-L
|
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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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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=IDUA" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">IDUA</a></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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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/4/22?start=-3&limit=10&highlight=22">4p16.3</a>
|
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr4:986997-1008351&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'})">4:986,997-1,008,351</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
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|
|
</span>
|
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</p>
|
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</div>
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<div>
|
|
<br />
|
|
</div>
|
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<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
|
|
</th>
|
|
<th>
|
|
Phenotype
|
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|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=607014,607015,607016" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
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<th>
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<li><a href="/graph/radial/252800" 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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<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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<p>Alpha-L-iduronidase (IDUA; <a href="https://enzyme.expasy.org/EC/3.2.1.76" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 3.2.1.76</a>), the enzyme deficient in MPS I (see <a href="/entry/607014">607014</a>, <a href="/entry/607015">607015</a>, and <a href="/entry/607016">607016</a>), hydrolyzes the terminal alpha-L-iduronic acid residues of the glycosaminoglycans dermatan sulfate and of heparan sulfate (<a href="#26" class="mim-tip-reference" title="Neufeld, E. F., Muenzer, J. <strong>The mucopolysaccharidoses. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic & Molecular Bases of Inherited Disease. Vol. II. (8th ed.)</strong> New York: McGraw-Hill (pub.) 2001."None>Neufeld and Muenzer, 2001</a>). It was originally defined as the 'Hurler corrective factor' (<a href="#5" class="mim-tip-reference" title="Barton, R. W., Neufeld, E. F. <strong>The Hurler corrective factor: purification and some properties.</strong> J. Biol. Chem. 246: 7773-7779, 1971.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4257494/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4257494</a>]" pmid="4257494">Barton and Neufeld, 1971</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4257494" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="#32" class="mim-tip-reference" title="Scott, H. S., Ashton, L. J., Eyre, H. J., Baker, E., Brooks, D. A., Callen, D. F., Sutherland, G. R., Morris, C. P., Hopwood, J. J. <strong>Chromosomal localization of the human alpha-L-iduronidase gene (IDUA) to 4p16.3.</strong> Am. J. Hum. Genet. 47: 802-807, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2220820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2220820</a>]" pmid="2220820">Scott et al. (1990)</a> used amino acid sequence data from purified human liver IDUA (<a href="#10" class="mim-tip-reference" title="Clements, P. R., Brooks, D. A., McCourt, P. A. G., Hopwood, J. J. <strong>Immunopurification and characterization of human alpha-L-iduronidase with the use of monoclonal antibodies.</strong> Biochem. J. 259: 199-208, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2470345/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2470345</a>] [<a href="https://doi.org/10.1042/bj2590199" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2470345">Clements et al., 1989</a>) to isolate both a genomic clone and a cDNA clone for IDUA. <a href="#31" class="mim-tip-reference" title="Scott, H. S., Anson, D. S., Orsborn, A. M., Nelson, P. V., Clements, P. R., Morris, C. P., Hopwood, J. J. <strong>Human alpha-L-iduronidase: cDNA isolation and expression.</strong> Proc. Nat. Acad. Sci. 88: 9695-9699, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1946389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1946389</a>] [<a href="https://doi.org/10.1073/pnas.88.21.9695" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1946389">Scott et al. (1991)</a> isolated and sequenced cDNA clones containing part of the human IDUA coding region and used PCR from reverse-transcribed RNA to obtain the full IDUA sequence. Analysis of the predicted 653-amino acid precursor protein showed that IDUA has a 26-amino acid signal peptide that is cleaved immediately before the amino terminus of the 74-kD polypeptide present in human liver IDUA. The protein sequence contains 6 potential N-glycosylation sites. Evidence of alternatively spliced mRNA from the IDUA gene was found in fibroblasts, liver, kidney, and placental RNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1946389+2470345+2220820" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="#34" class="mim-tip-reference" title="Scott, H. S., Guo, X.-H., Hopwood, J. J., Morris, C. P. <strong>Structure and sequence of the human alpha-L-iduronidase gene.</strong> Genomics 13: 1311-1313, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1505961/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1505961</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90053-u" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1505961">Scott et al. (1992)</a> demonstrated that the IDUA gene spans approximately 19 kb and contains 14 exons. The first 2 exons are separated by an intron of 566 bp; a large intron of approximately 13 kb follows, and the last 12 exons are clustered within 4.5 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1505961" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By in situ hybridization and Southern blot analysis of mouse-human cell hybrids, <a href="#32" class="mim-tip-reference" title="Scott, H. S., Ashton, L. J., Eyre, H. J., Baker, E., Brooks, D. A., Callen, D. F., Sutherland, G. R., Morris, C. P., Hopwood, J. J. <strong>Chromosomal localization of the human alpha-L-iduronidase gene (IDUA) to 4p16.3.</strong> Am. J. Hum. Genet. 47: 802-807, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2220820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2220820</a>]" pmid="2220820">Scott et al. (1990)</a> determined that the IDUA gene maps to 4p16.3, not to chromosome 22 as earlier reported by Schuchman et al. (<a href="#29" class="mim-tip-reference" title="Schuchman, E. H., Astrin, K. H., Aula, P., Desnick, R. J. <strong>Gene assignment for human alpha-L-iduronidase. (Abstract)</strong> Am. J. Hum. Genet. 34: 175A, 1982."None>1982</a>, <a href="#30" class="mim-tip-reference" title="Schuchman, E. H., Astrin, K. H., Aula, P., Desnick, R. J. <strong>Regional assignment of the structural gene for human alpha-L-iduronidase.</strong> Proc. Nat. Acad. Sci. 81: 1169-1173, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6422468/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6422468</a>] [<a href="https://doi.org/10.1073/pnas.81.4.1169" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6422468">1984</a>). <a href="#32" class="mim-tip-reference" title="Scott, H. S., Ashton, L. J., Eyre, H. J., Baker, E., Brooks, D. A., Callen, D. F., Sutherland, G. R., Morris, C. P., Hopwood, J. J. <strong>Chromosomal localization of the human alpha-L-iduronidase gene (IDUA) to 4p16.3.</strong> Am. J. Hum. Genet. 47: 802-807, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2220820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2220820</a>]" pmid="2220820">Scott et al. (1990)</a> confirmed the presence of human IDUA activity in human-mouse cell hybrids by using a monoclonal antibody specific to human IDUA. <a href="#38" class="mim-tip-reference" title="Scott, H. S., Nelson, P. V., MacDonald, M. E., Gusella, J. F., Hopwood, J. J., Morris, C. P. <strong>An 86-bp VNTR within IDUA is the basis of the D4S111 polymorphic locus.</strong> Genomics 14: 1118-1120, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1478658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1478658</a>] [<a href="https://doi.org/10.1016/s0888-7543(05)80145-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1478658">Scott et al. (1992)</a> found that the polymorphic locus D4S111 used in the diagnosis of Huntington disease (<a href="/entry/143100">143100</a>) is the consequence of an 86-bp variable number tandem repeat (VNTR) within the IDUA gene. The gene mapped to chromosome 22 by Schuchman et al. (<a href="#29" class="mim-tip-reference" title="Schuchman, E. H., Astrin, K. H., Aula, P., Desnick, R. J. <strong>Gene assignment for human alpha-L-iduronidase. (Abstract)</strong> Am. J. Hum. Genet. 34: 175A, 1982."None>1982</a>, <a href="#30" class="mim-tip-reference" title="Schuchman, E. H., Astrin, K. H., Aula, P., Desnick, R. J. <strong>Regional assignment of the structural gene for human alpha-L-iduronidase.</strong> Proc. Nat. Acad. Sci. 81: 1169-1173, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6422468/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6422468</a>] [<a href="https://doi.org/10.1073/pnas.81.4.1169" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6422468">1984</a>) by use of a polyclonal antibody in human-mouse cell hybrids may have been a crossreacting protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1478658+6422468+2220820" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#15" class="mim-tip-reference" title="Grosson, C. L. S., MacDonald, M. E., Duyao, M. P., Ambrose, C. M., Roffler-Tarlov, S., Gusella, J. F. <strong>Synteny conservation of the Huntington's disease gene and surrounding loci on mouse chromosome 5.</strong> Mammalian Genome 5: 424-428, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7919654/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7919654</a>] [<a href="https://doi.org/10.1007/BF00357002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7919654">Grosson et al. (1994)</a> mapped the homologous locus in the mouse, Idua, to chromosome 5 in a continuous linkage group that included the homolog of the Huntington disease gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7919654" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="#32" class="mim-tip-reference" title="Scott, H. S., Ashton, L. J., Eyre, H. J., Baker, E., Brooks, D. A., Callen, D. F., Sutherland, G. R., Morris, C. P., Hopwood, J. J. <strong>Chromosomal localization of the human alpha-L-iduronidase gene (IDUA) to 4p16.3.</strong> Am. J. Hum. Genet. 47: 802-807, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2220820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2220820</a>]" pmid="2220820">Scott et al. (1990)</a> failed to detect major deletions or gene rearrangements in the IDUA gene in any of the 40 MPS I patients studied by Southern blot analysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2220820" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#35" class="mim-tip-reference" title="Scott, H. S., Litjens, T., Hopwood, J. J., Morris, C. P. <strong>A common mutation for mucopolysaccharidosis type I associated with a severe Hurler syndrome phenotype.</strong> Hum. Mutat. 1: 103-108, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301196</a>] [<a href="https://doi.org/10.1002/humu.1380010204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301196">Scott et al. (1992)</a> reported the presence of a common mutation accounting for 31% of MPS I alleles in a study of 64 MPS I patients. Chemical cleavage and then direct PCR sequencing detected the mutation. The mutation is a single base substitution that introduces a stop codon at position 402 (W402X; <a href="#0001">252800.0001</a>) of the alpha-L-iduronidase protein and is associated with an extremely severe clinical phenotype in homozygotes. Patients who are compound heterozygotes having one allele carrying the W401X mutation have a wide range of clinical phenotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301196" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#36" class="mim-tip-reference" title="Scott, H. S., Litjens, T., Nelson, P. V., Brooks, D. A., Hopwood, J. J., Morris, C. P. <strong>Alpha-L-iduronidase mutations (Q70X and P533R) associate with a severe Hurler phenotype.</strong> Hum. Mutat. 1: 333-339, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301941</a>] [<a href="https://doi.org/10.1002/humu.1380010412" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301941">Scott et al. (1992)</a> identified 2 additional mutations, one that introduces a stop codon at position 70 (Q70X; <a href="#0002">252800.0002</a>) and the other that alters the proline at position 533 to an arginine (P533R; <a href="#0003">252800.0003</a>) in the 653 amino acid alpha-L-iduronidase protein. Allele-specific oligonucleotides were used to detect the mutations in a group of 73 MPS I patients and Q70X was found to account for 15% of all MPS I alleles and P533R for 3% of MPS I alleles. Both mutations are associated with an extremely severe clinical phenotype in homozygotes. MPS I patients heterozygous for either mutation may have a wide range of clinical phenotypes. Mutations W402X (<a href="#35" class="mim-tip-reference" title="Scott, H. S., Litjens, T., Hopwood, J. J., Morris, C. P. <strong>A common mutation for mucopolysaccharidosis type I associated with a severe Hurler syndrome phenotype.</strong> Hum. Mutat. 1: 103-108, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301196</a>] [<a href="https://doi.org/10.1002/humu.1380010204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301196">Scott et al., 1992</a>), Q70X, and P533R accounted for 53% of MPS I alleles, which together define 28% of MPS I genotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1301941+1301196" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Bunge, S., Kleijer, W. J., Steglich, C., Beck, M., Schwinger, E., Gal, A. <strong>Mucopolysaccharidosis type I: identification of 13 novel mutations of the alpha-L-iduronidase gene.</strong> Hum. Mutat. 6: 91-94, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7550242/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7550242</a>] [<a href="https://doi.org/10.1002/humu.1380060119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7550242">Bunge et al. (1995)</a> identified 13 novel and 7 previously reported mutations of the IDUA gene, covering 88% of mutant alleles and 86% of genotypes, in a total of 29 patients with MPS I of differing clinical severity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7550242" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#33" class="mim-tip-reference" title="Scott, H. S., Bunge, S., Gal, A., Clarke, L. A., Morris, C. P., Hopwood, J. J. <strong>Molecular genetics of mucopolysaccharidosis type I: diagnostic, clinical, and biological implications.</strong> Hum. Mutat. 6: 288-302, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8680403/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8680403</a>] [<a href="https://doi.org/10.1002/humu.1380060403" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8680403">Scott et al. (1995)</a> stated that 46 disease-producing mutations and 30 polymorphisms had been identified in the IDUA gene. In a mutation analysis of 85 mucopolysaccharidosis families (73 Hurler, 5 Hurler/Scheie, 7 Scheie), <a href="#6" class="mim-tip-reference" title="Beesley, C. E., Meaney, C. A., Greenland, G., Adams, V., Vellodi, A., Young, E. P., Winchester, B. G. <strong>Mutational analysis of 85 mucopolysaccharidosis type I families: frequency of known mutations, identification of 17 novel mutations and in vitro expression of missense mutations.</strong> Hum. Genet. 109: 503-511, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11735025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11735025</a>] [<a href="https://doi.org/10.1007/s004390100606" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11735025">Beesley et al. (2001)</a> identified 165 of the 170 mutant alleles. The 85 MPS I families were screened for 9 known mutations. W402X was the most frequent mutation in their population (43.3%) and Q70X was the second most frequent (15.9%). In 30 families, either one or both of the mutations were not identified, which accounted for 25.9% of the total alleles. All 14 exons of the alpha-L-iduronidase gene were then screened in those patients and 23 different sequence changes were found, 17 of which were previously unknown. The novel sequence changes included 4 deletions, 6 missense mutations, a splice site mutation, and a rare polymorphism. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11735025+8680403" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Alleles that cause the milder phenotypes, Hurler/Scheie and Scheie syndromes, are often missense mutations. <a href="#41" class="mim-tip-reference" title="Tieu, P. T., Bach, G., Matynia, A., Hwang, M., Neufeld, E. F. <strong>Four novel mutations underlying mild or intermediate forms of alpha-L-iduronidase deficiency (MPS IS and MPS IH/S).</strong> Hum. Mutat. 6: 55-59, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7550232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7550232</a>] [<a href="https://doi.org/10.1002/humu.1380060111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7550232">Tieu et al. (1995)</a> reported 4 novel mutations of the IDUA gene in 1 patient with the Scheie syndrome and in 3 patients with the Hurler/Scheie syndrome. The novel mutations, all single base changes, encoded the substitutions R492P (<a href="#0011">252800.0011</a>) (Scheie) and X654G (<a href="#0013">252800.0013</a>), P496L, and L490P (<a href="#0012">252800.0012</a>) (Hurler/Scheie). The L490P mutation was apparently homozygous, whereas each of the others was found in compound heterozygosity with a Hurler mutation. The deleterious nature of the mutations was confirmed by absence of enzyme activity upon transfection of the corresponding mutagenized cDNAs into COS-1 cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7550232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#2" class="mim-tip-reference" title="Aronovich, E. L., Pan, D., Whitley, C. B. <strong>Molecular genetic defect underlying alpha-L-iduronidase pseudodeficiency.</strong> Am. J. Hum. Genet. 58: 75-85, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8554071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8554071</a>]" pmid="8554071">Aronovich et al. (1996)</a> described the molecular defect underlying IDUA pseudodeficiency. The study was prompted by a patient who appeared to have, by biochemical study, both MPS I and MPS II. The common IDS mutation R468W (<a href="/entry/309900#0012">309900.0012</a>) was found in the proband, his mother, and his sister, confirming transmission of Hunter syndrome. Additionally, the proband, his sister, and his father were found to be heterozygous for a common IDUA mutation, W402X (<a href="#0001">252800.0001</a>). Notably, a new IDUA mutation, A300T (<a href="#0016">252800.0016</a>), was identified in the proband, his sister, and his mother, accounting for reduced IDUA activity in these individuals. The proband's sister was asymptomatic and her cells demonstrated normal glycosaminoglycan metabolism, thus demonstrating that the W402X/A300T compound heterozygous genotype is an IDUA pseudodeficiency state. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8554071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="#8" class="mim-tip-reference" title="Bunge, S., Kleijer, W. J., Steglich, C., Beck, M., Zuther, C., Morris, C. P., Schwinger, E., Hopwood, J. J., Scott, H. S., Gal, A. <strong>Mucopolysaccharidosis type I: identification of 8 novel mutations and determination of the frequency of the two common alpha-L-iduronidase mutations (W402X and Q70X) among European patients.</strong> Hum. Molec. Genet. 3: 861-866, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951228/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951228</a>] [<a href="https://doi.org/10.1093/hmg/3.6.861" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7951228">Bunge et al. (1994)</a> screened 46 European patients with mucopolysaccharidosis type I for mutations in the IDUA gene. The 2 common nonsense mutations, W402X and Q70X, were identified in 37% and 35% of mutant alleles, respectively. Considerable differences were seen in the frequency of these 2 mutations in patients from northern Europe (Norway and Finland) and other European countries (mainly the Netherlands and Germany). In Scandinavia, W402X and Q70X accounted for 17% and 62% of the MPS I alleles, respectively, whereas in other European countries W402X was about 2.5 times more frequent (48%) than Q70X (19%). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951228" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#14" class="mim-tip-reference" title="Gatti, R., DiNatale, P., Villani, G. R. D., Filocamo, M., Muller, V., Guo, X.-H., Nelson, P. V., Scott, H. S., Hopwood, J. J. <strong>Mutations among Italian mucopolysaccharidosis type I patients.</strong> J. Inherit. Metab. Dis. 20: 803-806, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9427149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9427149</a>] [<a href="https://doi.org/10.1023/a:1005323918923" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9427149">Gatti et al. (1997)</a> screened 27 Italian MPS I patients for IDUA mutations. Mutations were found in 18 patients, with 28 alleles identified. The 2 common mutations in northern Europeans (W402X and Q70X) accounted for only 11% and 13% of the alleles, respectively. The R89Q (<a href="#0015">252800.0015</a>) mutation, uncommon in Europeans, was found in 1 patient, accounting for 1 of 54 alleles (1.9%). The P533R, A327P and G51D mutations accounted for 11%, 5.6%, and 9.3% of the total alleles, respectively. The P533R mutation was relatively frequent in Sicily. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9427149" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a study of Israeli-Arab MPS I patients, <a href="#4" class="mim-tip-reference" title="Bach, G., Moskowitz, S. M., Tieu, P. T., Matynia, A., Neufeld, E. F. <strong>Molecular analysis of Hurler syndrome in Druze and Muslim Arab patients in Israel: multiple allelic mutations of the IDUA gene in a small geographic area.</strong> Am. J. Hum. Genet. 53: 330-338, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8328452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8328452</a>]" pmid="8328452">Bach et al. (1993)</a> identified 4 alleles, none of which had been found in Europeans. In all instances, the probands were homozygous and the parents heterozygous for the mutant alleles, as anticipated from the consanguinity in each family. One allele had 2 amino acid substitutions and was identified in a family from Gaza. The 3 single-substitution alleles were found in 7 families, 5 of them Druze, residing in a very small area of northern Israel, suggesting a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8328452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#42" class="mim-tip-reference" title="Yamagishi, A., Tomatsu, S., Fukuda, S., Uchiyama, A., Shimozawa, N., Suzuki, Y., Kondo, N., Sukegawa, K., Orii, T. <strong>Mucopolysaccharidosis type I: identification of common mutations that cause Hurler and Scheie syndromes in Japanese populations.</strong> Hum. Mutat. 7: 23-29, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8664897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8664897</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1996)7:1<23::AID-HUMU3>3.0.CO;2-Q" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8664897">Yamagishi et al. (1996)</a> studied mutations in the IDUA gene from 19 Japanese MPS I patients, including 2 pairs of sibs, with various clinical phenotypes (Hurler, 6 cases; Hurler/Scheie, 7 cases; Scheie, 6 cases). Two common mutations accounted for 42% of the 38 alleles in their patients: a novel 5-bp insertion (704ins5; <a href="#0014">252800.0014</a>), which had not been found other populations, accounted for 18%, and an R89Q mutation, found uncommonly in Caucasians, accounted for 24%. None of the patients carried W402X or the Q79X mutations commonly found in Caucasians. Homozygosity for the 704ins5 mutation was associated with a severe phenotype, and the R89Q mutation was associated with a mild phenotype. Compound heterozygosity for these 2 mutations produced an intermediate phenotype. Haplotype analysis using polymorphisms linked to the IDUA locus demonstrated that each mutation occurs on a different specific haplotype, suggesting that individuals with each of these common mutations derive from common founders. The data documented the molecular heterogeneity and racial differences in mutations in MPS I. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8664897" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Li, P., Wood, T., Thompson, J. N. <strong>Diversity of mutations and distribution of single nucleotide polymorphic alleles in the human alpha-L-iduronidase (IDUA) gene.</strong> Genet. Med. 4: 420-426, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12509712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12509712</a>] [<a href="https://doi.org/10.1097/00125817-200211000-00004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12509712">Li et al. (2002)</a> screened 22 unrelated MPS I patients from the United States and identified 11 different mutations in the IDUA gene, including 4 novel ones. The Q70X mutation (<a href="#0002">252800.0002</a>) was found in 30% of alleles and the W402X mutation (<a href="#0001">252800.0001</a>) was identified in 39% of alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12509712" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Lee, I. J., Hwang, S. H., Jeon, B. H., Song, S. M., Kim, J. S., Paik, K. H., Kwon, E. K., Jin, D.-K. <strong>Mutational analysis of the alpha-L-iduronidase gene in 10 unrelated Korean type I mucopolysaccharidosis patients: identification of four novel mutations. (Letter)</strong> Clin. Genet. 66: 575-576, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15521993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15521993</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2004.00374.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15521993">Lee et al. (2004)</a> performed mutation analysis of the IDUA gene in 10 unrelated Korean patients with the various clinical phenotypes of MPS I and identified 7 different mutations, 4 of which were novel. The 704ins5 mutation (<a href="#0014">252800.0014</a>) was found in 4 patients and the L346R mutation (<a href="#0020">252800.0020</a>) in 6. These 2 mutations accounted for half the mutations found in Korean MPS I patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15521993" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="#9" class="mim-tip-reference" title="Clarke, L. A., Giugliani, R., Guffon, N., Jones, S. A., Keenan, H. A., Munoz-Rojas, M. V., Okuyama, T., Viskochil, D., Whitley, C. B., Wijburg, F. R., Muenzer, J. <strong>Genotype-phenotype relationships in mucopolysaccharidosis type I (MPS I): insights from the International MPS I Registry.</strong> Clin. Genet. 96: 281-289, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31194252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31194252</a>] [<a href="https://doi.org/10.1111/cge.13583" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31194252">Clarke et al. (2019)</a> reported an analysis of genotype-phenotype associations in 538 patients with mucopolysaccharidosis type I and biallelic mutations in the IDUA gene. Patients included 380 with a severe phenotype (Hurler syndrome, <a href="/entry/607014">607014</a>) and 158 with an attenuated phenotype (Hurler-Scheie syndrome, <a href="/entry/607015">607015</a> or Scheie syndrome, <a href="/entry/607016">607016</a>). The majority of the patients were ascertained from clinics in Europe or North America, and Latin America was reported to be underrepresented. Of the 1,076 alleles, 148 individual mutations were reported. Seventy-four mutations, which represented 50% of all mutations, appeared only once. About 67.6% of patients with a severe phenotype had genotypes in which both mutations were predicted to severely disrupt IDUA function: nonsense mutations were the most common (71.4%), followed by missense (17.8%), splice site (4.9%), and frameshift (2.6%). The most common genotypes in patients with a severe phenotype were homozygosity for W402X (<a href="#0001">252800.0001</a>) (28.7%), compound heterozygosity for W402X and Q70X (<a href="#0002">252800.0002</a>) (16.1%), and homozygosity for Q70X (6.3%). Of patients with an attenuated phenotype, 96.1% had at least 1 missense mutation or 1 intronic mutation. The most common mutations among patients with an attenuated phenotype were missense (71.8%), followed by nonsense (20.6%), small deletions with no frameshift (3.2%), and splice site (2.8%); the most common genotypes were homozygosity for L490P (<a href="#0012">252800.0012</a>) (13.3%), homozygosity for P533R (<a href="#0003">252800.0003</a>) (10.8%), and compound heterozygosity for L238Q and W402X (3.8%). <a href="#9" class="mim-tip-reference" title="Clarke, L. A., Giugliani, R., Guffon, N., Jones, S. A., Keenan, H. A., Munoz-Rojas, M. V., Okuyama, T., Viskochil, D., Whitley, C. B., Wijburg, F. R., Muenzer, J. <strong>Genotype-phenotype relationships in mucopolysaccharidosis type I (MPS I): insights from the International MPS I Registry.</strong> Clin. Genet. 96: 281-289, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31194252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31194252</a>] [<a href="https://doi.org/10.1111/cge.13583" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31194252">Clarke et al. (2019)</a> also reported several mutations where, even within the same genotype, the phenotype was variable. For example, homozygosity for an A327P mutation was reported in 5 patients, 3 of whom had severe disease and 2 of whom had attenuated disease. Homozygosity for a P533R mutation was reported in 24 patients, 7 of whom had severe disease and 17 of whom had attenuated disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31194252" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#39" class="mim-tip-reference" title="Stoltzfus, L. J., Sosa-Pineda, B., Moskowitz, S. M., Menon, K. P., Dlott, B., Hooper, L., Teplow, D. B., Shull, R. M., Neufeld, E. F. <strong>Cloning and characterization of cDNA encoding canine alpha-L-iduronidase: mRNA deficiency in mucopolysaccharidosis I dog.</strong> J. Biol. Chem. 267: 6570-6575, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1551868/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1551868</a>]" pmid="1551868">Stoltzfus et al. (1992)</a> cloned and characterized cDNA encoding the canine alpha-L-iduronidase and demonstrated mRNA deficiency in the MPS I dog. <a href="#22" class="mim-tip-reference" title="Menon, K. P., Tieu, P. T., Neufeld, E. F. <strong>Architecture of the canine IDUA gene and mutation underlying canine mucopolysaccharidosis I.</strong> Genomics 14: 763-768, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1339393/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1339393</a>] [<a href="https://doi.org/10.1016/s0888-7543(05)80182-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1339393">Menon et al. (1992)</a> demonstrated that the canine IDUA gene has 14 exons spread over 13 kb. An unusual GC dinucleotide was found at the donor splice site of intron 11. A transcriptional start site was identified by primer extension 177 bp upstream of the initiator AUG codon. The upstream region was found to be similar to the promoter region of many housekeeping genes: it is GC rich and has 7 potential Sp1 binding sites but no TATA box or CAAT motif. The mutation in canine MPS I was found to be a G-to-A transition in the donor splice site in intron 1. The mutation caused retention of intron 1 in the RNA and created a premature termination codon at the exon-intron junction. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1339393+1551868" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="#35" class="mim-tip-reference" title="Scott, H. S., Litjens, T., Hopwood, J. J., Morris, C. P. <strong>A common mutation for mucopolysaccharidosis type I associated with a severe Hurler syndrome phenotype.</strong> Hum. Mutat. 1: 103-108, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301196</a>] [<a href="https://doi.org/10.1002/humu.1380010204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301196">Scott et al. (1992)</a> found that 31% of MPS I alleles in a study of 64 patients with Hurler syndrome (<a href="/entry/607014">607014</a>) had a trp402-to-ter (W402X) substitution in the alpha-L-iduronidase protein associated with very severe clinical phenotype in homozygotes. A G-to-A transition at nucleotide 1293 altered the W402 codon (TGG) to a stop codon (TAG); translation was terminated approximately two-thirds of the way through the 653-amino acid IDUA protein. The mutation was originally detected by chemical cleavage and then by direct PCR sequencing. The patients who were compound heterozygotes for the allele had a wide range of clinical phenotypes. Based on polymorphisms within the IDUA gene, <a href="#35" class="mim-tip-reference" title="Scott, H. S., Litjens, T., Hopwood, J. J., Morris, C. P. <strong>A common mutation for mucopolysaccharidosis type I associated with a severe Hurler syndrome phenotype.</strong> Hum. Mutat. 1: 103-108, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301196</a>] [<a href="https://doi.org/10.1002/humu.1380010204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301196">Scott et al. (1992)</a> determined that the W402X mutation is associated with 3 different haplotypes, implying more than one origin for the mutation or intragenic recombination. The mutation introduced a MaeI restriction endonuclease site into the gene, thus enabling simple detection of the mutation. Assessment of the efficacy of bone marrow transplantation in patients homozygous for the mutation is thus possible. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301196" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Significantly, the index case of Scheie syndrome (GM1323) reported by <a href="#21" class="mim-tip-reference" title="McKusick, V. A., Kaplan, D., Wise, D., Hanley, W. B., Suddarth, S. B., Sevick, M. E., Maumanee, A. W. <strong>The genetic mucopolysaccharidoses.</strong> Medicine 44: 445-483, 1965.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4221470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4221470</a>] [<a href="https://doi.org/10.1097/00005792-196511000-00001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4221470">McKusick et al. (1965)</a>, who had been assumed to be a homozygote for a separate allele at the IDUA locus, was found in fact to be a compound heterozygote for the W402X allele. Biochemically, following the use of 2 different IDUA monoclonal antibodies, GM1323 fibroblasts had no detectable IDUA protein. They had approximately 0.3% of IDUA activity. This IDUA activity must result from a mild mutation in the other MPS I allele present in the patient. Subsequently, with definition of the mutation in the other allele (<a href="#0004">252800.0004</a>), this proved to be the case. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4221470" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Beesley, C. E., Meaney, C. A., Greenland, G., Adams, V., Vellodi, A., Young, E. P., Winchester, B. G. <strong>Mutational analysis of 85 mucopolysaccharidosis type I families: frequency of known mutations, identification of 17 novel mutations and in vitro expression of missense mutations.</strong> Hum. Genet. 109: 503-511, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11735025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11735025</a>] [<a href="https://doi.org/10.1007/s004390100606" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11735025">Beesley et al. (2001)</a> found that W402X accounted for 45.3% of mutant alleles in their study. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11735025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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=RCV000012684 OR RCV000185562 OR RCV000185563 OR RCV000276574 OR RCV000763532 OR RCV000790700 OR RCV001526587 OR RCV003390671 OR RCV003488336" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012684, RCV000185562, RCV000185563, RCV000276574, RCV000763532, RCV000790700, RCV001526587, RCV003390671, RCV003488336" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012684...</a>
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<p>By chemical cleavage followed by direct PCR sequencing, <a href="#34" class="mim-tip-reference" title="Scott, H. S., Guo, X.-H., Hopwood, J. J., Morris, C. P. <strong>Structure and sequence of the human alpha-L-iduronidase gene.</strong> Genomics 13: 1311-1313, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1505961/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1505961</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90053-u" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1505961">Scott et al. (1992)</a> detected and characterized a nonsense mutation, a C-to-T transition at nucleotide 296, that altered a gln codon at position 70 (CAG) to a stop codon (TAG). The termination of translation occurred soon after the mature 74-kD amino terminus of the IDUA protein. Using allele-specific oligonucleotides to detect mutations in a group of 73 MPS I patients, the authors found that the Q70X mutation accounted for 15% of all MPS I alleles. The mutation was associated with an extremely severe clinical phenotype in homozygotes. Patients who were compound heterozygotes showed a wide range of clinical phenotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1505961" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Beesley, C. E., Meaney, C. A., Greenland, G., Adams, V., Vellodi, A., Young, E. P., Winchester, B. G. <strong>Mutational analysis of 85 mucopolysaccharidosis type I families: frequency of known mutations, identification of 17 novel mutations and in vitro expression of missense mutations.</strong> Hum. Genet. 109: 503-511, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11735025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11735025</a>] [<a href="https://doi.org/10.1007/s004390100606" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11735025">Beesley et al. (2001)</a> found that Q70X accounted for 15.9% of alleles in their large study. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11735025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs121965021 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121965021;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/rs121965021?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=rs121965021" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121965021" 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=RCV000012685 OR RCV000208595 OR RCV000486848 OR RCV000763533 OR RCV001267070 OR RCV004595880" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012685, RCV000208595, RCV000486848, RCV000763533, RCV001267070, RCV004595880" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012685...</a>
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<p>By chemical cleavage analysis followed by direct PCR sequencing, <a href="#36" class="mim-tip-reference" title="Scott, H. S., Litjens, T., Nelson, P. V., Brooks, D. A., Hopwood, J. J., Morris, C. P. <strong>Alpha-L-iduronidase mutations (Q70X and P533R) associate with a severe Hurler phenotype.</strong> Hum. Mutat. 1: 333-339, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301941</a>] [<a href="https://doi.org/10.1002/humu.1380010412" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301941">Scott et al. (1992)</a> detected an alteration of the proline at position 533 to an arginine in the alpha-L-iduronidase protein. Using allele-specific oligonucleotides to screen for the mutation in a group of 73 MPS I (<a href="/entry/607014">607014</a>) patients, they found that the P533R mutation accounted for 3% of alleles. Homozygotes for the P533R mutation showed an extremely severe clinical phenotype; compound heterozygotes showed a wide range of clinical phenotypes. <a href="#36" class="mim-tip-reference" title="Scott, H. S., Litjens, T., Nelson, P. V., Brooks, D. A., Hopwood, J. J., Morris, C. P. <strong>Alpha-L-iduronidase mutations (Q70X and P533R) associate with a severe Hurler phenotype.</strong> Hum. Mutat. 1: 333-339, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301941</a>] [<a href="https://doi.org/10.1002/humu.1380010412" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301941">Scott et al. (1992)</a> found that 3 mutations, W402X, Q70X, and P533R, were responsible for 53% of MPS I alleles, which together defined 28% of MPS I genotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 fluorescence-assisted mismatch analysis (FAMA) and cycle sequencing of the PCR products, <a href="#1" class="mim-tip-reference" title="Alif, N., Hess, K., Straczek, J., Sebbar, S., N'Bou, A., Nabet, P., Dousset, B. <strong>Mucopolysaccharidosis type I: characterization of a common mutation that causes Hurler syndrome in Moroccan subjects.</strong> Ann. Hum. Genet. 63: 9-16, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10738517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10738517</a>] [<a href="https://doi.org/10.1046/j.1469-1809.1999.6310009.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10738517">Alif et al. (1999)</a> screened for mutations in the IDUA gene in a group of 13 Moroccan patients with MPS I and their families, including 3 sibs and twin sibs. The P553R mutation, which is rare in Europeans, was identified in 92% of mutant alleles (24 of 26). This was said to be the highest frequency of this mutation detected in patients with Hurler syndrome. None of the patients carried the W402X (<a href="#0001">252800.0001</a>) or the Q70X (<a href="#0002">252800.0002</a>) allele, the most common MPS I mutations in Europeans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10738517" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs762411583 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs762411583;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/rs762411583?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=rs762411583" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs762411583" 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=RCV000012688 OR RCV000208601 OR RCV000669065 OR RCV003137798" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012688, RCV000208601, RCV000669065, RCV003137798" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012688...</a>
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<p>In the fibroblast strain GM01323 derived from the index case of the Scheie syndrome (<a href="/entry/607016">607016</a>) reported by <a href="#21" class="mim-tip-reference" title="McKusick, V. A., Kaplan, D., Wise, D., Hanley, W. B., Suddarth, S. B., Sevick, M. E., Maumanee, A. W. <strong>The genetic mucopolysaccharidoses.</strong> Medicine 44: 445-483, 1965.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4221470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4221470</a>] [<a href="https://doi.org/10.1097/00005792-196511000-00001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4221470">McKusick et al. (1965)</a> and in a second cell line, GM01256, <a href="#24" class="mim-tip-reference" title="Moskowitz, S. M., Tieu, P. T., Neufeld, E. F. <strong>Mutation in Scheie syndrome (MPS IS): a G-to-A transition creates new splice site in intron 5 of one IDUA allele.</strong> Hum. Mutat. 2: 141-144, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8318992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8318992</a>] [<a href="https://doi.org/10.1002/humu.1380020215" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8318992">Moskowitz et al. (1993)</a> found compound heterozygosity for the same 2 mutations: a G-to-A transition in intron 5, in position -7 from exon 6, and a W402X change (TGG to TAG) in exon 9. The latter mutation, trp402-to-ter (<a href="#0001">252800.0001</a>), had previously been identified as a common MPS I mutation in the Caucasian population, present in homozygosity in some Hurler patients and in compound heterozygosity in patients with any form of MPS I, including the Scheie patient GM01323 (<a href="#35" class="mim-tip-reference" title="Scott, H. S., Litjens, T., Hopwood, J. J., Morris, C. P. <strong>A common mutation for mucopolysaccharidosis type I associated with a severe Hurler syndrome phenotype.</strong> Hum. Mutat. 1: 103-108, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301196</a>] [<a href="https://doi.org/10.1002/humu.1380010204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301196">Scott et al., 1992</a>). <a href="#24" class="mim-tip-reference" title="Moskowitz, S. M., Tieu, P. T., Neufeld, E. F. <strong>Mutation in Scheie syndrome (MPS IS): a G-to-A transition creates new splice site in intron 5 of one IDUA allele.</strong> Hum. Mutat. 2: 141-144, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8318992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8318992</a>] [<a href="https://doi.org/10.1002/humu.1380020215" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8318992">Moskowitz et al. (1993)</a> proposed that the intron 5 mutation was responsible for the Scheie phenotype in these 2 patients. The mutation created a new acceptor splice site, causing 5 intronic nucleotides to be inserted into mRNA; this out-of-frame insertion led to an almost immediate termination codon. Additional splicing of transcripts of one or both alleles at some upstream cryptic site(s) was found. Since the normal splice site was not obliterated by the intron 5 mutation, its use would allow the synthesis of some completely normal enzyme. An analogous situation had been encountered in the HEXB gene (<a href="/entry/268800">268800</a>); mutations that create a new splice site without destroying the old one, thereby permitting expression of some functional beta-hexosaminidase, had been found in a patient with juvenile Sandhoff disease (<a href="#25" class="mim-tip-reference" title="Nakano, T., Suzuki, K. <strong>Genetic cause of a juvenile form of Sandhoff disease: abnormal splicing of beta-hexosaminidase beta-chain gene transcript due to a point mutation within intron 12.</strong> J. Biol. Chem. 264: 5155-5158, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2522450/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2522450</a>]" pmid="2522450">Nakano and Suzuki, 1989</a>) and in an individual with the asymptomatic 'hexosaminidase Paris' (<a href="#13" class="mim-tip-reference" title="Dlott, B., d'Azzo, A., Quon, D. V. K., Neufeld, E. F. <strong>Two mutations produce intron insertion in mRNA and elongated beta-subunits of human beta-hexosaminidase.</strong> J. Biol. Chem. 265: 17921-17927, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2170400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2170400</a>]" pmid="2170400">Dlott et al., 1990</a>) phenotype. Indeed, <a href="#3" class="mim-tip-reference" title="Ashton, L. J., Brooks, D. A., McCourt, P. A. G., Muller, V. J., Clements, P. R., Hopwood, J. J. <strong>Immunoquantification and enzyme kinetics of alpha-L-iduronidase in cultured fibroblasts from normal controls and mucopolysaccharidosis type I patients.</strong> Am. J. Hum. Genet. 50: 787-794, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1550122/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1550122</a>]" pmid="1550122">Ashton et al. (1992)</a> and <a href="#35" class="mim-tip-reference" title="Scott, H. S., Litjens, T., Hopwood, J. J., Morris, C. P. <strong>A common mutation for mucopolysaccharidosis type I associated with a severe Hurler syndrome phenotype.</strong> Hum. Mutat. 1: 103-108, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301196</a>] [<a href="https://doi.org/10.1002/humu.1380010204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301196">Scott et al. (1992)</a> found a low level of immunoprecipitable alpha-L-iduronidase activity with normal K(m) and with probably normal specific activity in the Scheie fibroblast cell line GM01323. Although <a href="#20" class="mim-tip-reference" title="McKusick, V. A., Howell, R. R., Hussels, I. E., Neufeld, E. F., Stevenson, R. E. <strong>Allelism, nonallelism and genetic compounds among the mucopolysaccharidoses.</strong> Lancet 299: 993-996, 1972. Note: Originally Volume I.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4112371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4112371</a>] [<a href="https://doi.org/10.1016/s0140-6736(72)91159-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4112371">McKusick et al. (1972)</a> suggested that the Scheie syndrome may represent homozygosity for a mild disease allele, based on the paradigm of hemoglobinopathies SS, CC and SC, molecular studies in lysosomal storage diseases, especially the GM2 gangliosidoses (<a href="/entry/272800">272800</a>) and Gaucher disease (<a href="/entry/230800">230800</a>), demonstrate the presence of multiple mutant alleles at each disease locus and the occurrence of compound heterozygosity as well as homozygosity in the milder phenotypes. The findings demonstrate that just one allele, if it permits residual enzyme activity, can protect from severe disease (<a href="#27" class="mim-tip-reference" title="Neufeld, E. F. <strong>Lysosomal storage diseases.</strong> Annu. Rev. Biochem. 60: 257-280, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1883197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1883197</a>] [<a href="https://doi.org/10.1146/annurev.bi.60.070191.001353" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1883197">Neufeld, 1991</a>). Scheie syndrome must be genetically heterogeneous inasmuch as 2 other patients with this phenotype did not have the intron 5 allele. One wonders what the homozygote for this IVS5AS mutation might show phenotypically; the abnormalities might be relatively mild and late in onset, if present at all. By chemical cleavage and direct PCR sequencing, <a href="#37" class="mim-tip-reference" title="Scott, H. S., Litjens, T., Nelson, P. V., Thompson, P. R., Brooks, D. A., Hopwood, J. J., Morris, C. P. <strong>Identification of mutations in the alpha-L-iduronidase gene (IDUA) that cause Hurler and Scheie syndromes.</strong> Am. J. Hum. Genet. 53: 973-986, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8213840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8213840</a>]" pmid="8213840">Scott et al. (1993)</a> also found the mutation, which they referred to as 678-7g-to-a, in association with W402X in the index case of <a href="#21" class="mim-tip-reference" title="McKusick, V. A., Kaplan, D., Wise, D., Hanley, W. B., Suddarth, S. B., Sevick, M. E., Maumanee, A. W. <strong>The genetic mucopolysaccharidoses.</strong> Medicine 44: 445-483, 1965.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4221470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4221470</a>] [<a href="https://doi.org/10.1097/00005792-196511000-00001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4221470">McKusick et al. (1965)</a>. <a href="#37" class="mim-tip-reference" title="Scott, H. S., Litjens, T., Nelson, P. V., Thompson, P. R., Brooks, D. A., Hopwood, J. J., Morris, C. P. <strong>Identification of mutations in the alpha-L-iduronidase gene (IDUA) that cause Hurler and Scheie syndromes.</strong> Am. J. Hum. Genet. 53: 973-986, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8213840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8213840</a>]" pmid="8213840">Scott et al. (1993)</a> concluded that since the W402X allele in other combinations is associated with severe disease, the splice acceptor site mutation is likely to be responsible for the mild clinical phenotype because it allows a very small amount of normal mRNA to be produced. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8213840+2170400+4221470+1550122+8318992+2522450+1301196+1883197+4112371" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs11934801 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs11934801;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/rs11934801?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=rs11934801" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs11934801" 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> rs199794428 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199794428;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/rs199794428?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=rs199794428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs199794428" 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=RCV000012686 OR RCV000078375 OR RCV000327434 OR RCV000418377 OR RCV000722002" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012686, RCV000078375, RCV000327434, RCV000418377, RCV000722002" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012686...</a>
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<p>In a patient with Hurler syndrome (<a href="/entry/607014">607014</a>) in a consanguineous Muslim Arab family in Gaza, <a href="#4" class="mim-tip-reference" title="Bach, G., Moskowitz, S. M., Tieu, P. T., Matynia, A., Neufeld, E. F. <strong>Molecular analysis of Hurler syndrome in Druze and Muslim Arab patients in Israel: multiple allelic mutations of the IDUA gene in a small geographic area.</strong> Am. J. Hum. Genet. 53: 330-338, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8328452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8328452</a>]" pmid="8328452">Bach et al. (1993)</a> observed homozygosity for an IDUA allele containing 2 amino acid substitutions: a G-to-C transversion in exon 9 converting codon 409 from GGG (gly) to CGG (arg), and an A-to-T transversion in the termination codon 654 (TGA), converting it to a cys (TGT) residue. The cDNA sequence predicted an extension of 38 amino acids before the next termination codon was reached. Both mutations were found in heterozygous form in the DNA of each parent. Expression of cDNA mutagenized at one or both positions showed that gly409-to-arg caused a reduction of less than half the alpha-L-iduronidase activity, whereas the ter-to-cys mutation reduced activity by 98% compared with expression of normal cDNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8328452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0006 HURLER SYNDROME</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> rs121965022 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121965022;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/rs121965022?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=rs121965022" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121965022" 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=RCV000012689 OR RCV001851807 OR RCV003137513" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012689, RCV001851807, RCV003137513" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012689...</a>
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<p><a href="#28" class="mim-tip-reference" title="Schaap, T., Bach, G. <strong>Incidence of mucopolysaccharidoses in Israel: is Hunter disease a 'Jewish disease'?</strong> Hum. Genet. 56: 221-223, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6821579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6821579</a>] [<a href="https://doi.org/10.1007/BF00295699" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6821579">Schaap and Bach (1980)</a> found 13 Arab patients with Hurler syndrome (<a href="/entry/607014">607014</a>) but only 1 Jewish patient in Israel where ascertainment of the disorder had been complete for 15 years. The mutation in the Jewish patient was the deletion/insertion mutation described by <a href="#23" class="mim-tip-reference" title="Moskowitz, S. M., Tieu, P. T., Neufeld, E. F. <strong>A deletion/insertion mutation in the IDUA gene in a Libyan Jewish patient with Hurler syndrome (mucopolysaccharidosis IH).</strong> Hum. Mutat. 2: 71-73, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8477267/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8477267</a>] [<a href="https://doi.org/10.1002/humu.1380020113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8477267">Moskowitz et al. (1993)</a>. The Arab patients came from 8 families, 5 of which were Druze and 3 Muslim. Unexpectedly, <a href="#4" class="mim-tip-reference" title="Bach, G., Moskowitz, S. M., Tieu, P. T., Matynia, A., Neufeld, E. F. <strong>Molecular analysis of Hurler syndrome in Druze and Muslim Arab patients in Israel: multiple allelic mutations of the IDUA gene in a small geographic area.</strong> Am. J. Hum. Genet. 53: 330-338, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8328452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8328452</a>]" pmid="8328452">Bach et al. (1993)</a> found homozygosity for 3 different mutations distributed in 7 families, 5 of them Druze: mutations in exon 2 (tyr64-to-ter), exon 7 (gln310-to-ter; <a href="#0007">252800.0007</a>), and exon 8 (thr366-to-pro; <a href="#0008">252800.0008</a>). Transfection of mutagenized cDNA into COS-1 cells showed that the missense mutation thr366-to-pro permitted the expression of only trace amounts of alpha-L-iduronidase activity. The nonsense mutations were associated with abnormalities of RNA processing. The tyr64-to-ter mutation was accompanied by a very low level of mRNA and skipping of exon 2. Utilization of a cryptic splice site was observed with the gln310-to-ter mutation. The Druze and Muslim Arab populations have been separated by religion since the inception of the Ismalia or Druze religion in Egypt in the 11th century A.D. At present the Druze live in a defined geographic area of southern Syria, southern Lebanon, and northern Israel; they maintain an isolated social structure with a high rate of consanguineous marriages. The Druze population in Israel numbers about 60,000. <a href="#4" class="mim-tip-reference" title="Bach, G., Moskowitz, S. M., Tieu, P. T., Matynia, A., Neufeld, E. F. <strong>Molecular analysis of Hurler syndrome in Druze and Muslim Arab patients in Israel: multiple allelic mutations of the IDUA gene in a small geographic area.</strong> Am. J. Hum. Genet. 53: 330-338, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8328452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8328452</a>]" pmid="8328452">Bach et al. (1993)</a> anticipated that MPS in the Druze population would be caused by 1 founder mutation which might or might not be shared with the Muslim patients residing in the surrounding area. They were surprised to find that, in fact, there were 3 different mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8477267+6821579+8328452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0007 HURLER SYNDROME</strong>
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IDUA, GLN310TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121965023 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121965023;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=rs121965023" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121965023" 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=RCV000012690" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012690" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012690</a>
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<p>For discussion of the gln310-to-ter (Q310X) mutation in the IDUA gene that was found in homozygous state in patients with Hurler syndrome (<a href="/entry/607014">607014</a>) by <a href="#4" class="mim-tip-reference" title="Bach, G., Moskowitz, S. M., Tieu, P. T., Matynia, A., Neufeld, E. F. <strong>Molecular analysis of Hurler syndrome in Druze and Muslim Arab patients in Israel: multiple allelic mutations of the IDUA gene in a small geographic area.</strong> Am. J. Hum. Genet. 53: 330-338, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8328452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8328452</a>]" pmid="8328452">Bach et al. (1993)</a>, see <a href="#0006">252800.0006</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8328452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0008 HURLER SYNDROME</strong>
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IDUA, THR366PRO
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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> rs121965024 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121965024;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/rs121965024?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=rs121965024" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121965024" 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=RCV000012691" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012691" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012691</a>
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<p>For discussion of the thr366-to-pro (T366P) mutation in the IDUA gene that was found in homozygous state in patients with Hurler syndrome (<a href="/entry/607014">607014</a>) by <a href="#4" class="mim-tip-reference" title="Bach, G., Moskowitz, S. M., Tieu, P. T., Matynia, A., Neufeld, E. F. <strong>Molecular analysis of Hurler syndrome in Druze and Muslim Arab patients in Israel: multiple allelic mutations of the IDUA gene in a small geographic area.</strong> Am. J. Hum. Genet. 53: 330-338, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8328452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8328452</a>]" pmid="8328452">Bach et al. (1993)</a>, see <a href="#0006">252800.0006</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8328452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs727503967 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs727503967;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/rs727503967?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=rs727503967" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs727503967" 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=RCV000173986 OR RCV000790661 OR RCV001248893 OR RCV002498729" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000173986, RCV000790661, RCV001248893, RCV002498729" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000173986...</a>
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<p>In a patient with a severe form of Hurler syndrome (<a href="/entry/607014">607014</a>), <a href="#37" class="mim-tip-reference" title="Scott, H. S., Litjens, T., Nelson, P. V., Thompson, P. R., Brooks, D. A., Hopwood, J. J., Morris, C. P. <strong>Identification of mutations in the alpha-L-iduronidase gene (IDUA) that cause Hurler and Scheie syndromes.</strong> Am. J. Hum. Genet. 53: 973-986, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8213840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8213840</a>]" pmid="8213840">Scott et al. (1993)</a> found that the Q70X (<a href="#0002">252800.0002</a>) mutation was combined with an allele carrying a deletion of a single G residue at cDNA base 1702, resulting in a frameshift. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8213840" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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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<strong>.0010 HURLER SYNDROME</strong>
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IDUA, ARG621TER
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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> rs121965025 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121965025;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/rs121965025?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=rs121965025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121965025" 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=RCV000012692 OR RCV000780350 OR RCV001781251 OR RCV002496329" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012692, RCV000780350, RCV001781251, RCV002496329" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012692...</a>
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<p><a href="#8" class="mim-tip-reference" title="Bunge, S., Kleijer, W. J., Steglich, C., Beck, M., Zuther, C., Morris, C. P., Schwinger, E., Hopwood, J. J., Scott, H. S., Gal, A. <strong>Mucopolysaccharidosis type I: identification of 8 novel mutations and determination of the frequency of the two common alpha-L-iduronidase mutations (W402X and Q70X) among European patients.</strong> Hum. Molec. Genet. 3: 861-866, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951228/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951228</a>] [<a href="https://doi.org/10.1093/hmg/3.6.861" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7951228">Bunge et al. (1994)</a> identified an R621X mutation due to a CGA-to-TGA transition in a patient with Hurler syndrome (<a href="/entry/607014">607014</a>). The patient was a compound heterozygote, the other allele being the common W402X mutation (<a href="#0001">252800.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951228" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0011 SCHEIE SYNDROME</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> rs121965026 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121965026;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/rs121965026?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=rs121965026" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121965026" 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=RCV000012693 OR RCV001781252 OR RCV001851808 OR RCV004795397" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012693, RCV001781252, RCV001851808, RCV004795397" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012693...</a>
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<p>In a patient with Scheie syndrome (<a href="/entry/607016">607016</a>), <a href="#41" class="mim-tip-reference" title="Tieu, P. T., Bach, G., Matynia, A., Hwang, M., Neufeld, E. F. <strong>Four novel mutations underlying mild or intermediate forms of alpha-L-iduronidase deficiency (MPS IS and MPS IH/S).</strong> Hum. Mutat. 6: 55-59, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7550232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7550232</a>] [<a href="https://doi.org/10.1002/humu.1380060111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7550232">Tieu et al. (1995)</a> found a heterozygous G-to-C transversion in codon 492, corresponding to a change of arginine (CGG) to proline (CCG). The mutation, which created an ApaI site, was inherited from the patient's mother. No alpha-L-iduronidase activity was observed when cDNA containing the R492P mutation was expressed in COS-1 cells. Even though no activity was observed, this mutation must be presumed responsible for the mild Scheie phenotype, because the other allele carried the gln70-to-ter Hurler mutation associated with severe disease (<a href="#0002">252800.0002</a>). This was the third mutation to be described in the Scheie syndrome; in each case, there was compound heterozygosity for a common Hurler mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7550232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0012 HURLER-SCHEIE SYNDROME</strong>
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IDUA, LEU490PRO
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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> rs121965027 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121965027;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/rs121965027?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=rs121965027" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121965027" 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=RCV000012694 OR RCV000173657 OR RCV000790664 OR RCV001204340" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012694, RCV000173657, RCV000790664, RCV001204340" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012694...</a>
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<p><a href="#41" class="mim-tip-reference" title="Tieu, P. T., Bach, G., Matynia, A., Hwang, M., Neufeld, E. F. <strong>Four novel mutations underlying mild or intermediate forms of alpha-L-iduronidase deficiency (MPS IS and MPS IH/S).</strong> Hum. Mutat. 6: 55-59, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7550232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7550232</a>] [<a href="https://doi.org/10.1002/humu.1380060111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7550232">Tieu et al. (1995)</a> demonstrated that the Hurler/Scheie (<a href="/entry/607015">607015</a>) cell line GM00512 had a T-to-C transition in codon 490, converting leucine (CTG) to proline (CCG), and creating a SmaI site. No alpha-L-iduronidase activity was detected when cDNA containing the L490P mutation was expressed in COS-1 cells. There was no evidence for heterozygosity either in the genomic sequence or in the restriction digest, suggesting that the mutation was present in homozygous form. However, hemizygosity, because of either deletion of the IDUA gene on 1 chromosome or uniparental disomy, had not been ruled out. The GM00512 cell line was derived from a patient of Asian Indian origin, whose parents were not known to be consanguineous. Homozygosity had been observed previously only in consanguineous families or for the most common mutations, W402X (<a href="#0001">252800.0001</a>) and Q70X (<a href="#0002">252800.0002</a>). It is therefore possible that the L490P mutation is relatively common among Indian MPS I patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7550232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="0013" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0013 HURLER-SCHEIE SYNDROME</strong>
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IDUA, TER654GLY
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121965028 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121965028;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=rs121965028" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121965028" 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">rs387906504 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906504;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=rs387906504" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906504" 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=RCV000012695 OR RCV000208602" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012695, RCV000208602" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012695...</a>
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<p>In a patient with Hurler/Scheie syndrome (<a href="/entry/607015">607015</a>), <a href="#41" class="mim-tip-reference" title="Tieu, P. T., Bach, G., Matynia, A., Hwang, M., Neufeld, E. F. <strong>Four novel mutations underlying mild or intermediate forms of alpha-L-iduronidase deficiency (MPS IS and MPS IH/S).</strong> Hum. Mutat. 6: 55-59, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7550232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7550232</a>] [<a href="https://doi.org/10.1002/humu.1380060111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7550232">Tieu et al. (1995)</a> observed a heterozygous T-to-G transversion in the IDUA gene that changed the termination codon (TGA) to glycine (GGA), which predicted an extension of 38 amino acids at the C terminus of the protein. The mutation, which created a BstNI site, was inherited from the mother. A very low level of alpha-L-iduronidase activity was observed when the mutagenized cDNA was expressed in COS-1 cells. This mutation must have been responsible for the Hurler/Scheie phenotype, as the other allele carried the Q70X Hurler mutation (<a href="#0002">252800.0002</a>). Another mutation in the termination codon, X654C, had previously been observed in cells of a patient (GM01898) whose phenotype could not be clearly classified as either Hurler or Hurler/Scheie (<a href="#4" class="mim-tip-reference" title="Bach, G., Moskowitz, S. M., Tieu, P. T., Matynia, A., Neufeld, E. F. <strong>Molecular analysis of Hurler syndrome in Druze and Muslim Arab patients in Israel: multiple allelic mutations of the IDUA gene in a small geographic area.</strong> Am. J. Hum. Genet. 53: 330-338, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8328452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8328452</a>]" pmid="8328452">Bach et al., 1993</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8328452+7550232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0014 HURLER SYNDROME</strong>
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IDUA, 5-BP INS, NT704
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs786200915 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786200915;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=rs786200915" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs786200915" 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=RCV000012696 OR RCV000208610" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012696, RCV000208610" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012696...</a>
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<p>In the study of 19 Japanese MPS I (<a href="/entry/607014">607014</a>) patients with various clinical phenotypes, <a href="#42" class="mim-tip-reference" title="Yamagishi, A., Tomatsu, S., Fukuda, S., Uchiyama, A., Shimozawa, N., Suzuki, Y., Kondo, N., Sukegawa, K., Orii, T. <strong>Mucopolysaccharidosis type I: identification of common mutations that cause Hurler and Scheie syndromes in Japanese populations.</strong> Hum. Mutat. 7: 23-29, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8664897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8664897</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1996)7:1<23::AID-HUMU3>3.0.CO;2-Q" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8664897">Yamagishi et al. (1996)</a> found that a 5-bp insertion between the T at nucleotide 704 and the C at nucleotide 705 accounted for 7 of 38 alleles (18%). This mutation had not been found in any Caucasian patients. It was associated with a specific haplotype, suggesting to the authors that the individuals with the mutation derived from a common ancestor. Homozygosity of the 704ins5 mutation was associated with a severe phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8664897" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Lee, I. J., Hwang, S. H., Jeon, B. H., Song, S. M., Kim, J. S., Paik, K. H., Kwon, E. K., Jin, D.-K. <strong>Mutational analysis of the alpha-L-iduronidase gene in 10 unrelated Korean type I mucopolysaccharidosis patients: identification of four novel mutations. (Letter)</strong> Clin. Genet. 66: 575-576, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15521993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15521993</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2004.00374.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15521993">Lee et al. (2004)</a> found the 704ins5 mutation in 4 of 10 unrelated Korean patients with MPS I. All occurred in compound heterozygous state in patients with Hurler syndrome (<a href="/entry/607014">607014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15521993" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0015 HURLER-SCHEIE SYNDROME</strong>
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HURLER SYNDROME, INCLUDED
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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> rs121965029 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121965029;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/rs121965029?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=rs121965029" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121965029" 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=RCV000012697 OR RCV000169784 OR RCV000208598 OR RCV005042034" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012697, RCV000169784, RCV000208598, RCV005042034" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012697...</a>
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<p>In the study of 19 Japanese MPS I patients with various clinical phenotypes, <a href="#42" class="mim-tip-reference" title="Yamagishi, A., Tomatsu, S., Fukuda, S., Uchiyama, A., Shimozawa, N., Suzuki, Y., Kondo, N., Sukegawa, K., Orii, T. <strong>Mucopolysaccharidosis type I: identification of common mutations that cause Hurler and Scheie syndromes in Japanese populations.</strong> Hum. Mutat. 7: 23-29, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8664897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8664897</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1996)7:1<23::AID-HUMU3>3.0.CO;2-Q" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8664897">Yamagishi et al. (1996)</a> found that the R89Q mutation accounted for 9 of 38 alleles (24%). Homozygosity for the R89Q mutation was associated with a mild phenotype. Compound heterozygosity for this and the 704ins5 mutation (<a href="#0014">252800.0014</a>) produced an intermediate phenotype (<a href="/entry/607015">607015</a>). Haplotype analysis using polymorphisms linked to the IDUA locus demonstrated that the mutation occurred on a specific haplotype, suggesting to the authors that individuals with the mutation derived from a common ancestor. Of 3 homozygotes, 1 died of congestive heart failure at the age of 48 years. One of the heterozygotes died of the same at 31 years. She was 117 cm tall. <a href="#37" class="mim-tip-reference" title="Scott, H. S., Litjens, T., Nelson, P. V., Thompson, P. R., Brooks, D. A., Hopwood, J. J., Morris, C. P. <strong>Identification of mutations in the alpha-L-iduronidase gene (IDUA) that cause Hurler and Scheie syndromes.</strong> Am. J. Hum. Genet. 53: 973-986, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8213840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8213840</a>]" pmid="8213840">Scott et al. (1993)</a> had previously described the R89Q mutation in compound heterozygous state with the W402X mutation (<a href="#0001">252800.0001</a>) in Caucasian Hurler syndrome (<a href="/entry/607014">607014</a>) patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8664897+8213840" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0016 IDUA PSEUDODEFICIENCY</strong>
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IDUA, ALA300THR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121965030 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121965030;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=rs121965030" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121965030" 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=RCV000012698 OR RCV000667026 OR RCV001206227 OR RCV003129751" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012698, RCV000667026, RCV001206227, RCV003129751" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012698...</a>
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<p>In a healthy female, <a href="#2" class="mim-tip-reference" title="Aronovich, E. L., Pan, D., Whitley, C. B. <strong>Molecular genetic defect underlying alpha-L-iduronidase pseudodeficiency.</strong> Am. J. Hum. Genet. 58: 75-85, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8554071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8554071</a>]" pmid="8554071">Aronovich et al. (1996)</a> found compound heterozygosity for the W402X mutation (<a href="#0001">252800.0001</a>) and a new IDUA mutation, A300T. Although fibroblasts from the patient demonstrated normal glycosaminoglycan metabolism, enzyme studies using artificial substrate showed very low levels of alpha-L-iduronidase activity. This was said to have been the first IDUA pseudodeficiency gene to be elucidated at the molecular level. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8554071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0017" class="mim-anchor"></a>
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<strong>.0017 HURLER-SCHEIE SYNDROME</strong>
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IDUA, ARG619GLY
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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> rs121965031 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121965031;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/rs121965031?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=rs121965031" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121965031" 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=RCV000012699 OR RCV000666715 OR RCV003591628" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012699, RCV000666715, RCV003591628" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012699...</a>
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<p>In an 18-year-old Chinese patient with an intermediate phenotype consistent with Hurler/Scheie syndrome (<a href="/entry/607015">607015</a>), <a href="#17" class="mim-tip-reference" title="Lee-Chen, G. J., Lin, S. P., Tang, Y. F., Chin, Y. W. <strong>Mucopolysaccharidosis type I: characterization of novel mutations affecting alpha-L-iduronidase activity.</strong> Clin. Genet. 56: 66-70, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10466419/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10466419</a>] [<a href="https://doi.org/10.1034/j.1399-0004.1999.560109.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10466419">Lee-Chen et al. (1999)</a> identified homozygosity for an arg619-to-gly (R619G) mutation due to a C-to-G transversion at nucleotide 1943. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10466419" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 HURLER-SCHEIE SYNDROME</strong>
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IDUA, THR364MET
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121965032 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121965032;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=rs121965032" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121965032" 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=RCV000012700 OR RCV000588505 OR RCV000984188 OR RCV003488337 OR RCV005031435" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012700, RCV000588505, RCV000984188, RCV003488337, RCV005031435" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012700...</a>
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<p><a href="#18" class="mim-tip-reference" title="Lee-Chen, G. J., Wang, T. R. <strong>Mucopolysaccharidosis type I: identification of novel mutations that cause Hurler/Scheie syndrome in Chinese families.</strong> J. Med. Genet. 34: 939-941, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9391892/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9391892</a>] [<a href="https://doi.org/10.1136/jmg.34.11.939" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9391892">Lee-Chen and Wang (1997)</a> identified homozygosity for a thr364-to-met (T364M) mutation in the IDUA gene product in a 10-year-old Chinese patient with the Hurler/Scheie syndrome (<a href="/entry/607015">607015</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9391892" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="0019" class="mim-anchor"></a>
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<strong>.0019 HURLER-SCHEIE SYNDROME</strong>
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IDUA, IVS2AS, C-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"><span class="text-primary">●</span> rs1226056948 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1226056948;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/rs1226056948?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=rs1226056948" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1226056948" 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=RCV000012701 OR RCV000666654 OR RCV001043397" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012701, RCV000666654, RCV001043397" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012701...</a>
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<p>In a Chinese patient with Hurler/Scheie syndrome (<a href="/entry/607015">607015</a>), <a href="#40" class="mim-tip-reference" title="Teng, Y. N., Wang, T. R., Hwu, W. L., Lin, S. P., Lee-Chen, G. J. <strong>Identification and characterization of -3c-g acceptor splice site mutation in human alpha-L-iduronidase associated with mucopolysaccharidosis type IH/S.</strong> Clin. Genet. 57: 131-136, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10735634/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10735634</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2000.570207.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10735634">Teng et al. (2000)</a> identified compound heterozygosity for a maternal allele with a leu346-to-arg (L346R; <a href="#0020">252800.0020</a>) mutation (T-to-G transversion in codon 346) and a paternal allele with a C-to-G transversion at position -3 of the 3-prime splice acceptor site of intron 2. In transfected COS-7 cells, L346R showed no appreciable IDUA activity, although it did not cause an apparent reduction in IDUA mRNA or protein level. The splice acceptor site mutation profoundly affected normal splicing leading to a very unstable mRNA. Expression of IDUA cDNA containing the mutated acceptor splice site showed trace amounts of enzyme activity (1.6% of normal activity). The results provided further support for the importance of cytosine at the -3 position in RNA processing. The patient reported by <a href="#40" class="mim-tip-reference" title="Teng, Y. N., Wang, T. R., Hwu, W. L., Lin, S. P., Lee-Chen, G. J. <strong>Identification and characterization of -3c-g acceptor splice site mutation in human alpha-L-iduronidase associated with mucopolysaccharidosis type IH/S.</strong> Clin. Genet. 57: 131-136, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10735634/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10735634</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2000.570207.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10735634">Teng et al. (2000)</a> was 12 years old with short stature, macrocephaly, coarse face, corneal clouding, skeletal deformities, and hepatosplenomegaly, but normal intelligence. Other mild clinical features included hearing impairment, tracheal stenosis, hypertrophic cardiomyopathy, obstructive-type sleep apnea, adenoid hyperplasia, tonsil hypertrophy, umbilical hernia, anemia, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10735634" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0020 HURLER-SCHEIE SYNDROME</strong>
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IDUA, LEU346ARG
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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> rs121965033 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121965033;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/rs121965033?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=rs121965033" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121965033" 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=RCV000012702 OR RCV000012703 OR RCV001248726 OR RCV005042035" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012702, RCV000012703, RCV001248726, RCV005042035" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012702...</a>
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<p>For discussion of the leu346-to-arg (L346R) mutation in the IDUA gene that was found in compound heterozygous state in a patient with Hurler/Scheie syndrome (<a href="/entry/607015">607015</a>) by <a href="#40" class="mim-tip-reference" title="Teng, Y. N., Wang, T. R., Hwu, W. L., Lin, S. P., Lee-Chen, G. J. <strong>Identification and characterization of -3c-g acceptor splice site mutation in human alpha-L-iduronidase associated with mucopolysaccharidosis type IH/S.</strong> Clin. Genet. 57: 131-136, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10735634/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10735634</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2000.570207.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10735634">Teng et al. (2000)</a>, see <a href="#0019">252800.0019</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10735634" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Lee, I. J., Hwang, S. H., Jeon, B. H., Song, S. M., Kim, J. S., Paik, K. H., Kwon, E. K., Jin, D.-K. <strong>Mutational analysis of the alpha-L-iduronidase gene in 10 unrelated Korean type I mucopolysaccharidosis patients: identification of four novel mutations. (Letter)</strong> Clin. Genet. 66: 575-576, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15521993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15521993</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2004.00374.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15521993">Lee et al. (2004)</a> found the L346R mutation in 6 of 10 unrelated Korean patients with MPS I, 4 with Hurler syndrome (<a href="/entry/607014">607014</a>) and 2 with Hurler/Scheie syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15521993" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="#Clements1985" class="mim-tip-reference" title="Clements, P. R., Muller, V., Hopwood, J. J. <strong>Human alpha-L-iduronidase: 2. Catalytic properties.</strong> Europ. J. Biochem. 152: 29-34, 1985.">Clements et al. (1985)</a>; <a href="#Clements1985" class="mim-tip-reference" title="Clements, P. R., Muller, V., Hopwood, J. J. <strong>Human alpha-L-iduronidase: 2. Catalytic properties.</strong> Europ. J. Biochem. 152: 29-34, 1985.">Clements et al. (1985)</a>
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
|
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<a id="Alif1999" class="mim-anchor"></a>
|
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Alif, N., Hess, K., Straczek, J., Sebbar, S., N'Bou, A., Nabet, P., Dousset, B.
|
|
<strong>Mucopolysaccharidosis type I: characterization of a common mutation that causes Hurler syndrome in Moroccan subjects.</strong>
|
|
Ann. Hum. Genet. 63: 9-16, 1999.
|
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|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10738517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10738517</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10738517" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1046/j.1469-1809.1999.6310009.x" target="_blank">Full Text</a>]
|
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</p>
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<a id="2" class="mim-anchor"></a>
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|
|
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|
|
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|
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Aronovich, E. L., Pan, D., Whitley, C. B.
|
|
<strong>Molecular genetic defect underlying alpha-L-iduronidase pseudodeficiency.</strong>
|
|
Am. J. Hum. Genet. 58: 75-85, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8554071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8554071</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8554071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</li>
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|
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|
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|
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Ashton, L. J., Brooks, D. A., McCourt, P. A. G., Muller, V. J., Clements, P. R., Hopwood, J. J.
|
|
<strong>Immunoquantification and enzyme kinetics of alpha-L-iduronidase in cultured fibroblasts from normal controls and mucopolysaccharidosis type I patients.</strong>
|
|
Am. J. Hum. Genet. 50: 787-794, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1550122/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1550122</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1550122" 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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|
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Bach, G., Moskowitz, S. M., Tieu, P. T., Matynia, A., Neufeld, E. F.
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|
<strong>Molecular analysis of Hurler syndrome in Druze and Muslim Arab patients in Israel: multiple allelic mutations of the IDUA gene in a small geographic area.</strong>
|
|
Am. J. Hum. Genet. 53: 330-338, 1993.
|
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|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8328452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8328452</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8328452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Barton, R. W., Neufeld, E. F.
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<strong>The Hurler corrective factor: purification and some properties.</strong>
|
|
J. Biol. Chem. 246: 7773-7779, 1971.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4257494/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4257494</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4257494" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Beesley, C. E., Meaney, C. A., Greenland, G., Adams, V., Vellodi, A., Young, E. P., Winchester, B. G.
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<strong>Mutational analysis of 85 mucopolysaccharidosis type I families: frequency of known mutations, identification of 17 novel mutations and in vitro expression of missense mutations.</strong>
|
|
Hum. Genet. 109: 503-511, 2001.
|
|
|
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|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11735025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11735025</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11735025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s004390100606" target="_blank">Full Text</a>]
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Bunge, S., Kleijer, W. J., Steglich, C., Beck, M., Schwinger, E., Gal, A.
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|
<strong>Mucopolysaccharidosis type I: identification of 13 novel mutations of the alpha-L-iduronidase gene.</strong>
|
|
Hum. Mutat. 6: 91-94, 1995.
|
|
|
|
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|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7550242/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7550242</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7550242" 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.1380060119" target="_blank">Full Text</a>]
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Bunge, S., Kleijer, W. J., Steglich, C., Beck, M., Zuther, C., Morris, C. P., Schwinger, E., Hopwood, J. J., Scott, H. S., Gal, A.
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<strong>Mucopolysaccharidosis type I: identification of 8 novel mutations and determination of the frequency of the two common alpha-L-iduronidase mutations (W402X and Q70X) among European patients.</strong>
|
|
Hum. Molec. Genet. 3: 861-866, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951228/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951228</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951228" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/3.6.861" target="_blank">Full Text</a>]
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Clarke, L. A., Giugliani, R., Guffon, N., Jones, S. A., Keenan, H. A., Munoz-Rojas, M. V., Okuyama, T., Viskochil, D., Whitley, C. B., Wijburg, F. R., Muenzer, J.
|
|
<strong>Genotype-phenotype relationships in mucopolysaccharidosis type I (MPS I): insights from the International MPS I Registry.</strong>
|
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Clin. Genet. 96: 281-289, 2019.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31194252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31194252</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31194252" 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/cge.13583" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Clements1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Clements, P. R., Brooks, D. A., McCourt, P. A. G., Hopwood, J. J.
|
|
<strong>Immunopurification and characterization of human alpha-L-iduronidase with the use of monoclonal antibodies.</strong>
|
|
Biochem. J. 259: 199-208, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2470345/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2470345</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2470345" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1042/bj2590199" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Clements1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Clements, P. R., Brooks, D. A., Saccone, G. T. P., Hopwood, J. J.
|
|
<strong>Human alpha-L-iduronidase: 1. Purification, monoclonal antibody production, native and subunit molecular mass.</strong>
|
|
Europ. J. Biochem. 152: 21-28, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4043081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4043081</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4043081" 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.1432-1033.1985.tb09158.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Clements1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Clements, P. R., Muller, V., Hopwood, J. J.
|
|
<strong>Human alpha-L-iduronidase: 2. Catalytic properties.</strong>
|
|
Europ. J. Biochem. 152: 29-34, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4043083/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4043083</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4043083" 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.1432-1033.1985.tb09159.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Dlott1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dlott, B., d'Azzo, A., Quon, D. V. K., Neufeld, E. F.
|
|
<strong>Two mutations produce intron insertion in mRNA and elongated beta-subunits of human beta-hexosaminidase.</strong>
|
|
J. Biol. Chem. 265: 17921-17927, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2170400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2170400</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2170400" 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="Gatti1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gatti, R., DiNatale, P., Villani, G. R. D., Filocamo, M., Muller, V., Guo, X.-H., Nelson, P. V., Scott, H. S., Hopwood, J. J.
|
|
<strong>Mutations among Italian mucopolysaccharidosis type I patients.</strong>
|
|
J. Inherit. Metab. Dis. 20: 803-806, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9427149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9427149</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9427149" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1023/a:1005323918923" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Grosson1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Grosson, C. L. S., MacDonald, M. E., Duyao, M. P., Ambrose, C. M., Roffler-Tarlov, S., Gusella, J. F.
|
|
<strong>Synteny conservation of the Huntington's disease gene and surrounding loci on mouse chromosome 5.</strong>
|
|
Mammalian Genome 5: 424-428, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7919654/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7919654</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7919654" 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/BF00357002" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Lee2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lee, I. J., Hwang, S. H., Jeon, B. H., Song, S. M., Kim, J. S., Paik, K. H., Kwon, E. K., Jin, D.-K.
|
|
<strong>Mutational analysis of the alpha-L-iduronidase gene in 10 unrelated Korean type I mucopolysaccharidosis patients: identification of four novel mutations. (Letter)</strong>
|
|
Clin. Genet. 66: 575-576, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15521993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15521993</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15521993" 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.1399-0004.2004.00374.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Lee-Chen1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lee-Chen, G. J., Lin, S. P., Tang, Y. F., Chin, Y. W.
|
|
<strong>Mucopolysaccharidosis type I: characterization of novel mutations affecting alpha-L-iduronidase activity.</strong>
|
|
Clin. Genet. 56: 66-70, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10466419/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10466419</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10466419" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1034/j.1399-0004.1999.560109.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Lee-Chen1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lee-Chen, G. J., Wang, T. R.
|
|
<strong>Mucopolysaccharidosis type I: identification of novel mutations that cause Hurler/Scheie syndrome in Chinese families.</strong>
|
|
J. Med. Genet. 34: 939-941, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9391892/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9391892</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9391892" 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.34.11.939" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Li2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Li, P., Wood, T., Thompson, J. N.
|
|
<strong>Diversity of mutations and distribution of single nucleotide polymorphic alleles in the human alpha-L-iduronidase (IDUA) gene.</strong>
|
|
Genet. Med. 4: 420-426, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12509712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12509712</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12509712" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/00125817-200211000-00004" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="McKusick1972" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McKusick, V. A., Howell, R. R., Hussels, I. E., Neufeld, E. F., Stevenson, R. E.
|
|
<strong>Allelism, nonallelism and genetic compounds among the mucopolysaccharidoses.</strong>
|
|
Lancet 299: 993-996, 1972. Note: Originally Volume I.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4112371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4112371</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4112371" 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(72)91159-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="McKusick1965" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McKusick, V. A., Kaplan, D., Wise, D., Hanley, W. B., Suddarth, S. B., Sevick, M. E., Maumanee, A. W.
|
|
<strong>The genetic mucopolysaccharidoses.</strong>
|
|
Medicine 44: 445-483, 1965.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4221470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4221470</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4221470" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/00005792-196511000-00001" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Menon1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Menon, K. P., Tieu, P. T., Neufeld, E. F.
|
|
<strong>Architecture of the canine IDUA gene and mutation underlying canine mucopolysaccharidosis I.</strong>
|
|
Genomics 14: 763-768, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1339393/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1339393</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1339393" 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/s0888-7543(05)80182-x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Moskowitz1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Moskowitz, S. M., Tieu, P. T., Neufeld, E. F.
|
|
<strong>A deletion/insertion mutation in the IDUA gene in a Libyan Jewish patient with Hurler syndrome (mucopolysaccharidosis IH).</strong>
|
|
Hum. Mutat. 2: 71-73, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8477267/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8477267</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8477267" 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.1380020113" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Moskowitz1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Moskowitz, S. M., Tieu, P. T., Neufeld, E. F.
|
|
<strong>Mutation in Scheie syndrome (MPS IS): a G-to-A transition creates new splice site in intron 5 of one IDUA allele.</strong>
|
|
Hum. Mutat. 2: 141-144, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8318992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8318992</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8318992" 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.1380020215" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Nakano1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nakano, T., Suzuki, K.
|
|
<strong>Genetic cause of a juvenile form of Sandhoff disease: abnormal splicing of beta-hexosaminidase beta-chain gene transcript due to a point mutation within intron 12.</strong>
|
|
J. Biol. Chem. 264: 5155-5158, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2522450/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2522450</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2522450" 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="26" class="mim-anchor"></a>
|
|
<a id="Neufeld2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Neufeld, E. F., Muenzer, J.
|
|
<strong>The mucopolysaccharidoses. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic & Molecular Bases of Inherited Disease. Vol. II. (8th ed.)</strong>
|
|
New York: McGraw-Hill (pub.) 2001.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Neufeld1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Neufeld, E. F.
|
|
<strong>Lysosomal storage diseases.</strong>
|
|
Annu. Rev. Biochem. 60: 257-280, 1991.
|
|
|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1883197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1883197</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1883197" 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/10.1146/annurev.bi.60.070191.001353" target="_blank">Full Text</a>]
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|
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|
|
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|
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<a id="Schaap1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schaap, T., Bach, G.
|
|
<strong>Incidence of mucopolysaccharidoses in Israel: is Hunter disease a 'Jewish disease'?</strong>
|
|
Hum. Genet. 56: 221-223, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6821579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6821579</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6821579" 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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[<a href="https://doi.org/10.1007/BF00295699" target="_blank">Full Text</a>]
|
|
|
|
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|
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|
|
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|
|
|
|
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|
|
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|
|
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|
|
<div class="">
|
|
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|
|
Schuchman, E. H., Astrin, K. H., Aula, P., Desnick, R. J.
|
|
<strong>Gene assignment for human alpha-L-iduronidase. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 34: 175A, 1982.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
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|
|
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|
|
|
|
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|
|
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|
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<a id="Schuchman1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schuchman, E. H., Astrin, K. H., Aula, P., Desnick, R. J.
|
|
<strong>Regional assignment of the structural gene for human alpha-L-iduronidase.</strong>
|
|
Proc. Nat. Acad. Sci. 81: 1169-1173, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6422468/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6422468</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6422468" 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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[<a href="https://doi.org/10.1073/pnas.81.4.1169" target="_blank">Full Text</a>]
|
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|
|
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|
|
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|
|
|
|
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|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Scott1991" class="mim-anchor"></a>
|
|
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|
|
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|
|
Scott, H. S., Anson, D. S., Orsborn, A. M., Nelson, P. V., Clements, P. R., Morris, C. P., Hopwood, J. J.
|
|
<strong>Human alpha-L-iduronidase: cDNA isolation and expression.</strong>
|
|
Proc. Nat. Acad. Sci. 88: 9695-9699, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1946389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1946389</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1946389" 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.88.21.9695" target="_blank">Full Text</a>]
|
|
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|
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|
|
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|
|
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|
|
|
|
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|
|
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|
|
<a id="Scott1990" class="mim-anchor"></a>
|
|
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|
|
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|
|
Scott, H. S., Ashton, L. J., Eyre, H. J., Baker, E., Brooks, D. A., Callen, D. F., Sutherland, G. R., Morris, C. P., Hopwood, J. J.
|
|
<strong>Chromosomal localization of the human alpha-L-iduronidase gene (IDUA) to 4p16.3.</strong>
|
|
Am. J. Hum. Genet. 47: 802-807, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2220820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2220820</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2220820" 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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|
|
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|
|
|
|
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|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Scott1995" class="mim-anchor"></a>
|
|
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|
|
<p class="mim-text-font">
|
|
Scott, H. S., Bunge, S., Gal, A., Clarke, L. A., Morris, C. P., Hopwood, J. J.
|
|
<strong>Molecular genetics of mucopolysaccharidosis type I: diagnostic, clinical, and biological implications.</strong>
|
|
Hum. Mutat. 6: 288-302, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8680403/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8680403</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8680403" 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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[<a href="https://doi.org/10.1002/humu.1380060403" target="_blank">Full Text</a>]
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|
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|
|
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|
|
|
|
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|
|
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|
|
<a id="Scott1992" class="mim-anchor"></a>
|
|
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|
|
<p class="mim-text-font">
|
|
Scott, H. S., Guo, X.-H., Hopwood, J. J., Morris, C. P.
|
|
<strong>Structure and sequence of the human alpha-L-iduronidase gene.</strong>
|
|
Genomics 13: 1311-1313, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1505961/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1505961</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1505961" 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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[<a href="https://doi.org/10.1016/0888-7543(92)90053-u" target="_blank">Full Text</a>]
|
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|
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|
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|
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|
|
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|
|
|
|
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|
|
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|
|
<a id="Scott1992" class="mim-anchor"></a>
|
|
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|
|
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|
|
Scott, H. S., Litjens, T., Hopwood, J. J., Morris, C. P.
|
|
<strong>A common mutation for mucopolysaccharidosis type I associated with a severe Hurler syndrome phenotype.</strong>
|
|
Hum. Mutat. 1: 103-108, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301196</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301196" 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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[<a href="https://doi.org/10.1002/humu.1380010204" target="_blank">Full Text</a>]
|
|
|
|
|
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|
|
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|
|
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|
|
|
|
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|
|
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|
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|
|
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|
|
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|
|
Scott, H. S., Litjens, T., Nelson, P. V., Brooks, D. A., Hopwood, J. J., Morris, C. P.
|
|
<strong>Alpha-L-iduronidase mutations (Q70X and P533R) associate with a severe Hurler phenotype.</strong>
|
|
Hum. Mutat. 1: 333-339, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301941</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301941" 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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[<a href="https://doi.org/10.1002/humu.1380010412" target="_blank">Full Text</a>]
|
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|
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|
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|
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|
|
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|
|
|
|
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|
|
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|
|
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|
|
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|
|
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|
|
Scott, H. S., Litjens, T., Nelson, P. V., Thompson, P. R., Brooks, D. A., Hopwood, J. J., Morris, C. P.
|
|
<strong>Identification of mutations in the alpha-L-iduronidase gene (IDUA) that cause Hurler and Scheie syndromes.</strong>
|
|
Am. J. Hum. Genet. 53: 973-986, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8213840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8213840</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8213840" 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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|
|
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|
|
|
|
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|
|
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|
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|
|
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|
|
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|
|
Scott, H. S., Nelson, P. V., MacDonald, M. E., Gusella, J. F., Hopwood, J. J., Morris, C. P.
|
|
<strong>An 86-bp VNTR within IDUA is the basis of the D4S111 polymorphic locus.</strong>
|
|
Genomics 14: 1118-1120, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1478658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1478658</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1478658" 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/s0888-7543(05)80145-4" target="_blank">Full Text</a>]
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|
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|
|
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|
|
|
|
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|
|
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|
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|
|
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|
|
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|
|
Stoltzfus, L. J., Sosa-Pineda, B., Moskowitz, S. M., Menon, K. P., Dlott, B., Hooper, L., Teplow, D. B., Shull, R. M., Neufeld, E. F.
|
|
<strong>Cloning and characterization of cDNA encoding canine alpha-L-iduronidase: mRNA deficiency in mucopolysaccharidosis I dog.</strong>
|
|
J. Biol. Chem. 267: 6570-6575, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1551868/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1551868</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1551868" 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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|
|
|
|
<li>
|
|
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|
|
<a id="Teng2000" class="mim-anchor"></a>
|
|
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|
|
<p class="mim-text-font">
|
|
Teng, Y. N., Wang, T. R., Hwu, W. L., Lin, S. P., Lee-Chen, G. J.
|
|
<strong>Identification and characterization of -3c-g acceptor splice site mutation in human alpha-L-iduronidase associated with mucopolysaccharidosis type IH/S.</strong>
|
|
Clin. Genet. 57: 131-136, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10735634/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10735634</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10735634" 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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[<a href="https://doi.org/10.1034/j.1399-0004.2000.570207.x" target="_blank">Full Text</a>]
|
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|
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|
|
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|
|
|
|
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|
|
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|
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|
|
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|
|
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|
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Tieu, P. T., Bach, G., Matynia, A., Hwang, M., Neufeld, E. F.
|
|
<strong>Four novel mutations underlying mild or intermediate forms of alpha-L-iduronidase deficiency (MPS IS and MPS IH/S).</strong>
|
|
Hum. Mutat. 6: 55-59, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7550232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7550232</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7550232" 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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[<a href="https://doi.org/10.1002/humu.1380060111" target="_blank">Full Text</a>]
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|
|
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|
|
|
|
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|
|
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|
|
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|
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|
|
Yamagishi, A., Tomatsu, S., Fukuda, S., Uchiyama, A., Shimozawa, N., Suzuki, Y., Kondo, N., Sukegawa, K., Orii, T.
|
|
<strong>Mucopolysaccharidosis type I: identification of common mutations that cause Hurler and Scheie syndromes in Japanese populations.</strong>
|
|
Hum. Mutat. 7: 23-29, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8664897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8664897</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8664897" 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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[<a href="https://doi.org/10.1002/(SICI)1098-1004(1996)7:1<23::AID-HUMU3>3.0.CO;2-Q" target="_blank">Full Text</a>]
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|
|
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<br />
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 09/08/2020
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</span>
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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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Victor A. McKusick - updated : 3/31/2005<br>Victor A. McKusick - updated : 2/9/2004<br>Victor A. McKusick - updated : 11/18/2003<br>Kelly A. Przylepa - reorganized : 10/13/2003<br>Kelly A. Przylepa - updated : 10/13/2003<br>Victor A. McKusick - updated : 12/6/2001<br>George E. Tiller - updated : 4/19/2001<br>Victor A. McKusick - updated : 2/1/2001<br>Victor A. McKusick - updated : 4/21/2000<br>Sonja A. Rasmussen - updated : 3/2/2000<br>Victor A. McKusick - updated : 11/1/1999<br>Victor A. McKusick - updated : 9/8/1999<br>Victor A. McKusick - updated : 8/23/1999<br>Victor A. McKusick - updated : 3/12/1999<br>Victor A. McKusick - updated : 6/12/1998<br>Victor A. McKusick - updated : 2/19/1998<br>Victor A. McKusick - updated : 5/16/1997
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</span>
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Creation Date:
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<span class="mim-text-font">
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Victor A. McKusick : 6/4/1986
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</span>
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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carol : 09/09/2020
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carol : 09/08/2020<br>alopez : 09/16/2016<br>carol : 07/09/2016<br>carol : 6/23/2016<br>carol : 4/14/2015<br>mcolton : 4/9/2015<br>joanna : 4/6/2015<br>alopez : 10/4/2012<br>alopez : 10/4/2012<br>alopez : 10/4/2012<br>terry : 3/5/2009<br>terry : 8/26/2008<br>carol : 11/23/2005<br>carol : 11/23/2005<br>carol : 4/5/2005<br>carol : 4/5/2005<br>wwang : 4/1/2005<br>terry : 3/31/2005<br>ckniffin : 8/4/2004<br>tkritzer : 2/18/2004<br>terry : 2/9/2004<br>cwells : 11/18/2003<br>tkritzer : 11/3/2003<br>carol : 10/17/2003<br>carol : 10/13/2003<br>carol : 10/13/2003<br>carol : 10/8/2003<br>carol : 10/6/2003<br>carol : 1/2/2002<br>mcapotos : 12/13/2001<br>terry : 12/6/2001<br>cwells : 5/1/2001<br>cwells : 4/19/2001<br>mcapotos : 2/12/2001<br>mcapotos : 2/7/2001<br>mcapotos : 2/6/2001<br>terry : 2/1/2001<br>mcapotos : 5/19/2000<br>mcapotos : 5/17/2000<br>terry : 4/21/2000<br>mcapotos : 3/3/2000<br>mcapotos : 3/2/2000<br>alopez : 11/18/1999<br>carol : 11/10/1999<br>terry : 11/1/1999<br>jlewis : 9/13/1999<br>jlewis : 9/8/1999<br>jlewis : 9/8/1999<br>terry : 8/30/1999<br>terry : 8/23/1999<br>carol : 6/11/1999<br>carol : 3/16/1999<br>terry : 3/12/1999<br>dholmes : 7/9/1998<br>terry : 6/15/1998<br>terry : 6/12/1998<br>mark : 2/25/1998<br>terry : 2/19/1998<br>mark : 5/16/1997<br>terry : 5/12/1997<br>mark : 5/15/1996<br>terry : 5/10/1996<br>mark : 4/9/1996<br>terry : 4/4/1996<br>mimman : 2/8/1996<br>mark : 1/25/1996<br>mark : 1/24/1996<br>terry : 1/23/1996<br>mark : 8/3/1995<br>carol : 1/13/1995<br>terry : 8/26/1994<br>jason : 7/25/1994<br>davew : 7/6/1994<br>mimadm : 4/14/1994
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<strong>*</strong> 252800
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<h3>
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<span class="mim-font">
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ALPHA-L-IDURONIDASE; IDUA
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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IDURONIDASE, ALPHA-L
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: IDUA</em></strong>
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<strong>SNOMEDCT:</strong> 26745009, 65327002, 73123008;
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<strong>ICD10CM:</strong> E76.01, E76.02, E76.03;
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<strong>
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Cytogenetic location: 4p16.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 4:986,997-1,008,351 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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<strong>Gene-Phenotype Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<span class="mim-font">
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4p16.3
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Mucopolysaccharidosis Ih
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607014
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Autosomal recessive
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<span class="mim-font">
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3
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Mucopolysaccharidosis Ih/s
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607015
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<span class="mim-font">
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Autosomal recessive
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<span class="mim-font">
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3
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Mucopolysaccharidosis Is
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<span class="mim-font">
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607016
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<span class="mim-font">
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Autosomal recessive
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<span class="mim-font">
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3
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<strong>TEXT</strong>
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<strong>Description</strong>
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<span class="mim-text-font">
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<p>Alpha-L-iduronidase (IDUA; EC 3.2.1.76), the enzyme deficient in MPS I (see 607014, 607015, and 607016), hydrolyzes the terminal alpha-L-iduronic acid residues of the glycosaminoglycans dermatan sulfate and of heparan sulfate (Neufeld and Muenzer, 2001). It was originally defined as the 'Hurler corrective factor' (Barton and Neufeld, 1971). </p>
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<h4>
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<strong>Cloning and Expression</strong>
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<p>Scott et al. (1990) used amino acid sequence data from purified human liver IDUA (Clements et al., 1989) to isolate both a genomic clone and a cDNA clone for IDUA. Scott et al. (1991) isolated and sequenced cDNA clones containing part of the human IDUA coding region and used PCR from reverse-transcribed RNA to obtain the full IDUA sequence. Analysis of the predicted 653-amino acid precursor protein showed that IDUA has a 26-amino acid signal peptide that is cleaved immediately before the amino terminus of the 74-kD polypeptide present in human liver IDUA. The protein sequence contains 6 potential N-glycosylation sites. Evidence of alternatively spliced mRNA from the IDUA gene was found in fibroblasts, liver, kidney, and placental RNA. </p>
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<strong>Gene Structure</strong>
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<p>Scott et al. (1992) demonstrated that the IDUA gene spans approximately 19 kb and contains 14 exons. The first 2 exons are separated by an intron of 566 bp; a large intron of approximately 13 kb follows, and the last 12 exons are clustered within 4.5 kb. </p>
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<h4>
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<strong>Mapping</strong>
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</h4>
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<span class="mim-text-font">
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<p>By in situ hybridization and Southern blot analysis of mouse-human cell hybrids, Scott et al. (1990) determined that the IDUA gene maps to 4p16.3, not to chromosome 22 as earlier reported by Schuchman et al. (1982, 1984). Scott et al. (1990) confirmed the presence of human IDUA activity in human-mouse cell hybrids by using a monoclonal antibody specific to human IDUA. Scott et al. (1992) found that the polymorphic locus D4S111 used in the diagnosis of Huntington disease (143100) is the consequence of an 86-bp variable number tandem repeat (VNTR) within the IDUA gene. The gene mapped to chromosome 22 by Schuchman et al. (1982, 1984) by use of a polyclonal antibody in human-mouse cell hybrids may have been a crossreacting protein. </p><p>Grosson et al. (1994) mapped the homologous locus in the mouse, Idua, to chromosome 5 in a continuous linkage group that included the homolog of the Huntington disease gene. </p>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<span class="mim-text-font">
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<p>Scott et al. (1990) failed to detect major deletions or gene rearrangements in the IDUA gene in any of the 40 MPS I patients studied by Southern blot analysis. </p><p>Scott et al. (1992) reported the presence of a common mutation accounting for 31% of MPS I alleles in a study of 64 MPS I patients. Chemical cleavage and then direct PCR sequencing detected the mutation. The mutation is a single base substitution that introduces a stop codon at position 402 (W402X; 252800.0001) of the alpha-L-iduronidase protein and is associated with an extremely severe clinical phenotype in homozygotes. Patients who are compound heterozygotes having one allele carrying the W401X mutation have a wide range of clinical phenotypes. </p><p>Scott et al. (1992) identified 2 additional mutations, one that introduces a stop codon at position 70 (Q70X; 252800.0002) and the other that alters the proline at position 533 to an arginine (P533R; 252800.0003) in the 653 amino acid alpha-L-iduronidase protein. Allele-specific oligonucleotides were used to detect the mutations in a group of 73 MPS I patients and Q70X was found to account for 15% of all MPS I alleles and P533R for 3% of MPS I alleles. Both mutations are associated with an extremely severe clinical phenotype in homozygotes. MPS I patients heterozygous for either mutation may have a wide range of clinical phenotypes. Mutations W402X (Scott et al., 1992), Q70X, and P533R accounted for 53% of MPS I alleles, which together define 28% of MPS I genotypes. </p><p>Bunge et al. (1995) identified 13 novel and 7 previously reported mutations of the IDUA gene, covering 88% of mutant alleles and 86% of genotypes, in a total of 29 patients with MPS I of differing clinical severity. </p><p>Scott et al. (1995) stated that 46 disease-producing mutations and 30 polymorphisms had been identified in the IDUA gene. In a mutation analysis of 85 mucopolysaccharidosis families (73 Hurler, 5 Hurler/Scheie, 7 Scheie), Beesley et al. (2001) identified 165 of the 170 mutant alleles. The 85 MPS I families were screened for 9 known mutations. W402X was the most frequent mutation in their population (43.3%) and Q70X was the second most frequent (15.9%). In 30 families, either one or both of the mutations were not identified, which accounted for 25.9% of the total alleles. All 14 exons of the alpha-L-iduronidase gene were then screened in those patients and 23 different sequence changes were found, 17 of which were previously unknown. The novel sequence changes included 4 deletions, 6 missense mutations, a splice site mutation, and a rare polymorphism. </p><p>Alleles that cause the milder phenotypes, Hurler/Scheie and Scheie syndromes, are often missense mutations. Tieu et al. (1995) reported 4 novel mutations of the IDUA gene in 1 patient with the Scheie syndrome and in 3 patients with the Hurler/Scheie syndrome. The novel mutations, all single base changes, encoded the substitutions R492P (252800.0011) (Scheie) and X654G (252800.0013), P496L, and L490P (252800.0012) (Hurler/Scheie). The L490P mutation was apparently homozygous, whereas each of the others was found in compound heterozygosity with a Hurler mutation. The deleterious nature of the mutations was confirmed by absence of enzyme activity upon transfection of the corresponding mutagenized cDNAs into COS-1 cells. </p><p>Aronovich et al. (1996) described the molecular defect underlying IDUA pseudodeficiency. The study was prompted by a patient who appeared to have, by biochemical study, both MPS I and MPS II. The common IDS mutation R468W (309900.0012) was found in the proband, his mother, and his sister, confirming transmission of Hunter syndrome. Additionally, the proband, his sister, and his father were found to be heterozygous for a common IDUA mutation, W402X (252800.0001). Notably, a new IDUA mutation, A300T (252800.0016), was identified in the proband, his sister, and his mother, accounting for reduced IDUA activity in these individuals. The proband's sister was asymptomatic and her cells demonstrated normal glycosaminoglycan metabolism, thus demonstrating that the W402X/A300T compound heterozygous genotype is an IDUA pseudodeficiency state. </p>
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<h4>
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<span class="mim-font">
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<strong>Population Genetics</strong>
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</h4>
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<span class="mim-text-font">
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<p>Bunge et al. (1994) screened 46 European patients with mucopolysaccharidosis type I for mutations in the IDUA gene. The 2 common nonsense mutations, W402X and Q70X, were identified in 37% and 35% of mutant alleles, respectively. Considerable differences were seen in the frequency of these 2 mutations in patients from northern Europe (Norway and Finland) and other European countries (mainly the Netherlands and Germany). In Scandinavia, W402X and Q70X accounted for 17% and 62% of the MPS I alleles, respectively, whereas in other European countries W402X was about 2.5 times more frequent (48%) than Q70X (19%). </p><p>Gatti et al. (1997) screened 27 Italian MPS I patients for IDUA mutations. Mutations were found in 18 patients, with 28 alleles identified. The 2 common mutations in northern Europeans (W402X and Q70X) accounted for only 11% and 13% of the alleles, respectively. The R89Q (252800.0015) mutation, uncommon in Europeans, was found in 1 patient, accounting for 1 of 54 alleles (1.9%). The P533R, A327P and G51D mutations accounted for 11%, 5.6%, and 9.3% of the total alleles, respectively. The P533R mutation was relatively frequent in Sicily. </p><p>In a study of Israeli-Arab MPS I patients, Bach et al. (1993) identified 4 alleles, none of which had been found in Europeans. In all instances, the probands were homozygous and the parents heterozygous for the mutant alleles, as anticipated from the consanguinity in each family. One allele had 2 amino acid substitutions and was identified in a family from Gaza. The 3 single-substitution alleles were found in 7 families, 5 of them Druze, residing in a very small area of northern Israel, suggesting a founder effect. </p><p>Yamagishi et al. (1996) studied mutations in the IDUA gene from 19 Japanese MPS I patients, including 2 pairs of sibs, with various clinical phenotypes (Hurler, 6 cases; Hurler/Scheie, 7 cases; Scheie, 6 cases). Two common mutations accounted for 42% of the 38 alleles in their patients: a novel 5-bp insertion (704ins5; 252800.0014), which had not been found other populations, accounted for 18%, and an R89Q mutation, found uncommonly in Caucasians, accounted for 24%. None of the patients carried W402X or the Q79X mutations commonly found in Caucasians. Homozygosity for the 704ins5 mutation was associated with a severe phenotype, and the R89Q mutation was associated with a mild phenotype. Compound heterozygosity for these 2 mutations produced an intermediate phenotype. Haplotype analysis using polymorphisms linked to the IDUA locus demonstrated that each mutation occurs on a different specific haplotype, suggesting that individuals with each of these common mutations derive from common founders. The data documented the molecular heterogeneity and racial differences in mutations in MPS I. </p><p>Li et al. (2002) screened 22 unrelated MPS I patients from the United States and identified 11 different mutations in the IDUA gene, including 4 novel ones. The Q70X mutation (252800.0002) was found in 30% of alleles and the W402X mutation (252800.0001) was identified in 39% of alleles. </p><p>Lee et al. (2004) performed mutation analysis of the IDUA gene in 10 unrelated Korean patients with the various clinical phenotypes of MPS I and identified 7 different mutations, 4 of which were novel. The 704ins5 mutation (252800.0014) was found in 4 patients and the L346R mutation (252800.0020) in 6. These 2 mutations accounted for half the mutations found in Korean MPS I patients. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Genotype/Phenotype Correlations</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Clarke et al. (2019) reported an analysis of genotype-phenotype associations in 538 patients with mucopolysaccharidosis type I and biallelic mutations in the IDUA gene. Patients included 380 with a severe phenotype (Hurler syndrome, 607014) and 158 with an attenuated phenotype (Hurler-Scheie syndrome, 607015 or Scheie syndrome, 607016). The majority of the patients were ascertained from clinics in Europe or North America, and Latin America was reported to be underrepresented. Of the 1,076 alleles, 148 individual mutations were reported. Seventy-four mutations, which represented 50% of all mutations, appeared only once. About 67.6% of patients with a severe phenotype had genotypes in which both mutations were predicted to severely disrupt IDUA function: nonsense mutations were the most common (71.4%), followed by missense (17.8%), splice site (4.9%), and frameshift (2.6%). The most common genotypes in patients with a severe phenotype were homozygosity for W402X (252800.0001) (28.7%), compound heterozygosity for W402X and Q70X (252800.0002) (16.1%), and homozygosity for Q70X (6.3%). Of patients with an attenuated phenotype, 96.1% had at least 1 missense mutation or 1 intronic mutation. The most common mutations among patients with an attenuated phenotype were missense (71.8%), followed by nonsense (20.6%), small deletions with no frameshift (3.2%), and splice site (2.8%); the most common genotypes were homozygosity for L490P (252800.0012) (13.3%), homozygosity for P533R (252800.0003) (10.8%), and compound heterozygosity for L238Q and W402X (3.8%). Clarke et al. (2019) also reported several mutations where, even within the same genotype, the phenotype was variable. For example, homozygosity for an A327P mutation was reported in 5 patients, 3 of whom had severe disease and 2 of whom had attenuated disease. Homozygosity for a P533R mutation was reported in 24 patients, 7 of whom had severe disease and 17 of whom had attenuated disease. </p>
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</span>
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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>Stoltzfus et al. (1992) cloned and characterized cDNA encoding the canine alpha-L-iduronidase and demonstrated mRNA deficiency in the MPS I dog. Menon et al. (1992) demonstrated that the canine IDUA gene has 14 exons spread over 13 kb. An unusual GC dinucleotide was found at the donor splice site of intron 11. A transcriptional start site was identified by primer extension 177 bp upstream of the initiator AUG codon. The upstream region was found to be similar to the promoter region of many housekeeping genes: it is GC rich and has 7 potential Sp1 binding sites but no TATA box or CAAT motif. The mutation in canine MPS I was found to be a G-to-A transition in the donor splice site in intron 1. The mutation caused retention of intron 1 in the RNA and created a premature termination codon at the exon-intron junction. </p>
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</span>
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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>20 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 HURLER SYNDROME</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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IDUA, TRP402TER
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<br />
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SNP: rs121965019,
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gnomAD: rs121965019,
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ClinVar: RCV000012683, RCV000078374, RCV000384297, RCV000477890, RCV001004934, RCV002251896, RCV002512986, RCV003398488
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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>Scott et al. (1992) found that 31% of MPS I alleles in a study of 64 patients with Hurler syndrome (607014) had a trp402-to-ter (W402X) substitution in the alpha-L-iduronidase protein associated with very severe clinical phenotype in homozygotes. A G-to-A transition at nucleotide 1293 altered the W402 codon (TGG) to a stop codon (TAG); translation was terminated approximately two-thirds of the way through the 653-amino acid IDUA protein. The mutation was originally detected by chemical cleavage and then by direct PCR sequencing. The patients who were compound heterozygotes for the allele had a wide range of clinical phenotypes. Based on polymorphisms within the IDUA gene, Scott et al. (1992) determined that the W402X mutation is associated with 3 different haplotypes, implying more than one origin for the mutation or intragenic recombination. The mutation introduced a MaeI restriction endonuclease site into the gene, thus enabling simple detection of the mutation. Assessment of the efficacy of bone marrow transplantation in patients homozygous for the mutation is thus possible. </p><p>Significantly, the index case of Scheie syndrome (GM1323) reported by McKusick et al. (1965), who had been assumed to be a homozygote for a separate allele at the IDUA locus, was found in fact to be a compound heterozygote for the W402X allele. Biochemically, following the use of 2 different IDUA monoclonal antibodies, GM1323 fibroblasts had no detectable IDUA protein. They had approximately 0.3% of IDUA activity. This IDUA activity must result from a mild mutation in the other MPS I allele present in the patient. Subsequently, with definition of the mutation in the other allele (252800.0004), this proved to be the case. </p><p>Beesley et al. (2001) found that W402X accounted for 45.3% of mutant alleles in their study. </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 HURLER SYNDROME</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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IDUA, GLN70TER
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<br />
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SNP: rs121965020,
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gnomAD: rs121965020,
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ClinVar: RCV000012684, RCV000185562, RCV000185563, RCV000276574, RCV000763532, RCV000790700, RCV001526587, RCV003390671, RCV003488336
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>By chemical cleavage followed by direct PCR sequencing, Scott et al. (1992) detected and characterized a nonsense mutation, a C-to-T transition at nucleotide 296, that altered a gln codon at position 70 (CAG) to a stop codon (TAG). The termination of translation occurred soon after the mature 74-kD amino terminus of the IDUA protein. Using allele-specific oligonucleotides to detect mutations in a group of 73 MPS I patients, the authors found that the Q70X mutation accounted for 15% of all MPS I alleles. The mutation was associated with an extremely severe clinical phenotype in homozygotes. Patients who were compound heterozygotes showed a wide range of clinical phenotypes. </p><p>Beesley et al. (2001) found that Q70X accounted for 15.9% of alleles in their large study. </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 HURLER SYNDROME</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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IDUA, PRO533ARG
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<br />
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SNP: rs121965021,
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gnomAD: rs121965021,
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ClinVar: RCV000012685, RCV000208595, RCV000486848, RCV000763533, RCV001267070, RCV004595880
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>By chemical cleavage analysis followed by direct PCR sequencing, Scott et al. (1992) detected an alteration of the proline at position 533 to an arginine in the alpha-L-iduronidase protein. Using allele-specific oligonucleotides to screen for the mutation in a group of 73 MPS I (607014) patients, they found that the P533R mutation accounted for 3% of alleles. Homozygotes for the P533R mutation showed an extremely severe clinical phenotype; compound heterozygotes showed a wide range of clinical phenotypes. Scott et al. (1992) found that 3 mutations, W402X, Q70X, and P533R, were responsible for 53% of MPS I alleles, which together defined 28% of MPS I genotypes. </p><p>Using fluorescence-assisted mismatch analysis (FAMA) and cycle sequencing of the PCR products, Alif et al. (1999) screened for mutations in the IDUA gene in a group of 13 Moroccan patients with MPS I and their families, including 3 sibs and twin sibs. The P553R mutation, which is rare in Europeans, was identified in 92% of mutant alleles (24 of 26). This was said to be the highest frequency of this mutation detected in patients with Hurler syndrome. None of the patients carried the W402X (252800.0001) or the Q70X (252800.0002) allele, the most common MPS I mutations in Europeans. </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 SCHEIE SYNDROME</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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IDUA, IVS5AS, G-A, -7
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<br />
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SNP: rs762411583,
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gnomAD: rs762411583,
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ClinVar: RCV000012688, RCV000208601, RCV000669065, RCV003137798
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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 the fibroblast strain GM01323 derived from the index case of the Scheie syndrome (607016) reported by McKusick et al. (1965) and in a second cell line, GM01256, Moskowitz et al. (1993) found compound heterozygosity for the same 2 mutations: a G-to-A transition in intron 5, in position -7 from exon 6, and a W402X change (TGG to TAG) in exon 9. The latter mutation, trp402-to-ter (252800.0001), had previously been identified as a common MPS I mutation in the Caucasian population, present in homozygosity in some Hurler patients and in compound heterozygosity in patients with any form of MPS I, including the Scheie patient GM01323 (Scott et al., 1992). Moskowitz et al. (1993) proposed that the intron 5 mutation was responsible for the Scheie phenotype in these 2 patients. The mutation created a new acceptor splice site, causing 5 intronic nucleotides to be inserted into mRNA; this out-of-frame insertion led to an almost immediate termination codon. Additional splicing of transcripts of one or both alleles at some upstream cryptic site(s) was found. Since the normal splice site was not obliterated by the intron 5 mutation, its use would allow the synthesis of some completely normal enzyme. An analogous situation had been encountered in the HEXB gene (268800); mutations that create a new splice site without destroying the old one, thereby permitting expression of some functional beta-hexosaminidase, had been found in a patient with juvenile Sandhoff disease (Nakano and Suzuki, 1989) and in an individual with the asymptomatic 'hexosaminidase Paris' (Dlott et al., 1990) phenotype. Indeed, Ashton et al. (1992) and Scott et al. (1992) found a low level of immunoprecipitable alpha-L-iduronidase activity with normal K(m) and with probably normal specific activity in the Scheie fibroblast cell line GM01323. Although McKusick et al. (1972) suggested that the Scheie syndrome may represent homozygosity for a mild disease allele, based on the paradigm of hemoglobinopathies SS, CC and SC, molecular studies in lysosomal storage diseases, especially the GM2 gangliosidoses (272800) and Gaucher disease (230800), demonstrate the presence of multiple mutant alleles at each disease locus and the occurrence of compound heterozygosity as well as homozygosity in the milder phenotypes. The findings demonstrate that just one allele, if it permits residual enzyme activity, can protect from severe disease (Neufeld, 1991). Scheie syndrome must be genetically heterogeneous inasmuch as 2 other patients with this phenotype did not have the intron 5 allele. One wonders what the homozygote for this IVS5AS mutation might show phenotypically; the abnormalities might be relatively mild and late in onset, if present at all. By chemical cleavage and direct PCR sequencing, Scott et al. (1993) also found the mutation, which they referred to as 678-7g-to-a, in association with W402X in the index case of McKusick et al. (1965). Scott et al. (1993) concluded that since the W402X allele in other combinations is associated with severe disease, the splice acceptor site mutation is likely to be responsible for the mild clinical phenotype because it allows a very small amount of normal mRNA to be produced. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0005 HURLER SYNDROME</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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|
|
IDUA, GLY409ARG AND TER654CYS
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<br />
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SNP: rs11934801, rs199794428,
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gnomAD: rs11934801, rs199794428,
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ClinVar: RCV000012686, RCV000078375, RCV000327434, RCV000418377, RCV000722002
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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 Hurler syndrome (607014) in a consanguineous Muslim Arab family in Gaza, Bach et al. (1993) observed homozygosity for an IDUA allele containing 2 amino acid substitutions: a G-to-C transversion in exon 9 converting codon 409 from GGG (gly) to CGG (arg), and an A-to-T transversion in the termination codon 654 (TGA), converting it to a cys (TGT) residue. The cDNA sequence predicted an extension of 38 amino acids before the next termination codon was reached. Both mutations were found in heterozygous form in the DNA of each parent. Expression of cDNA mutagenized at one or both positions showed that gly409-to-arg caused a reduction of less than half the alpha-L-iduronidase activity, whereas the ter-to-cys mutation reduced activity by 98% compared with expression of normal cDNA. </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 HURLER SYNDROME</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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IDUA, TYR64TER
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<br />
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SNP: rs121965022,
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gnomAD: rs121965022,
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ClinVar: RCV000012689, RCV001851807, RCV003137513
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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>Schaap and Bach (1980) found 13 Arab patients with Hurler syndrome (607014) but only 1 Jewish patient in Israel where ascertainment of the disorder had been complete for 15 years. The mutation in the Jewish patient was the deletion/insertion mutation described by Moskowitz et al. (1993). The Arab patients came from 8 families, 5 of which were Druze and 3 Muslim. Unexpectedly, Bach et al. (1993) found homozygosity for 3 different mutations distributed in 7 families, 5 of them Druze: mutations in exon 2 (tyr64-to-ter), exon 7 (gln310-to-ter; 252800.0007), and exon 8 (thr366-to-pro; 252800.0008). Transfection of mutagenized cDNA into COS-1 cells showed that the missense mutation thr366-to-pro permitted the expression of only trace amounts of alpha-L-iduronidase activity. The nonsense mutations were associated with abnormalities of RNA processing. The tyr64-to-ter mutation was accompanied by a very low level of mRNA and skipping of exon 2. Utilization of a cryptic splice site was observed with the gln310-to-ter mutation. The Druze and Muslim Arab populations have been separated by religion since the inception of the Ismalia or Druze religion in Egypt in the 11th century A.D. At present the Druze live in a defined geographic area of southern Syria, southern Lebanon, and northern Israel; they maintain an isolated social structure with a high rate of consanguineous marriages. The Druze population in Israel numbers about 60,000. Bach et al. (1993) anticipated that MPS in the Druze population would be caused by 1 founder mutation which might or might not be shared with the Muslim patients residing in the surrounding area. They were surprised to find that, in fact, there were 3 different 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>
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<span class="mim-font">
|
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<strong>.0007 HURLER SYNDROME</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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IDUA, GLN310TER
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<br />
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SNP: rs121965023,
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ClinVar: RCV000012690
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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>For discussion of the gln310-to-ter (Q310X) mutation in the IDUA gene that was found in homozygous state in patients with Hurler syndrome (607014) by Bach et al. (1993), see 252800.0006. </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>.0008 HURLER SYNDROME</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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IDUA, THR366PRO
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<br />
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SNP: rs121965024,
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gnomAD: rs121965024,
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ClinVar: RCV000012691
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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>For discussion of the thr366-to-pro (T366P) mutation in the IDUA gene that was found in homozygous state in patients with Hurler syndrome (607014) by Bach et al. (1993), see 252800.0006. </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>.0009 HURLER SYNDROME</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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IDUA, 1-BP DEL, 1702G
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<br />
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SNP: rs727503967,
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gnomAD: rs727503967,
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ClinVar: RCV000173986, RCV000790661, RCV001248893, RCV002498729
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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 a severe form of Hurler syndrome (607014), Scott et al. (1993) found that the Q70X (252800.0002) mutation was combined with an allele carrying a deletion of a single G residue at cDNA base 1702, resulting in a frameshift. </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>.0010 HURLER SYNDROME</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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IDUA, ARG621TER
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|
<br />
|
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|
|
SNP: rs121965025,
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|
|
gnomAD: rs121965025,
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ClinVar: RCV000012692, RCV000780350, RCV001781251, RCV002496329
|
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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>Bunge et al. (1994) identified an R621X mutation due to a CGA-to-TGA transition in a patient with Hurler syndrome (607014). The patient was a compound heterozygote, the other allele being the common W402X mutation (252800.0001). </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>.0011 SCHEIE SYNDROME</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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IDUA, ARG492PRO
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<br />
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|
SNP: rs121965026,
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gnomAD: rs121965026,
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|
ClinVar: RCV000012693, RCV001781252, RCV001851808, RCV004795397
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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 Scheie syndrome (607016), Tieu et al. (1995) found a heterozygous G-to-C transversion in codon 492, corresponding to a change of arginine (CGG) to proline (CCG). The mutation, which created an ApaI site, was inherited from the patient's mother. No alpha-L-iduronidase activity was observed when cDNA containing the R492P mutation was expressed in COS-1 cells. Even though no activity was observed, this mutation must be presumed responsible for the mild Scheie phenotype, because the other allele carried the gln70-to-ter Hurler mutation associated with severe disease (252800.0002). This was the third mutation to be described in the Scheie syndrome; in each case, there was compound heterozygosity for a common Hurler 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">
|
|
<strong>.0012 HURLER-SCHEIE SYNDROME</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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IDUA, LEU490PRO
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<br />
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SNP: rs121965027,
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|
gnomAD: rs121965027,
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|
ClinVar: RCV000012694, RCV000173657, RCV000790664, RCV001204340
|
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|
|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>Tieu et al. (1995) demonstrated that the Hurler/Scheie (607015) cell line GM00512 had a T-to-C transition in codon 490, converting leucine (CTG) to proline (CCG), and creating a SmaI site. No alpha-L-iduronidase activity was detected when cDNA containing the L490P mutation was expressed in COS-1 cells. There was no evidence for heterozygosity either in the genomic sequence or in the restriction digest, suggesting that the mutation was present in homozygous form. However, hemizygosity, because of either deletion of the IDUA gene on 1 chromosome or uniparental disomy, had not been ruled out. The GM00512 cell line was derived from a patient of Asian Indian origin, whose parents were not known to be consanguineous. Homozygosity had been observed previously only in consanguineous families or for the most common mutations, W402X (252800.0001) and Q70X (252800.0002). It is therefore possible that the L490P mutation is relatively common among Indian MPS I patients. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
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|
</div>
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|
</div>
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|
<div>
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 HURLER-SCHEIE SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
IDUA, TER654GLY
|
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|
|
<br />
|
|
|
|
SNP: rs121965028, rs387906504,
|
|
|
|
|
|
|
|
ClinVar: RCV000012695, RCV000208602
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Hurler/Scheie syndrome (607015), Tieu et al. (1995) observed a heterozygous T-to-G transversion in the IDUA gene that changed the termination codon (TGA) to glycine (GGA), which predicted an extension of 38 amino acids at the C terminus of the protein. The mutation, which created a BstNI site, was inherited from the mother. A very low level of alpha-L-iduronidase activity was observed when the mutagenized cDNA was expressed in COS-1 cells. This mutation must have been responsible for the Hurler/Scheie phenotype, as the other allele carried the Q70X Hurler mutation (252800.0002). Another mutation in the termination codon, X654C, had previously been observed in cells of a patient (GM01898) whose phenotype could not be clearly classified as either Hurler or Hurler/Scheie (Bach et al., 1993). </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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|
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<div>
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<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 HURLER SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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<div>
|
|
<span class="mim-text-font">
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|
|
|
IDUA, 5-BP INS, NT704
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|
|
<br />
|
|
|
|
SNP: rs786200915,
|
|
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|
|
|
|
|
ClinVar: RCV000012696, RCV000208610
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the study of 19 Japanese MPS I (607014) patients with various clinical phenotypes, Yamagishi et al. (1996) found that a 5-bp insertion between the T at nucleotide 704 and the C at nucleotide 705 accounted for 7 of 38 alleles (18%). This mutation had not been found in any Caucasian patients. It was associated with a specific haplotype, suggesting to the authors that the individuals with the mutation derived from a common ancestor. Homozygosity of the 704ins5 mutation was associated with a severe phenotype. </p><p>Lee et al. (2004) found the 704ins5 mutation in 4 of 10 unrelated Korean patients with MPS I. All occurred in compound heterozygous state in patients with Hurler syndrome (607014). </p>
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|
</span>
|
|
</div>
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|
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|
<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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<div>
|
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 HURLER-SCHEIE SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
HURLER SYNDROME, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
IDUA, ARG89GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121965029,
|
|
|
|
|
|
gnomAD: rs121965029,
|
|
|
|
|
|
ClinVar: RCV000012697, RCV000169784, RCV000208598, RCV005042034
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the study of 19 Japanese MPS I patients with various clinical phenotypes, Yamagishi et al. (1996) found that the R89Q mutation accounted for 9 of 38 alleles (24%). Homozygosity for the R89Q mutation was associated with a mild phenotype. Compound heterozygosity for this and the 704ins5 mutation (252800.0014) produced an intermediate phenotype (607015). Haplotype analysis using polymorphisms linked to the IDUA locus demonstrated that the mutation occurred on a specific haplotype, suggesting to the authors that individuals with the mutation derived from a common ancestor. Of 3 homozygotes, 1 died of congestive heart failure at the age of 48 years. One of the heterozygotes died of the same at 31 years. She was 117 cm tall. Scott et al. (1993) had previously described the R89Q mutation in compound heterozygous state with the W402X mutation (252800.0001) in Caucasian Hurler syndrome (607014) patients. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 IDUA PSEUDODEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
IDUA, ALA300THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121965030,
|
|
|
|
|
|
|
|
ClinVar: RCV000012698, RCV000667026, RCV001206227, RCV003129751
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a healthy female, Aronovich et al. (1996) found compound heterozygosity for the W402X mutation (252800.0001) and a new IDUA mutation, A300T. Although fibroblasts from the patient demonstrated normal glycosaminoglycan metabolism, enzyme studies using artificial substrate showed very low levels of alpha-L-iduronidase activity. This was said to have been the first IDUA pseudodeficiency gene to be elucidated at the molecular level. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 HURLER-SCHEIE SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
IDUA, ARG619GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121965031,
|
|
|
|
|
|
gnomAD: rs121965031,
|
|
|
|
|
|
ClinVar: RCV000012699, RCV000666715, RCV003591628
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 18-year-old Chinese patient with an intermediate phenotype consistent with Hurler/Scheie syndrome (607015), Lee-Chen et al. (1999) identified homozygosity for an arg619-to-gly (R619G) mutation due to a C-to-G transversion at nucleotide 1943. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 HURLER-SCHEIE SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
IDUA, THR364MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121965032,
|
|
|
|
|
|
|
|
ClinVar: RCV000012700, RCV000588505, RCV000984188, RCV003488337, RCV005031435
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Lee-Chen and Wang (1997) identified homozygosity for a thr364-to-met (T364M) mutation in the IDUA gene product in a 10-year-old Chinese patient with the Hurler/Scheie syndrome (607015). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 HURLER-SCHEIE SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
IDUA, IVS2AS, C-G, -3
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1226056948,
|
|
|
|
|
|
gnomAD: rs1226056948,
|
|
|
|
|
|
ClinVar: RCV000012701, RCV000666654, RCV001043397
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Chinese patient with Hurler/Scheie syndrome (607015), Teng et al. (2000) identified compound heterozygosity for a maternal allele with a leu346-to-arg (L346R; 252800.0020) mutation (T-to-G transversion in codon 346) and a paternal allele with a C-to-G transversion at position -3 of the 3-prime splice acceptor site of intron 2. In transfected COS-7 cells, L346R showed no appreciable IDUA activity, although it did not cause an apparent reduction in IDUA mRNA or protein level. The splice acceptor site mutation profoundly affected normal splicing leading to a very unstable mRNA. Expression of IDUA cDNA containing the mutated acceptor splice site showed trace amounts of enzyme activity (1.6% of normal activity). The results provided further support for the importance of cytosine at the -3 position in RNA processing. The patient reported by Teng et al. (2000) was 12 years old with short stature, macrocephaly, coarse face, corneal clouding, skeletal deformities, and hepatosplenomegaly, but normal intelligence. Other mild clinical features included hearing impairment, tracheal stenosis, hypertrophic cardiomyopathy, obstructive-type sleep apnea, adenoid hyperplasia, tonsil hypertrophy, umbilical hernia, anemia, </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 HURLER-SCHEIE SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
HURLER SYNDROME, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
IDUA, LEU346ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121965033,
|
|
|
|
|
|
gnomAD: rs121965033,
|
|
|
|
|
|
ClinVar: RCV000012702, RCV000012703, RCV001248726, RCV005042035
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the leu346-to-arg (L346R) mutation in the IDUA gene that was found in compound heterozygous state in a patient with Hurler/Scheie syndrome (607015) by Teng et al. (2000), see 252800.0019. </p><p>Lee et al. (2004) found the L346R mutation in 6 of 10 unrelated Korean patients with MPS I, 4 with Hurler syndrome (607014) and 2 with Hurler/Scheie syndrome. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Clements et al. (1985); Clements et al. (1985)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Alif, N., Hess, K., Straczek, J., Sebbar, S., N'Bou, A., Nabet, P., Dousset, B.
|
|
<strong>Mucopolysaccharidosis type I: characterization of a common mutation that causes Hurler syndrome in Moroccan subjects.</strong>
|
|
Ann. Hum. Genet. 63: 9-16, 1999.
|
|
|
|
|
|
[PubMed: 10738517]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1469-1809.1999.6310009.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Aronovich, E. L., Pan, D., Whitley, C. B.
|
|
<strong>Molecular genetic defect underlying alpha-L-iduronidase pseudodeficiency.</strong>
|
|
Am. J. Hum. Genet. 58: 75-85, 1996.
|
|
|
|
|
|
[PubMed: 8554071]
|
|
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ashton, L. J., Brooks, D. A., McCourt, P. A. G., Muller, V. J., Clements, P. R., Hopwood, J. J.
|
|
<strong>Immunoquantification and enzyme kinetics of alpha-L-iduronidase in cultured fibroblasts from normal controls and mucopolysaccharidosis type I patients.</strong>
|
|
Am. J. Hum. Genet. 50: 787-794, 1992.
|
|
|
|
|
|
[PubMed: 1550122]
|
|
|
|
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|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
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<p class="mim-text-font">
|
|
Bach, G., Moskowitz, S. M., Tieu, P. T., Matynia, A., Neufeld, E. F.
|
|
<strong>Molecular analysis of Hurler syndrome in Druze and Muslim Arab patients in Israel: multiple allelic mutations of the IDUA gene in a small geographic area.</strong>
|
|
Am. J. Hum. Genet. 53: 330-338, 1993.
|
|
|
|
|
|
[PubMed: 8328452]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Barton, R. W., Neufeld, E. F.
|
|
<strong>The Hurler corrective factor: purification and some properties.</strong>
|
|
J. Biol. Chem. 246: 7773-7779, 1971.
|
|
|
|
|
|
[PubMed: 4257494]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Beesley, C. E., Meaney, C. A., Greenland, G., Adams, V., Vellodi, A., Young, E. P., Winchester, B. G.
|
|
<strong>Mutational analysis of 85 mucopolysaccharidosis type I families: frequency of known mutations, identification of 17 novel mutations and in vitro expression of missense mutations.</strong>
|
|
Hum. Genet. 109: 503-511, 2001.
|
|
|
|
|
|
[PubMed: 11735025]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390100606]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bunge, S., Kleijer, W. J., Steglich, C., Beck, M., Schwinger, E., Gal, A.
|
|
<strong>Mucopolysaccharidosis type I: identification of 13 novel mutations of the alpha-L-iduronidase gene.</strong>
|
|
Hum. Mutat. 6: 91-94, 1995.
|
|
|
|
|
|
[PubMed: 7550242]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1380060119]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bunge, S., Kleijer, W. J., Steglich, C., Beck, M., Zuther, C., Morris, C. P., Schwinger, E., Hopwood, J. J., Scott, H. S., Gal, A.
|
|
<strong>Mucopolysaccharidosis type I: identification of 8 novel mutations and determination of the frequency of the two common alpha-L-iduronidase mutations (W402X and Q70X) among European patients.</strong>
|
|
Hum. Molec. Genet. 3: 861-866, 1994.
|
|
|
|
|
|
[PubMed: 7951228]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/3.6.861]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Clarke, L. A., Giugliani, R., Guffon, N., Jones, S. A., Keenan, H. A., Munoz-Rojas, M. V., Okuyama, T., Viskochil, D., Whitley, C. B., Wijburg, F. R., Muenzer, J.
|
|
<strong>Genotype-phenotype relationships in mucopolysaccharidosis type I (MPS I): insights from the International MPS I Registry.</strong>
|
|
Clin. Genet. 96: 281-289, 2019.
|
|
|
|
|
|
[PubMed: 31194252]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/cge.13583]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Clements, P. R., Brooks, D. A., McCourt, P. A. G., Hopwood, J. J.
|
|
<strong>Immunopurification and characterization of human alpha-L-iduronidase with the use of monoclonal antibodies.</strong>
|
|
Biochem. J. 259: 199-208, 1989.
|
|
|
|
|
|
[PubMed: 2470345]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1042/bj2590199]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Clements, P. R., Brooks, D. A., Saccone, G. T. P., Hopwood, J. J.
|
|
<strong>Human alpha-L-iduronidase: 1. Purification, monoclonal antibody production, native and subunit molecular mass.</strong>
|
|
Europ. J. Biochem. 152: 21-28, 1985.
|
|
|
|
|
|
[PubMed: 4043081]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1432-1033.1985.tb09158.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Clements, P. R., Muller, V., Hopwood, J. J.
|
|
<strong>Human alpha-L-iduronidase: 2. Catalytic properties.</strong>
|
|
Europ. J. Biochem. 152: 29-34, 1985.
|
|
|
|
|
|
[PubMed: 4043083]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1432-1033.1985.tb09159.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dlott, B., d'Azzo, A., Quon, D. V. K., Neufeld, E. F.
|
|
<strong>Two mutations produce intron insertion in mRNA and elongated beta-subunits of human beta-hexosaminidase.</strong>
|
|
J. Biol. Chem. 265: 17921-17927, 1990.
|
|
|
|
|
|
[PubMed: 2170400]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gatti, R., DiNatale, P., Villani, G. R. D., Filocamo, M., Muller, V., Guo, X.-H., Nelson, P. V., Scott, H. S., Hopwood, J. J.
|
|
<strong>Mutations among Italian mucopolysaccharidosis type I patients.</strong>
|
|
J. Inherit. Metab. Dis. 20: 803-806, 1997.
|
|
|
|
|
|
[PubMed: 9427149]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1023/a:1005323918923]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Grosson, C. L. S., MacDonald, M. E., Duyao, M. P., Ambrose, C. M., Roffler-Tarlov, S., Gusella, J. F.
|
|
<strong>Synteny conservation of the Huntington's disease gene and surrounding loci on mouse chromosome 5.</strong>
|
|
Mammalian Genome 5: 424-428, 1994.
|
|
|
|
|
|
[PubMed: 7919654]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00357002]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lee, I. J., Hwang, S. H., Jeon, B. H., Song, S. M., Kim, J. S., Paik, K. H., Kwon, E. K., Jin, D.-K.
|
|
<strong>Mutational analysis of the alpha-L-iduronidase gene in 10 unrelated Korean type I mucopolysaccharidosis patients: identification of four novel mutations. (Letter)</strong>
|
|
Clin. Genet. 66: 575-576, 2004.
|
|
|
|
|
|
[PubMed: 15521993]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2004.00374.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lee-Chen, G. J., Lin, S. P., Tang, Y. F., Chin, Y. W.
|
|
<strong>Mucopolysaccharidosis type I: characterization of novel mutations affecting alpha-L-iduronidase activity.</strong>
|
|
Clin. Genet. 56: 66-70, 1999.
|
|
|
|
|
|
[PubMed: 10466419]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.1999.560109.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lee-Chen, G. J., Wang, T. R.
|
|
<strong>Mucopolysaccharidosis type I: identification of novel mutations that cause Hurler/Scheie syndrome in Chinese families.</strong>
|
|
J. Med. Genet. 34: 939-941, 1997.
|
|
|
|
|
|
[PubMed: 9391892]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.34.11.939]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Li, P., Wood, T., Thompson, J. N.
|
|
<strong>Diversity of mutations and distribution of single nucleotide polymorphic alleles in the human alpha-L-iduronidase (IDUA) gene.</strong>
|
|
Genet. Med. 4: 420-426, 2002.
|
|
|
|
|
|
[PubMed: 12509712]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/00125817-200211000-00004]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McKusick, V. A., Howell, R. R., Hussels, I. E., Neufeld, E. F., Stevenson, R. E.
|
|
<strong>Allelism, nonallelism and genetic compounds among the mucopolysaccharidoses.</strong>
|
|
Lancet 299: 993-996, 1972. Note: Originally Volume I.
|
|
|
|
|
|
[PubMed: 4112371]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(72)91159-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McKusick, V. A., Kaplan, D., Wise, D., Hanley, W. B., Suddarth, S. B., Sevick, M. E., Maumanee, A. W.
|
|
<strong>The genetic mucopolysaccharidoses.</strong>
|
|
Medicine 44: 445-483, 1965.
|
|
|
|
|
|
[PubMed: 4221470]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/00005792-196511000-00001]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Menon, K. P., Tieu, P. T., Neufeld, E. F.
|
|
<strong>Architecture of the canine IDUA gene and mutation underlying canine mucopolysaccharidosis I.</strong>
|
|
Genomics 14: 763-768, 1992.
|
|
|
|
|
|
[PubMed: 1339393]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0888-7543(05)80182-x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Moskowitz, S. M., Tieu, P. T., Neufeld, E. F.
|
|
<strong>A deletion/insertion mutation in the IDUA gene in a Libyan Jewish patient with Hurler syndrome (mucopolysaccharidosis IH).</strong>
|
|
Hum. Mutat. 2: 71-73, 1993.
|
|
|
|
|
|
[PubMed: 8477267]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1380020113]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Moskowitz, S. M., Tieu, P. T., Neufeld, E. F.
|
|
<strong>Mutation in Scheie syndrome (MPS IS): a G-to-A transition creates new splice site in intron 5 of one IDUA allele.</strong>
|
|
Hum. Mutat. 2: 141-144, 1993.
|
|
|
|
|
|
[PubMed: 8318992]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1380020215]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nakano, T., Suzuki, K.
|
|
<strong>Genetic cause of a juvenile form of Sandhoff disease: abnormal splicing of beta-hexosaminidase beta-chain gene transcript due to a point mutation within intron 12.</strong>
|
|
J. Biol. Chem. 264: 5155-5158, 1989.
|
|
|
|
|
|
[PubMed: 2522450]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Neufeld, E. F., Muenzer, J.
|
|
<strong>The mucopolysaccharidoses. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic & Molecular Bases of Inherited Disease. Vol. II. (8th ed.)</strong>
|
|
New York: McGraw-Hill (pub.) 2001.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Neufeld, E. F.
|
|
<strong>Lysosomal storage diseases.</strong>
|
|
Annu. Rev. Biochem. 60: 257-280, 1991.
|
|
|
|
|
|
[PubMed: 1883197]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1146/annurev.bi.60.070191.001353]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schaap, T., Bach, G.
|
|
<strong>Incidence of mucopolysaccharidoses in Israel: is Hunter disease a 'Jewish disease'?</strong>
|
|
Hum. Genet. 56: 221-223, 1980.
|
|
|
|
|
|
[PubMed: 6821579]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00295699]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schuchman, E. H., Astrin, K. H., Aula, P., Desnick, R. J.
|
|
<strong>Gene assignment for human alpha-L-iduronidase. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 34: 175A, 1982.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schuchman, E. H., Astrin, K. H., Aula, P., Desnick, R. J.
|
|
<strong>Regional assignment of the structural gene for human alpha-L-iduronidase.</strong>
|
|
Proc. Nat. Acad. Sci. 81: 1169-1173, 1984.
|
|
|
|
|
|
[PubMed: 6422468]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.81.4.1169]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scott, H. S., Anson, D. S., Orsborn, A. M., Nelson, P. V., Clements, P. R., Morris, C. P., Hopwood, J. J.
|
|
<strong>Human alpha-L-iduronidase: cDNA isolation and expression.</strong>
|
|
Proc. Nat. Acad. Sci. 88: 9695-9699, 1991.
|
|
|
|
|
|
[PubMed: 1946389]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.88.21.9695]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scott, H. S., Ashton, L. J., Eyre, H. J., Baker, E., Brooks, D. A., Callen, D. F., Sutherland, G. R., Morris, C. P., Hopwood, J. J.
|
|
<strong>Chromosomal localization of the human alpha-L-iduronidase gene (IDUA) to 4p16.3.</strong>
|
|
Am. J. Hum. Genet. 47: 802-807, 1990.
|
|
|
|
|
|
[PubMed: 2220820]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scott, H. S., Bunge, S., Gal, A., Clarke, L. A., Morris, C. P., Hopwood, J. J.
|
|
<strong>Molecular genetics of mucopolysaccharidosis type I: diagnostic, clinical, and biological implications.</strong>
|
|
Hum. Mutat. 6: 288-302, 1995.
|
|
|
|
|
|
[PubMed: 8680403]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1380060403]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scott, H. S., Guo, X.-H., Hopwood, J. J., Morris, C. P.
|
|
<strong>Structure and sequence of the human alpha-L-iduronidase gene.</strong>
|
|
Genomics 13: 1311-1313, 1992.
|
|
|
|
|
|
[PubMed: 1505961]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(92)90053-u]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scott, H. S., Litjens, T., Hopwood, J. J., Morris, C. P.
|
|
<strong>A common mutation for mucopolysaccharidosis type I associated with a severe Hurler syndrome phenotype.</strong>
|
|
Hum. Mutat. 1: 103-108, 1992.
|
|
|
|
|
|
[PubMed: 1301196]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1380010204]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scott, H. S., Litjens, T., Nelson, P. V., Brooks, D. A., Hopwood, J. J., Morris, C. P.
|
|
<strong>Alpha-L-iduronidase mutations (Q70X and P533R) associate with a severe Hurler phenotype.</strong>
|
|
Hum. Mutat. 1: 333-339, 1992.
|
|
|
|
|
|
[PubMed: 1301941]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1380010412]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scott, H. S., Litjens, T., Nelson, P. V., Thompson, P. R., Brooks, D. A., Hopwood, J. J., Morris, C. P.
|
|
<strong>Identification of mutations in the alpha-L-iduronidase gene (IDUA) that cause Hurler and Scheie syndromes.</strong>
|
|
Am. J. Hum. Genet. 53: 973-986, 1993.
|
|
|
|
|
|
[PubMed: 8213840]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scott, H. S., Nelson, P. V., MacDonald, M. E., Gusella, J. F., Hopwood, J. J., Morris, C. P.
|
|
<strong>An 86-bp VNTR within IDUA is the basis of the D4S111 polymorphic locus.</strong>
|
|
Genomics 14: 1118-1120, 1992.
|
|
|
|
|
|
[PubMed: 1478658]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0888-7543(05)80145-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stoltzfus, L. J., Sosa-Pineda, B., Moskowitz, S. M., Menon, K. P., Dlott, B., Hooper, L., Teplow, D. B., Shull, R. M., Neufeld, E. F.
|
|
<strong>Cloning and characterization of cDNA encoding canine alpha-L-iduronidase: mRNA deficiency in mucopolysaccharidosis I dog.</strong>
|
|
J. Biol. Chem. 267: 6570-6575, 1992.
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|
|
[PubMed: 1551868]
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Teng, Y. N., Wang, T. R., Hwu, W. L., Lin, S. P., Lee-Chen, G. J.
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<strong>Identification and characterization of -3c-g acceptor splice site mutation in human alpha-L-iduronidase associated with mucopolysaccharidosis type IH/S.</strong>
|
|
Clin. Genet. 57: 131-136, 2000.
|
|
|
|
|
|
[PubMed: 10735634]
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[Full Text: https://doi.org/10.1034/j.1399-0004.2000.570207.x]
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Tieu, P. T., Bach, G., Matynia, A., Hwang, M., Neufeld, E. F.
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<strong>Four novel mutations underlying mild or intermediate forms of alpha-L-iduronidase deficiency (MPS IS and MPS IH/S).</strong>
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Hum. Mutat. 6: 55-59, 1995.
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[PubMed: 7550232]
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[Full Text: https://doi.org/10.1002/humu.1380060111]
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Yamagishi, A., Tomatsu, S., Fukuda, S., Uchiyama, A., Shimozawa, N., Suzuki, Y., Kondo, N., Sukegawa, K., Orii, T.
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<strong>Mucopolysaccharidosis type I: identification of common mutations that cause Hurler and Scheie syndromes in Japanese populations.</strong>
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Hum. Mutat. 7: 23-29, 1996.
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[PubMed: 8664897]
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[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1996)7:1<23::AID-HUMU3>3.0.CO;2-Q]
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Hilary J. Vernon - updated : 09/08/2020<br>Victor A. McKusick - updated : 3/31/2005<br>Victor A. McKusick - updated : 2/9/2004<br>Victor A. McKusick - updated : 11/18/2003<br>Kelly A. Przylepa - reorganized : 10/13/2003<br>Kelly A. Przylepa - updated : 10/13/2003<br>Victor A. McKusick - updated : 12/6/2001<br>George E. Tiller - updated : 4/19/2001<br>Victor A. McKusick - updated : 2/1/2001<br>Victor A. McKusick - updated : 4/21/2000<br>Sonja A. Rasmussen - updated : 3/2/2000<br>Victor A. McKusick - updated : 11/1/1999<br>Victor A. McKusick - updated : 9/8/1999<br>Victor A. McKusick - updated : 8/23/1999<br>Victor A. McKusick - updated : 3/12/1999<br>Victor A. McKusick - updated : 6/12/1998<br>Victor A. McKusick - updated : 2/19/1998<br>Victor A. McKusick - updated : 5/16/1997
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Victor A. McKusick : 6/4/1986
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