4314 lines
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Entry
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- *610453 - HEPARAN-ALPHA-GLUCOSAMINIDE N-ACETYLTRANSFERASE; HGSNAT
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- OMIM
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<p>
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<span class="h4">*610453</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<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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<a href="#geneFunction">Gene Function</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/610453">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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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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<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=ENSG00000165102;t=ENST00000379644" 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=138050" 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=610453" 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 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=ENSG00000165102;t=ENST00000379644" 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_001363227,NM_001363228,NM_001363229,NM_152419,XM_005273409,XM_005273411,XM_005273412,XM_047421388" 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_152419" 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=610453" 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=19408&isoform_id=19408_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/HGSNAT" 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/10438550,15214648,16552925,27469769,48146821,51491261,124007195,150378452,194385774,530387583,530387587,530387589,1388876106,1388876108,1389109256,2217370855,2462617845,2462617847,2462617849,2462617851" 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/Q68CP4" 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=138050" 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=ENSG00000165102;t=ENST00000379644" 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=HGSNAT" 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=HGSNAT" 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+138050" 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/HGSNAT" 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:138050" 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/138050" 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=chr8&hgg_gene=ENST00000379644.9&hgg_start=43140464&hgg_end=43202855&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:26527" 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:26527" 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/hgsnat" 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=610453[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=610453[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/HGSNAT/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/ENSG00000165102" 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=HGSNAT" 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=HGSNAT" 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=HGSNAT" 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/HGSNAT" 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=HGSNAT&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/PA162390851" 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:26527" 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/FBgn0029737.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:1196297" 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/HGSNAT#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:1196297" 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/138050/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://www.orthodb.org/?ncbi=138050" 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-140106-144" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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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:138050" 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=HGSNAT&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> 75238000<br />
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<strong>ICD10CM:</strong> E76.22<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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610453
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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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HEPARAN-ALPHA-GLUCOSAMINIDE N-ACETYLTRANSFERASE; HGSNAT
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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">
|
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TRANSMEMBRANE PROTEIN 76; TMEM76
|
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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">
|
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=HGSNAT" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">HGSNAT</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>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/8/244?start=-3&limit=10&highlight=244">8p11.21-p11.1</a>
|
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr8:43140464-43202855&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'})">8:43,140,464-43,202,855</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
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</div>
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<div>
|
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<br />
|
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</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>
|
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<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=252930,616544" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/8/244?start=-3&limit=10&highlight=244">
|
|
8p11.21-p11.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Mucopolysaccharidosis type IIIC (Sanfilippo C)
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/252930"> 252930 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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</tr>
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
Retinitis pigmentosa 73
|
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|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/616544"> 616544 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
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<p>The HGSNAT gene encodes heparan acetyl-CoA:alpha-glucosaminide N-acetyltransferase (<a href="https://enzyme.expasy.org/EC/2.3.1.78" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 2.3.1.78</a>), an enzyme that catalyzes acetylation of the terminal glucosamine residues of heparan sulfate prior to its hydrolysis by alpha-N-acetyl glucosaminidase (summary by <a href="#10" class="mim-tip-reference" title="Klein, U., Kresse, H., von Figura, K. <strong>Sanfilippo syndrome type C: deficiency of acetyl-CoA: alpha-glucosaminide N-acetyltransferase in skin fibroblasts.</strong> Proc. Nat. Acad. Sci. 75: 5185-5189, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33384</a>] [<a href="https://doi.org/10.1073/pnas.75.10.5185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33384">Klein et al., 1978</a>). The enzyme is sometimes referred to as N-acetyltransferase (<a href="#5" class="mim-tip-reference" title="Fan, X., Zhang, H., Zhang, S., Bagshaw, R. D., Tropak, M. B., Callahan, J. W., Mahuran, D. J. <strong>Identification of the gene encoding the enzyme deficient in mucopolysaccharidosis IIIC (Sanfilippo disease type C).</strong> Am. J. Hum. Genet. 79: 738-744, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16960811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16960811</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16960811[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16960811">Fan et al., 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=33384+16960811" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="#5" class="mim-tip-reference" title="Fan, X., Zhang, H., Zhang, S., Bagshaw, R. D., Tropak, M. B., Callahan, J. W., Mahuran, D. J. <strong>Identification of the gene encoding the enzyme deficient in mucopolysaccharidosis IIIC (Sanfilippo disease type C).</strong> Am. J. Hum. Genet. 79: 738-744, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16960811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16960811</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16960811[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16960811">Fan et al. (2006)</a> identified the gene encoding heparan acetyl-CoA:alpha-glucosaminide N-acetyltransferase, the enzyme defective in mucopolysaccharidosis IIIC, also known as Sanfilippo syndrome type C (<a href="/entry/252930">252930</a>) (<a href="#10" class="mim-tip-reference" title="Klein, U., Kresse, H., von Figura, K. <strong>Sanfilippo syndrome type C: deficiency of acetyl-CoA: alpha-glucosaminide N-acetyltransferase in skin fibroblasts.</strong> Proc. Nat. Acad. Sci. 75: 5185-5189, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33384</a>] [<a href="https://doi.org/10.1073/pnas.75.10.5185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33384">Klein et al., 1978</a>). In a proteomics study of mouse lysosomal membrane proteins, <a href="#5" class="mim-tip-reference" title="Fan, X., Zhang, H., Zhang, S., Bagshaw, R. D., Tropak, M. B., Callahan, J. W., Mahuran, D. J. <strong>Identification of the gene encoding the enzyme deficient in mucopolysaccharidosis IIIC (Sanfilippo disease type C).</strong> Am. J. Hum. Genet. 79: 738-744, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16960811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16960811</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16960811[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16960811">Fan et al. (2006)</a> identified an unknown protein whose human homolog, TMEM76, was encoded by a gene that maps to 8p11.1. They expressed a full-length mouse expressed sequence tag (EST) in human MPS IIIC fibroblasts and observed that its protein product localized to the lysosome and corrected the enzymatic defect. <a href="#5" class="mim-tip-reference" title="Fan, X., Zhang, H., Zhang, S., Bagshaw, R. D., Tropak, M. B., Callahan, J. W., Mahuran, D. J. <strong>Identification of the gene encoding the enzyme deficient in mucopolysaccharidosis IIIC (Sanfilippo disease type C).</strong> Am. J. Hum. Genet. 79: 738-744, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16960811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16960811</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16960811[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16960811">Fan et al. (2006)</a> used the mouse sequence to identify the full-length human homolog, HGSNAT. The deduced C-terminal portion of HGSNAT is highly conserved across species, including plants and bacteria; however, the N-terminal portion, extending to transmembrane domain B, is found only in metazoans. Neither of these regions has homology with functional domains identified elsewhere, including those from proteins known to bind CoA or acetyl-CoA; therefore, HGSNAT represents the human member of a new family of enzymes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=33384+16960811" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By examining candidate genes in the region of chromosome 8 associated with MPS IIIC, <a href="#9" class="mim-tip-reference" title="Hrebicek, M., Mrazova, L., Seyrantepe, V., Durand, S., Roslin, N. M., Noskova, L., Hartmannova, H., Ivanek, R., Cizkova, A., Poupetova, H., Sikora, J., Urinovska, J., and 18 others. <strong>Mutations in TMEM76 cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome).</strong> Am. J. Hum. Genet. 79: 807-819, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033958</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033958[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508294" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17033958">Hrebicek et al. (2006)</a> identified HGSNAT, which they called TMEM76. The deduced 656-amino acid protein with a calculated molecular mass of 73 kD contains an N-terminal signal peptide, 4 putative N-glycosylation sites, and 11 transmembrane domains. Topology modeling predicted the N terminus to be inside the lysosome and the C terminus to be cytosolic. <a href="#9" class="mim-tip-reference" title="Hrebicek, M., Mrazova, L., Seyrantepe, V., Durand, S., Roslin, N. M., Noskova, L., Hartmannova, H., Ivanek, R., Cizkova, A., Poupetova, H., Sikora, J., Urinovska, J., and 18 others. <strong>Mutations in TMEM76 cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome).</strong> Am. J. Hum. Genet. 79: 807-819, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033958</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033958[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508294" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17033958">Hrebicek et al. (2006)</a> also identified a splice variant lacking exons 9 and 10 that encodes a protein with an in-frame deletion of 64 amino acids in transmembrane domains 3 and 4. This variant was considered likely to encode an inactive enzyme since it was detected in the RNA of 3 MPS IIIC patients with nearly complete loss of N-acetyltransferase activity. Northern blot analysis detected ubiquitous expression of 4.5- and 2.1-kb transcripts. Highest expression was in leukocytes, heart, lung, placenta, and liver, and much lower expression was found in thymus, colon, and brain. RT-PCR detected TMEM76 in normal human skin, fibroblasts, white blood cells, and skeletal muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17033958" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#8" class="mim-tip-reference" title="Haer-Wigman, L., Newman, H., Leibu, R., Bax, N. M., Baris, H. N., Rizel, L., Banin, E., Massarweh, A., Roosing, S., Lefeber, D. J., Zonneveld-Vrieling, M. N., Isakov, O., Shomron, N., Sharon, D., Den Hollander, A. I., Hoyng, C. B., Cremers, F. P. M., Ben-Yosef, T. <strong>Non-syndromic retinitis pigmentosa due to mutations in the mucopolysaccharidosis type IIIC gene, heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT).</strong> Hum. Molec. Genet. 24: 3742-3751, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25859010/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25859010</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25859010[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddv118" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25859010">Haer-Wigman et al. (2015)</a> performed RT-PCR analysis of HGSNAT RNA derived from normal human retina and leukocytes. Both tissues yielded the expected product, but the authors noted that obtaining a product from leukocytes required an additional set of amplification, indicating that HGSNAT expression levels in the retina are much higher than those in blood leukocytes. RT-PCR analysis of total RNA from mouse eye showed Hgsnat expression as early as embryonic day 14, with equally high expression levels after birth, at postnatal days 0 and 30. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25859010" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>N-acetyltransferase is a lysosomal membrane enzyme whose function is to acetylate the nonreducing, terminal alpha-glucosamine residue of intralysosomal heparin or heparan sulfate, converting it into a substrate for luminal alpha-N-acetylglucosaminidase (<a href="#5" class="mim-tip-reference" title="Fan, X., Zhang, H., Zhang, S., Bagshaw, R. D., Tropak, M. B., Callahan, J. W., Mahuran, D. J. <strong>Identification of the gene encoding the enzyme deficient in mucopolysaccharidosis IIIC (Sanfilippo disease type C).</strong> Am. J. Hum. Genet. 79: 738-744, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16960811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16960811</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16960811[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16960811">Fan et al., 2006</a>). Therefore, N-acetyltransferase catalyzes the only synthetic reaction known to occur in the lysosome. To do this, the enzyme uses a cytosolic cofactor, acetyl-coenzyme A (acetyl-CoA). Thus, its substrate and cofactor are separated by the lysosomal membrane. The mechanism by which this spatial problem is overcome is controversial. One model suggests a ping-pong mechanism involving an initial acetylation reaction of the enzyme in the cytosol, followed by a transfer of the acetyl group to the intralysosomal heparin-alpha-glucosamine residue (<a href="#2" class="mim-tip-reference" title="Bame, K. J., Rome, L. H. <strong>Genetic evidence for transmembrane acetylation by lysosomes.</strong> Science 233: 1087-1089, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3090688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3090688</a>] [<a href="https://doi.org/10.1126/science.3090688" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3090688">Bame and Rome, 1986</a>; <a href="#1" class="mim-tip-reference" title="Ausseil, J., Landry, K., Seyrantepe, V., Trudel, S., Mazur, A., Lapointe, F., Pshezhetsky, A. V. <strong>An acetylated 120-kDa lysosomal transmembrane protein is absent from mucopolysaccharidosis IIIC fibroblasts: a candidate molecule for MPS IIIC.</strong> Molec. Genet. Metab. 87: 22-31, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16293432/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16293432</a>] [<a href="https://doi.org/10.1016/j.ymgme.2005.09.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16293432">Ausseil et al., 2006</a>). An alternative model proposes that the enzyme operates via a random order ternary complex mechanism; that is, there is no acetylated enzyme intermediate (<a href="#11" class="mim-tip-reference" title="Meikle, P. J., Whittle, A. M., Hopwood, J. J. <strong>Human acetyl-coenzyme A:alpha-glucosaminide N-acetyltransferase: kinetic characterization and mechanistic interpretation.</strong> Biochem. J. 308: 327-333, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7755582/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7755582</a>] [<a href="https://doi.org/10.1042/bj3080327" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7755582">Meikle et al., 1995</a>). The enzyme, which proved difficult to purify, is believed to be a dimer of 120 kD subunits containing asn-linked oligosaccharides. It is also postulated that the 120-kD subunit may be only the catalytic subunit of a protein complex whose other unidentified members are also required for functionality. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7755582+3090688+16293432+16960811" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#9" class="mim-tip-reference" title="Hrebicek, M., Mrazova, L., Seyrantepe, V., Durand, S., Roslin, N. M., Noskova, L., Hartmannova, H., Ivanek, R., Cizkova, A., Poupetova, H., Sikora, J., Urinovska, J., and 18 others. <strong>Mutations in TMEM76 cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome).</strong> Am. J. Hum. Genet. 79: 807-819, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033958</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033958[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508294" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17033958">Hrebicek et al. (2006)</a> performed functional expression of human HGSNAT and the mouse ortholog and demonstrated that it is the gene that encodes the lysosomal N-acetyltransferase. HGSNAT did not show structural similarity to any known prokaryotic or eukaryotic N-acetyltransferase or to other lysosomal proteins, on the basis of sequence homology searches. The authors suggested that this enzyme belongs to a new structural class of proteins that transport the activated acetyl residues across the cell membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17033958" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="#5" class="mim-tip-reference" title="Fan, X., Zhang, H., Zhang, S., Bagshaw, R. D., Tropak, M. B., Callahan, J. W., Mahuran, D. J. <strong>Identification of the gene encoding the enzyme deficient in mucopolysaccharidosis IIIC (Sanfilippo disease type C).</strong> Am. J. Hum. Genet. 79: 738-744, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16960811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16960811</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16960811[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16960811">Fan et al. (2006)</a> demonstrated that the HGSNAT gene contains 18 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16960811" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="#5" class="mim-tip-reference" title="Fan, X., Zhang, H., Zhang, S., Bagshaw, R. D., Tropak, M. B., Callahan, J. W., Mahuran, D. J. <strong>Identification of the gene encoding the enzyme deficient in mucopolysaccharidosis IIIC (Sanfilippo disease type C).</strong> Am. J. Hum. Genet. 79: 738-744, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16960811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16960811</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16960811[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16960811">Fan et al. (2006)</a> identified the HGSNAT gene on chromosome 8p11.1 by comparison of mouse and human sequences. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16960811" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Mucopolysaccharidosis IIIC</em></strong></p><p>
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Mucopolysaccharidosis IIIC (MPS3C), or Sanfilippo syndrome type C (<a href="/entry/252930">252930</a>), is an autosomal recessive disorder characterized by the lysosomal storage of heparin and heparan sulfate. The hallmark of the Sanfilippo syndrome is severe central nervous system involvement but only mild somatic disease. <a href="#5" class="mim-tip-reference" title="Fan, X., Zhang, H., Zhang, S., Bagshaw, R. D., Tropak, M. B., Callahan, J. W., Mahuran, D. J. <strong>Identification of the gene encoding the enzyme deficient in mucopolysaccharidosis IIIC (Sanfilippo disease type C).</strong> Am. J. Hum. Genet. 79: 738-744, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16960811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16960811</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16960811[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16960811">Fan et al. (2006)</a> performed mutation analyses of 2 MPS IIIC cell lines and identified a splice junction mutation that accounted for 3 mutant alleles and a single-basepair insertion accounting for the fourth. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16960811" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#9" class="mim-tip-reference" title="Hrebicek, M., Mrazova, L., Seyrantepe, V., Durand, S., Roslin, N. M., Noskova, L., Hartmannova, H., Ivanek, R., Cizkova, A., Poupetova, H., Sikora, J., Urinovska, J., and 18 others. <strong>Mutations in TMEM76 cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome).</strong> Am. J. Hum. Genet. 79: 807-819, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033958</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033958[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508294" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17033958">Hrebicek et al. (2006)</a> identified the HGSNAT gene as the site of mutations causing MPS IIIC. Among 30 probands, they found 4 nonsense mutations, 3 frameshift mutations due to deletions or a duplication, 6 splice site mutations, and 14 missense mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17033958" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 unrelated Portuguese patients with MPS IIIC, <a href="#4" class="mim-tip-reference" title="Coutinho, M. F., Lacerda, L., Prata, M. J., Ribeiro, H., Lopes, L., Ferreira, C., Alves, S. <strong>Molecular characterization of Portuguese patients with mucopolysaccharidosis IIIC: two novel mutations in the HGSNAT gene. (Letter)</strong> Clin. Genet. 74: 194-195, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18518886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18518886</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2008.01040.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18518886">Coutinho et al. (2008)</a> identified 2 different mutations in the HGSNAT gene (<a href="#0006">610453.0006</a> and <a href="#0007">610453.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18518886" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#12" class="mim-tip-reference" title="Ruijter, G. J. G., Valstar, M. J., van de Kamp, J. M., van der Helm, R. M., Durand, S., van Diggelen, O. P., Wevers, R. A., Poorthuis, B. J., Pshezhetsky, A. V., Wijburg, F. A. <strong>Clinical and genetic spectrum of Sanfilippo type C (MPS IIIC) disease in The (sic) Netherlands.</strong> Molec. Genet. Metab. 93: 104-111, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18024218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18024218</a>] [<a href="https://doi.org/10.1016/j.ymgme.2007.09.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18024218">Ruijter et al. (2008)</a> reported a high frequency of 2 HGSNAT mutations in the Dutch population (R344C; <a href="#0008">610453.0008</a> and S518F; <a href="#0009">610453.0009</a>), which occurred in 22 and 29.3% of mutant alleles, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18024218" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Feldhammer, M., Durand, S., Mrazova, L., Boucher, R.-M., Laframboise, R., Steinfeld, R., Wraith, J. E., Michelakakis, H., van Diggelen, O. P., Hrebicek, M., Kmoch, S., Pshezhetsky, A. V. <strong>Sanfilippo syndrome type C: mutation spectrum in the heparan sulfate acetyl-CoA: alpha-glucosaminide N-acetyltransferase (HGSNAT) gene.</strong> Hum. Mutat. 30: 918-925, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19479962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19479962</a>] [<a href="https://doi.org/10.1002/humu.20986" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19479962">Feldhammer et al. (2009)</a> stated that 50 pathogenic mutations in the HGSNAT gene had been reported to date, and the authors identified 10 novel mutations. A review of published mutations showed that they span the entire HGSNAT gene, and there were no obvious genotype/phenotype correlations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19479962" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#3" class="mim-tip-reference" title="Canals, I., Elalaoui, S. C., Pineda, M., Delgadillo, V., Szlago, M., Jaouad, I. C., Sefiani, A., Chabas, A., Coll, M. J., Grinberg, D., Vilageliu, L. <strong>Molecular analysis of Sanfilippo syndrome type C in Spain: seven novel HGSNAT mutations and characterization of the mutant alleles.</strong> Clin. Genet. 80: 367-374, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20825431/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20825431</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2010.01525.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20825431">Canals et al. (2011)</a> identified 9 different pathogenic mutations in the HGSNAT gene, including 7 novel mutations, in 11 patients with MPS IIIC, including 7 of Spanish origin, 1 from Argentina, and 3 from Morocco. The most common mutation was 372-2A-G (<a href="#0007">610453.0007</a>), which was found in 4 Spanish patients, with a frequency of 50% (7 of 14 alleles) for the Spanish patients. The second most common mutation was 234+1G-A (<a href="#0010">610453.0010</a>), which was found in 1 Spanish and 2 Moroccan patients. Haplotype analysis indicated a founder effect for both of these mutations. Each of the 7 novel mutations was found in only 1 patient. In vitro functional expression assays in COS-7 cells showed that missense mutations had practically no residual enzyme activity (range, 0-1.19%). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20825431" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Retinitis Pigmentosa 73</em></strong></p><p>
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In 6 affected individuals from 2 Ashkenazi Jewish families and 1 Dutch family with nonsyndromic retinitis pigmentosa (RP73; <a href="/entry/616544">616544</a>), <a href="#8" class="mim-tip-reference" title="Haer-Wigman, L., Newman, H., Leibu, R., Bax, N. M., Baris, H. N., Rizel, L., Banin, E., Massarweh, A., Roosing, S., Lefeber, D. J., Zonneveld-Vrieling, M. N., Isakov, O., Shomron, N., Sharon, D., Den Hollander, A. I., Hoyng, C. B., Cremers, F. P. M., Ben-Yosef, T. <strong>Non-syndromic retinitis pigmentosa due to mutations in the mucopolysaccharidosis type IIIC gene, heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT).</strong> Hum. Molec. Genet. 24: 3742-3751, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25859010/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25859010</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25859010[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddv118" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25859010">Haer-Wigman et al. (2015)</a> identified homozygosity for mutations in the HGSNAT gene (<a href="#0011">610453.0011</a>-<a href="#0013">610453.0013</a>). The mutations segregated with disease and were not found in 211 Ashkenazi Jewish controls. Comprehensive examination of affected individuals from all 3 families revealed no extraocular abnormalities, apart from mild hearing impairment at age 59 years in 1 patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25859010" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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=610453[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<p>In a cell line from a patient with MPS IIIC (MPS3C; <a href="/entry/252930">252930</a>), <a href="#5" class="mim-tip-reference" title="Fan, X., Zhang, H., Zhang, S., Bagshaw, R. D., Tropak, M. B., Callahan, J. W., Mahuran, D. J. <strong>Identification of the gene encoding the enzyme deficient in mucopolysaccharidosis IIIC (Sanfilippo disease type C).</strong> Am. J. Hum. Genet. 79: 738-744, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16960811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16960811</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16960811[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16960811">Fan et al. (2006)</a> identified a homozygous G-to-A substitution in the first nucleotide of intron 4 of the HGSNAT gene, resulting in deletion of exon 4. The data indicated that the patient was homozygous for the splice junction mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16960811" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs483352894 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs483352894;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/rs483352894?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=rs483352894" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs483352894" 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=RCV000001290 OR RCV000662072 OR RCV001390806" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001290, RCV000662072, RCV001390806" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001290...</a>
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<p>In a cell line from a patient with MPS IIIC (<a href="/entry/252930">252930</a>), <a href="#5" class="mim-tip-reference" title="Fan, X., Zhang, H., Zhang, S., Bagshaw, R. D., Tropak, M. B., Callahan, J. W., Mahuran, D. J. <strong>Identification of the gene encoding the enzyme deficient in mucopolysaccharidosis IIIC (Sanfilippo disease type C).</strong> Am. J. Hum. Genet. 79: 738-744, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16960811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16960811</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16960811[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16960811">Fan et al. (2006)</a> identified compound heterozygosity for a splice junction mutation (<a href="#0001">610453.0001</a>) and an insertion of a single G after nucleotide 1344A, resulting in a frameshift after gly448 and the generation of a premature stop codon 21 codons downstream. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16960811" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 MUCOPOLYSACCHARIDOSIS, TYPE IIIC</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> rs121908282 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908282;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/rs121908282?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=rs121908282" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908282" 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=RCV000001291 OR RCV000504894 OR RCV000512873 OR RCV000763184 OR RCV003330379" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001291, RCV000504894, RCV000512873, RCV000763184, RCV003330379" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001291...</a>
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<p>In a patient with MPS IIIC (<a href="/entry/252930">252930</a>) from the United Kingdom, <a href="#9" class="mim-tip-reference" title="Hrebicek, M., Mrazova, L., Seyrantepe, V., Durand, S., Roslin, N. M., Noskova, L., Hartmannova, H., Ivanek, R., Cizkova, A., Poupetova, H., Sikora, J., Urinovska, J., and 18 others. <strong>Mutations in TMEM76 cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome).</strong> Am. J. Hum. Genet. 79: 807-819, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033958</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033958[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508294" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17033958">Hrebicek et al. (2006)</a> identified homozygosity for a 932C-T transition in exon 9 of the HGSNAT gene, resulting in a pro311-to-leu (P311L) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17033958" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 MUCOPOLYSACCHARIDOSIS, TYPE IIIC</strong>
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HGSNAT, LEU349TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908283 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908283;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=rs121908283" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908283" 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=RCV000001292" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001292" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001292</a>
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<p>In a patient with MPS IIIC (<a href="/entry/252930">252930</a>) from the Czech Republic, <a href="#9" class="mim-tip-reference" title="Hrebicek, M., Mrazova, L., Seyrantepe, V., Durand, S., Roslin, N. M., Noskova, L., Hartmannova, H., Ivanek, R., Cizkova, A., Poupetova, H., Sikora, J., Urinovska, J., and 18 others. <strong>Mutations in TMEM76 cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome).</strong> Am. J. Hum. Genet. 79: 807-819, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033958</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033958[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508294" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17033958">Hrebicek et al. (2006)</a> identified compound heterozygosity for mutation in the HGSNAT gene: a 1046T-G transversion in exon 10, resulting in a leu349-to-ter (L349X) substitution, and a 1529T-A transversion in exon 14, resulting in a met510-to-lys (M510K) substitution (<a href="#0005">610453.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17033958" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0005" class="mim-anchor"></a>
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<strong>.0005 MUCOPOLYSACCHARIDOSIS, TYPE IIIC</strong>
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HGSNAT, MET510LYS
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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> rs121908284 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908284;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/rs121908284?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=rs121908284" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908284" 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=RCV000001293 OR RCV001378638 OR RCV003323346 OR RCV004984634" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001293, RCV001378638, RCV003323346, RCV004984634" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001293...</a>
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<p>For discussion of the met510-to-lys (M510K) mutation in the HGSNAT gene that was found in compound heterozygous state in a patient with mucopolysaccharidosis type IIIC (MPS3C; <a href="/entry/252930">252930</a>) by <a href="#9" class="mim-tip-reference" title="Hrebicek, M., Mrazova, L., Seyrantepe, V., Durand, S., Roslin, N. M., Noskova, L., Hartmannova, H., Ivanek, R., Cizkova, A., Poupetova, H., Sikora, J., Urinovska, J., and 18 others. <strong>Mutations in TMEM76 cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome).</strong> Am. J. Hum. Genet. 79: 807-819, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033958</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033958[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508294" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17033958">Hrebicek et al. (2006)</a>, see <a href="#0004">610453.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17033958" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 MUCOPOLYSACCHARIDOSIS, TYPE IIIC</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">rs483352895 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs483352895;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=rs483352895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs483352895" 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=RCV000001294 OR RCV002243612 OR RCV002476908" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001294, RCV002243612, RCV002476908" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001294...</a>
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<p>In 3 unrelated Portuguese patients with MPS IIIC (<a href="/entry/252930">252930</a>), <a href="#4" class="mim-tip-reference" title="Coutinho, M. F., Lacerda, L., Prata, M. J., Ribeiro, H., Lopes, L., Ferreira, C., Alves, S. <strong>Molecular characterization of Portuguese patients with mucopolysaccharidosis IIIC: two novel mutations in the HGSNAT gene. (Letter)</strong> Clin. Genet. 74: 194-195, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18518886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18518886</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2008.01040.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18518886">Coutinho et al. (2008)</a> identified a 1-bp insertion (525dupT) in exon 5 of the HGSNAT gene, resulting in a frameshift and premature protein truncation. Two patients were homozygous for the mutation, and the third was compound heterozygous with a splice site mutation (<a href="#0007">610453.0007</a>), which was predicted to result in nonsense-mediated mRNA decay. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18518886" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0007" class="mim-anchor"></a>
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<strong>.0007 MUCOPOLYSACCHARIDOSIS, TYPE IIIC</strong>
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HGSNAT, IVS3AS, A-G, -2
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs483352896 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs483352896;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/rs483352896?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=rs483352896" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs483352896" 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=RCV000001295 OR RCV000586364 OR RCV001067306" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001295, RCV000586364, RCV001067306" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001295...</a>
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<p>In a Portuguese patient with MPS IIIC (<a href="/entry/252930">252930</a>), <a href="#4" class="mim-tip-reference" title="Coutinho, M. F., Lacerda, L., Prata, M. J., Ribeiro, H., Lopes, L., Ferreira, C., Alves, S. <strong>Molecular characterization of Portuguese patients with mucopolysaccharidosis IIIC: two novel mutations in the HGSNAT gene. (Letter)</strong> Clin. Genet. 74: 194-195, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18518886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18518886</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2008.01040.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18518886">Coutinho et al. (2008)</a> identified compound heterozygosity for an A-to-G transition (372-2A-G) and the 525dupT (<a href="#0006">610453.0006</a>) mutation in the HGSNAT gene. The splice site mutation was predicted to result in the skipping of exon 4 and nonsense-mediated mRNA decay. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18518886" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#3" class="mim-tip-reference" title="Canals, I., Elalaoui, S. C., Pineda, M., Delgadillo, V., Szlago, M., Jaouad, I. C., Sefiani, A., Chabas, A., Coll, M. J., Grinberg, D., Vilageliu, L. <strong>Molecular analysis of Sanfilippo syndrome type C in Spain: seven novel HGSNAT mutations and characterization of the mutant alleles.</strong> Clin. Genet. 80: 367-374, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20825431/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20825431</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2010.01525.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20825431">Canals et al. (2011)</a> identified the 372-2A-G mutation in 4 Spanish patients with MPS IIIC. Three were homozygous for the mutation and 1 was heterozygous. Haplotype analysis indicated a founder effect. Transcript analysis showed that the mutation resulted in 2 transcripts: 1 with skipping of exon 4, creating a frameshift and a premature stop codon, and the other with an in-frame deletion of 4 amino acids. Only 1 of the transcripts was subject to nonsense-mediated mRNA decay. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20825431" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs121908285 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908285;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/rs121908285?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=rs121908285" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908285" 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=RCV000001296 OR RCV000799182 OR RCV001030801 OR RCV001699017 OR RCV003114169 OR RCV003887846" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001296, RCV000799182, RCV001030801, RCV001699017, RCV003114169, RCV003887846" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001296...</a>
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<p><a href="#12" class="mim-tip-reference" title="Ruijter, G. J. G., Valstar, M. J., van de Kamp, J. M., van der Helm, R. M., Durand, S., van Diggelen, O. P., Wevers, R. A., Poorthuis, B. J., Pshezhetsky, A. V., Wijburg, F. A. <strong>Clinical and genetic spectrum of Sanfilippo type C (MPS IIIC) disease in The (sic) Netherlands.</strong> Molec. Genet. Metab. 93: 104-111, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18024218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18024218</a>] [<a href="https://doi.org/10.1016/j.ymgme.2007.09.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18024218">Ruijter et al. (2008)</a> identified a 1030C-T transition in exon 11 of the HGSNAT gene, resulting in an arg344-to-cys (R344C) substitution, in 22% of mutant alleles among 29 patients with MPS IIIC (<a href="/entry/252930">252930</a>). All of the patients were of Dutch origin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18024218" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Feldhammer, M., Durand, S., Mrazova, L., Boucher, R.-M., Laframboise, R., Steinfeld, R., Wraith, J. E., Michelakakis, H., van Diggelen, O. P., Hrebicek, M., Kmoch, S., Pshezhetsky, A. V. <strong>Sanfilippo syndrome type C: mutation spectrum in the heparan sulfate acetyl-CoA: alpha-glucosaminide N-acetyltransferase (HGSNAT) gene.</strong> Hum. Mutat. 30: 918-925, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19479962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19479962</a>] [<a href="https://doi.org/10.1002/humu.20986" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19479962">Feldhammer et al. (2009)</a> identified the R344C mutation in patients from Germany and Singapore. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19479962" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By in vitro functional expression studies in COS-7 cells, <a href="#3" class="mim-tip-reference" title="Canals, I., Elalaoui, S. C., Pineda, M., Delgadillo, V., Szlago, M., Jaouad, I. C., Sefiani, A., Chabas, A., Coll, M. J., Grinberg, D., Vilageliu, L. <strong>Molecular analysis of Sanfilippo syndrome type C in Spain: seven novel HGSNAT mutations and characterization of the mutant alleles.</strong> Clin. Genet. 80: 367-374, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20825431/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20825431</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2010.01525.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20825431">Canals et al. (2011)</a> demonstrated that the mutant R344C protein had almost no residual enzyme activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20825431" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs121908286 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908286;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/rs121908286?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=rs121908286" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908286" 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=RCV000001297 OR RCV001723529 OR RCV001851534" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001297, RCV001723529, RCV001851534" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001297...</a>
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<p><a href="#12" class="mim-tip-reference" title="Ruijter, G. J. G., Valstar, M. J., van de Kamp, J. M., van der Helm, R. M., Durand, S., van Diggelen, O. P., Wevers, R. A., Poorthuis, B. J., Pshezhetsky, A. V., Wijburg, F. A. <strong>Clinical and genetic spectrum of Sanfilippo type C (MPS IIIC) disease in The (sic) Netherlands.</strong> Molec. Genet. Metab. 93: 104-111, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18024218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18024218</a>] [<a href="https://doi.org/10.1016/j.ymgme.2007.09.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18024218">Ruijter et al. (2008)</a> identified a 1553C-T transition in exon 16 of the HGSNAT gene, resulting in a ser518-to-phe (S518F) substitution, in 29.3% of mutant alleles among 29 patients with MPS IIIC (<a href="/entry/252930">252930</a>). The mutation occurred only in patients of Dutch origin, suggesting a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18024218" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Feldhammer, M., Durand, S., Mrazova, L., Boucher, R.-M., Laframboise, R., Steinfeld, R., Wraith, J. E., Michelakakis, H., van Diggelen, O. P., Hrebicek, M., Kmoch, S., Pshezhetsky, A. V. <strong>Sanfilippo syndrome type C: mutation spectrum in the heparan sulfate acetyl-CoA: alpha-glucosaminide N-acetyltransferase (HGSNAT) gene.</strong> Hum. Mutat. 30: 918-925, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19479962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19479962</a>] [<a href="https://doi.org/10.1002/humu.20986" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19479962">Feldhammer et al. (2009)</a> identified the S528F mutation in patients of German origin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19479962" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By in vitro functional expression studies in COS-7 cells, <a href="#3" class="mim-tip-reference" title="Canals, I., Elalaoui, S. C., Pineda, M., Delgadillo, V., Szlago, M., Jaouad, I. C., Sefiani, A., Chabas, A., Coll, M. J., Grinberg, D., Vilageliu, L. <strong>Molecular analysis of Sanfilippo syndrome type C in Spain: seven novel HGSNAT mutations and characterization of the mutant alleles.</strong> Clin. Genet. 80: 367-374, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20825431/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20825431</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2010.01525.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20825431">Canals et al. (2011)</a> demonstrated that the mutant S518F protein had almost no residual enzyme activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20825431" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs483352908 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs483352908;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/rs483352908?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=rs483352908" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs483352908" 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=RCV000023817 OR RCV000153361 OR RCV000652843 OR RCV001074236 OR RCV001192638" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023817, RCV000153361, RCV000652843, RCV001074236, RCV001192638" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023817...</a>
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<p>In a Spanish patient and 2 Moroccan patients with MPS IIIC (<a href="/entry/252930">252930</a>), <a href="#3" class="mim-tip-reference" title="Canals, I., Elalaoui, S. C., Pineda, M., Delgadillo, V., Szlago, M., Jaouad, I. C., Sefiani, A., Chabas, A., Coll, M. J., Grinberg, D., Vilageliu, L. <strong>Molecular analysis of Sanfilippo syndrome type C in Spain: seven novel HGSNAT mutations and characterization of the mutant alleles.</strong> Clin. Genet. 80: 367-374, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20825431/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20825431</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2010.01525.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20825431">Canals et al. (2011)</a> identified a homozygous G-to-A transition in intron 2 (234+1G-A) of the HGSNAT gene. Transcript analysis indicated that the mutation resulted in the skipping of exon 2, but not nonsense-mediated mRNA decay. Haplotype analysis indicated a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20825431" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs754875934 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs754875934;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/rs754875934?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=rs754875934" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs754875934" 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=RCV000190843 OR RCV000675051 OR RCV001003048 OR RCV001049013 OR RCV001075594 OR RCV002272169" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000190843, RCV000675051, RCV001003048, RCV001049013, RCV001075594, RCV002272169" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000190843...</a>
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<p>In 3 affected individuals from 2 consanguineous Israeli families of Ashkenazi Jewish descent with nonsyndromic retinitis pigmentosa (RP73; <a href="/entry/616544">616544</a>), <a href="#8" class="mim-tip-reference" title="Haer-Wigman, L., Newman, H., Leibu, R., Bax, N. M., Baris, H. N., Rizel, L., Banin, E., Massarweh, A., Roosing, S., Lefeber, D. J., Zonneveld-Vrieling, M. N., Isakov, O., Shomron, N., Sharon, D., Den Hollander, A. I., Hoyng, C. B., Cremers, F. P. M., Ben-Yosef, T. <strong>Non-syndromic retinitis pigmentosa due to mutations in the mucopolysaccharidosis type IIIC gene, heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT).</strong> Hum. Molec. Genet. 24: 3742-3751, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25859010/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25859010</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25859010[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddv118" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25859010">Haer-Wigman et al. (2015)</a> identified homozygosity for a c.370A-T transversion (c.370A-T, NM_152419.2) in exon 3 of the HGSNAT gene, resulting in an arg124-to-trp (R124W) substitution at a moderately conserved residue. The mutation segregated with disease in both families and was not found in 211 Ashkenazi Jewish, 250 Israeli, or 5,036 mostly Dutch controls, or in the 1000 Genomes Project, Exome Variant Server, or dbSNP databases. RT-PCR of patient and control leukocytes demonstrated that transcripts lacking exon 3 were only detected in patients, suggesting that the c.370A-T variant causes partial skipping of exon 3 and thus a frameshift, predicted to result in a truncated protein (Cys79ValfsTer20) lacking all transmembrane domains and the C terminus. HGSNAT activity in patient blood leukocytes was less than half that of healthy controls, but was in the upper range of that found in patients with mucopolysaccharidosis type IIIC (<a href="/entry/252930">252930</a>). Comprehensive physical examination for extraocular features was negative except for mild hearing impairment in 1 of the RP patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25859010" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs112029032 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs112029032;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/rs112029032?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=rs112029032" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs112029032" 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=RCV000190844 OR RCV000190845 OR RCV000224674 OR RCV000504631 OR RCV000507277 OR RCV001003049 OR RCV001082167 OR RCV003407694" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000190844, RCV000190845, RCV000224674, RCV000504631, RCV000507277, RCV001003049, RCV001082167, RCV003407694" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000190844...</a>
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<p>In 3 Dutch sibs with nonsyndromic retinitis pigmentosa (RP73; <a href="/entry/616544">616544</a>), in whom general physical examination did not reveal any additional symptoms, <a href="#8" class="mim-tip-reference" title="Haer-Wigman, L., Newman, H., Leibu, R., Bax, N. M., Baris, H. N., Rizel, L., Banin, E., Massarweh, A., Roosing, S., Lefeber, D. J., Zonneveld-Vrieling, M. N., Isakov, O., Shomron, N., Sharon, D., Den Hollander, A. I., Hoyng, C. B., Cremers, F. P. M., Ben-Yosef, T. <strong>Non-syndromic retinitis pigmentosa due to mutations in the mucopolysaccharidosis type IIIC gene, heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT).</strong> Hum. Molec. Genet. 24: 3742-3751, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25859010/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25859010</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25859010[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddv118" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25859010">Haer-Wigman et al. (2015)</a> identified homozygosity for a c.1843G-A transition (c.1843G-A, NM_152419.2) in exon 18 of the HGSNAT gene, resulting in an ala615-to-thr (A615T) substitution, as well as heterozygosity for a c.398G-C transversion in exon 4, resulting in a gly133-to-ala (G133A; <a href="#0011">610453.0011</a>) substitution, both at highly conserved residues. The G133A mutation was not found in 211 Ashkenazi Jewish, 250 Israeli, or 5,036 mostly Dutch controls, or in the 1000 Genomes Project, Exome Variant Server, or dbSNP databases. However, the authors noted that the A615T mutation is a rare variant with a mean allele frequency of 0.59% in the European American population of the Exome Variant Server, and a frequency of 0.56% in an exome variant database of 5,036 primarily Dutch individuals. In addition, A615T had previously been reported in patients with mucopolysaccharidosis type IIIC (MPS3C; <a href="/entry/252930">252930</a>), both times homozygously and in combination with another homozygous variant, W403C (<a href="#0014">610453.0014</a>), by <a href="#9" class="mim-tip-reference" title="Hrebicek, M., Mrazova, L., Seyrantepe, V., Durand, S., Roslin, N. M., Noskova, L., Hartmannova, H., Ivanek, R., Cizkova, A., Poupetova, H., Sikora, J., Urinovska, J., and 18 others. <strong>Mutations in TMEM76 cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome).</strong> Am. J. Hum. Genet. 79: 807-819, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033958</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033958[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508294" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17033958">Hrebicek et al. (2006)</a> and <a href="#7" class="mim-tip-reference" title="Feldhammer, M., Durand, S., Mrazova, L., Boucher, R.-M., Laframboise, R., Steinfeld, R., Wraith, J. E., Michelakakis, H., van Diggelen, O. P., Hrebicek, M., Kmoch, S., Pshezhetsky, A. V. <strong>Sanfilippo syndrome type C: mutation spectrum in the heparan sulfate acetyl-CoA: alpha-glucosaminide N-acetyltransferase (HGSNAT) gene.</strong> Hum. Mutat. 30: 918-925, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19479962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19479962</a>] [<a href="https://doi.org/10.1002/humu.20986" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19479962">Feldhammer et al. (2009)</a>. <a href="#8" class="mim-tip-reference" title="Haer-Wigman, L., Newman, H., Leibu, R., Bax, N. M., Baris, H. N., Rizel, L., Banin, E., Massarweh, A., Roosing, S., Lefeber, D. J., Zonneveld-Vrieling, M. N., Isakov, O., Shomron, N., Sharon, D., Den Hollander, A. I., Hoyng, C. B., Cremers, F. P. M., Ben-Yosef, T. <strong>Non-syndromic retinitis pigmentosa due to mutations in the mucopolysaccharidosis type IIIC gene, heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT).</strong> Hum. Molec. Genet. 24: 3742-3751, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25859010/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25859010</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25859010[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddv118" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25859010">Haer-Wigman et al. (2015)</a> stated that it had been shown that A615T results in moderately reduced HGSNAT activity (50 to 70% of wildtype; <a href="#6" class="mim-tip-reference" title="Fedele, A. O., Hopwood, J. J. <strong>Functional analysis of the HGSNAT gene in patients with mucopolysaccharidosis IIIC (Sanfilippo C syndrome).</strong> Hum. Mutat. 31: E1574-1586, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20583299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20583299</a>] [<a href="https://doi.org/10.1002/humu.21286" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20583299">Fedele and Hopwood, 2010</a>), and suggested that although it was unlikely that the homozygous presence of this variant alone could cause retinal dystrophy, it might act as a modifier in patients with RP due to other genes. HGSNAT activity in blood leukocytes from the 3 Dutch sibs with RP was less than half that of healthy controls, but was slightly higher than that found in patients with MPS3C. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17033958+25859010+20583299+19479962" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By functional analysis of the A615T and W403C mutations that had been found together in homozygosity in patients with MPS3C, <a href="#6" class="mim-tip-reference" title="Fedele, A. O., Hopwood, J. J. <strong>Functional analysis of the HGSNAT gene in patients with mucopolysaccharidosis IIIC (Sanfilippo C syndrome).</strong> Hum. Mutat. 31: E1574-1586, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20583299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20583299</a>] [<a href="https://doi.org/10.1002/humu.21286" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20583299">Fedele and Hopwood (2010)</a> found that the mutations function together to abolish HGSNAT activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20583299" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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">rs797045120 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs797045120;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=rs797045120" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs797045120" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the c.398G-C transversion (c.398G-C, NM_152419.2) in the HGSNAT gene, resulting in a gly122-to-ala (G133A) substitution, that was found in compound heterozygous state in 3 Dutch sibs with retinitis pigmentosa (RP73; <a href="/entry/616544">616544</a>) by <a href="#8" class="mim-tip-reference" title="Haer-Wigman, L., Newman, H., Leibu, R., Bax, N. M., Baris, H. N., Rizel, L., Banin, E., Massarweh, A., Roosing, S., Lefeber, D. J., Zonneveld-Vrieling, M. N., Isakov, O., Shomron, N., Sharon, D., Den Hollander, A. I., Hoyng, C. B., Cremers, F. P. M., Ben-Yosef, T. <strong>Non-syndromic retinitis pigmentosa due to mutations in the mucopolysaccharidosis type IIIC gene, heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT).</strong> Hum. Molec. Genet. 24: 3742-3751, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25859010/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25859010</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25859010[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddv118" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25859010">Haer-Wigman et al. (2015)</a>, see <a href="#0012">610453.0012</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25859010" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 MUCOPOLYSACCHARIDOSIS, TYPE IIIC</strong>
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HGSNAT, TRP403CYS
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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> rs764206492 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs764206492;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/rs764206492?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=rs764206492" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs764206492" 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=RCV000190846 OR RCV002500583 OR RCV003417693" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000190846, RCV002500583, RCV003417693" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000190846...</a>
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<p>For discussion of the homozygous c.1209G-T transversion (c.1209G-T, NM_152419.2) in the HGSNAT gene, resulting in a trp403-to-cys substitution (W403C), that was originally found in compound heterozygous state in patients with mucopolysaccharidosis type IIIC (MPS3C; <a href="/entry/252930">252930</a>) by <a href="#9" class="mim-tip-reference" title="Hrebicek, M., Mrazova, L., Seyrantepe, V., Durand, S., Roslin, N. M., Noskova, L., Hartmannova, H., Ivanek, R., Cizkova, A., Poupetova, H., Sikora, J., Urinovska, J., and 18 others. <strong>Mutations in TMEM76 cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome).</strong> Am. J. Hum. Genet. 79: 807-819, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033958</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033958[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508294" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17033958">Hrebicek et al. (2006)</a>, see <a href="#0012">610453.0012</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17033958" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<br />
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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-font">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<a id="Ausseil2006" class="mim-anchor"></a>
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<strong>An acetylated 120-kDa lysosomal transmembrane protein is absent from mucopolysaccharidosis IIIC fibroblasts: a candidate molecule for MPS IIIC.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16293432/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16293432</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16293432" 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/j.ymgme.2005.09.021" target="_blank">Full Text</a>]
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<a id="Bame1986" class="mim-anchor"></a>
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Bame, K. J., Rome, L. H.
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<strong>Genetic evidence for transmembrane acetylation by lysosomes.</strong>
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Science 233: 1087-1089, 1986.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3090688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3090688</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3090688" 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/10.1126/science.3090688" target="_blank">Full Text</a>]
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<a id="Canals2011" class="mim-anchor"></a>
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Canals, I., Elalaoui, S. C., Pineda, M., Delgadillo, V., Szlago, M., Jaouad, I. C., Sefiani, A., Chabas, A., Coll, M. J., Grinberg, D., Vilageliu, L.
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<strong>Molecular analysis of Sanfilippo syndrome type C in Spain: seven novel HGSNAT mutations and characterization of the mutant alleles.</strong>
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Clin. Genet. 80: 367-374, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20825431/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20825431</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20825431" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2010.01525.x" target="_blank">Full Text</a>]
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<a id="Coutinho2008" class="mim-anchor"></a>
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Coutinho, M. F., Lacerda, L., Prata, M. J., Ribeiro, H., Lopes, L., Ferreira, C., Alves, S.
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<strong>Molecular characterization of Portuguese patients with mucopolysaccharidosis IIIC: two novel mutations in the HGSNAT gene. (Letter)</strong>
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Clin. Genet. 74: 194-195, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18518886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18518886</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18518886" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2008.01040.x" target="_blank">Full Text</a>]
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<a id="Fan2006" class="mim-anchor"></a>
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Fan, X., Zhang, H., Zhang, S., Bagshaw, R. D., Tropak, M. B., Callahan, J. W., Mahuran, D. J.
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<strong>Identification of the gene encoding the enzyme deficient in mucopolysaccharidosis IIIC (Sanfilippo disease type C).</strong>
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Am. J. Hum. Genet. 79: 738-744, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16960811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16960811</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16960811[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16960811" 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/10.1086/508068" target="_blank">Full Text</a>]
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<a id="Fedele2010" class="mim-anchor"></a>
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Fedele, A. O., Hopwood, J. J.
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<strong>Functional analysis of the HGSNAT gene in patients with mucopolysaccharidosis IIIC (Sanfilippo C syndrome).</strong>
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Hum. Mutat. 31: E1574-1586, 2010. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20583299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20583299</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20583299" 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.21286" target="_blank">Full Text</a>]
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<a id="Feldhammer2009" class="mim-anchor"></a>
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Feldhammer, M., Durand, S., Mrazova, L., Boucher, R.-M., Laframboise, R., Steinfeld, R., Wraith, J. E., Michelakakis, H., van Diggelen, O. P., Hrebicek, M., Kmoch, S., Pshezhetsky, A. V.
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<strong>Sanfilippo syndrome type C: mutation spectrum in the heparan sulfate acetyl-CoA: alpha-glucosaminide N-acetyltransferase (HGSNAT) gene.</strong>
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Hum. Mutat. 30: 918-925, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19479962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19479962</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19479962" 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.20986" target="_blank">Full Text</a>]
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<a id="Haer-Wigman2015" class="mim-anchor"></a>
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<div class="">
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Haer-Wigman, L., Newman, H., Leibu, R., Bax, N. M., Baris, H. N., Rizel, L., Banin, E., Massarweh, A., Roosing, S., Lefeber, D. J., Zonneveld-Vrieling, M. N., Isakov, O., Shomron, N., Sharon, D., Den Hollander, A. I., Hoyng, C. B., Cremers, F. P. M., Ben-Yosef, T.
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<strong>Non-syndromic retinitis pigmentosa due to mutations in the mucopolysaccharidosis type IIIC gene, heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT).</strong>
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Hum. Molec. Genet. 24: 3742-3751, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25859010/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25859010</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25859010[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25859010" 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/ddv118" target="_blank">Full Text</a>]
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<a id="Hrebicek2006" class="mim-anchor"></a>
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Hrebicek, M., Mrazova, L., Seyrantepe, V., Durand, S., Roslin, N. M., Noskova, L., Hartmannova, H., Ivanek, R., Cizkova, A., Poupetova, H., Sikora, J., Urinovska, J., and 18 others.
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<strong>Mutations in TMEM76 cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome).</strong>
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Am. J. Hum. Genet. 79: 807-819, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033958</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033958[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17033958" 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/10.1086/508294" target="_blank">Full Text</a>]
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<a id="Klein1978" class="mim-anchor"></a>
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Klein, U., Kresse, H., von Figura, K.
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<strong>Sanfilippo syndrome type C: deficiency of acetyl-CoA: alpha-glucosaminide N-acetyltransferase in skin fibroblasts.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33384</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33384" 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.75.10.5185" target="_blank">Full Text</a>]
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<a id="Meikle1995" class="mim-anchor"></a>
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Meikle, P. J., Whittle, A. M., Hopwood, J. J.
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<strong>Human acetyl-coenzyme A:alpha-glucosaminide N-acetyltransferase: kinetic characterization and mechanistic interpretation.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7755582/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7755582</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7755582" 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/10.1042/bj3080327" target="_blank">Full Text</a>]
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<a id="Ruijter2008" class="mim-anchor"></a>
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Ruijter, G. J. G., Valstar, M. J., van de Kamp, J. M., van der Helm, R. M., Durand, S., van Diggelen, O. P., Wevers, R. A., Poorthuis, B. J., Pshezhetsky, A. V., Wijburg, F. A.
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<strong>Clinical and genetic spectrum of Sanfilippo type C (MPS IIIC) disease in The (sic) Netherlands.</strong>
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Molec. Genet. Metab. 93: 104-111, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18024218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18024218</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18024218" 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/j.ymgme.2007.09.011" target="_blank">Full Text</a>]
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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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Marla J. F. O'Neill - updated : 9/8/2015
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 10/11/2011<br>Cassandra L. Kniffin - updated : 9/8/2009<br>Cassandra L. Kniffin - updated : 8/19/2008<br>Patricia A. Hartz - updated : 10/19/2006<br>Victor A. McKusick - updated : 10/9/2006
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<a id="creationDate" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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<div 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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Victor A. McKusick : 9/28/2006
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 06/13/2022
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<div class="row collapse" id="mimCollapseEditHistory">
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<span class="mim-text-font">
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alopez : 10/05/2016<br>mgross : 05/06/2016<br>carol : 9/8/2015<br>carol : 9/8/2015<br>mcolton : 7/10/2015<br>carol : 2/19/2014<br>carol : 2/12/2014<br>mcolton : 2/12/2014<br>carol : 10/13/2011<br>terry : 10/12/2011<br>ckniffin : 10/11/2011<br>wwang : 9/21/2009<br>ckniffin : 9/8/2009<br>wwang : 8/26/2008<br>ckniffin : 8/19/2008<br>terry : 8/9/2007<br>alopez : 10/19/2006<br>carol : 10/10/2006<br>alopez : 10/10/2006<br>carol : 10/9/2006<br>alopez : 9/28/2006
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<h3>
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<span class="mim-font">
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<strong>*</strong> 610453
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</h3>
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<div>
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<h3>
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<span class="mim-font">
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HEPARAN-ALPHA-GLUCOSAMINIDE N-ACETYLTRANSFERASE; HGSNAT
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</h3>
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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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TRANSMEMBRANE PROTEIN 76; TMEM76
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: HGSNAT</em></strong>
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</span>
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</p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 75238000;
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<strong>ICD10CM:</strong> E76.22;
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<strong>
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<em>
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Cytogenetic location: 8p11.21-p11.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 8:43,140,464-43,202,855 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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Location
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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<td rowspan="2">
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<span class="mim-font">
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8p11.21-p11.1
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</span>
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<td>
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<span class="mim-font">
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Mucopolysaccharidosis type IIIC (Sanfilippo C)
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<td>
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<span class="mim-font">
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252930
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<span class="mim-font">
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Autosomal recessive
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</span>
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<td>
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<span class="mim-font">
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3
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<span class="mim-font">
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Retinitis pigmentosa 73
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<td>
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<span class="mim-font">
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616544
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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<td>
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<span class="mim-font">
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3
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The HGSNAT gene encodes heparan acetyl-CoA:alpha-glucosaminide N-acetyltransferase (EC 2.3.1.78), an enzyme that catalyzes acetylation of the terminal glucosamine residues of heparan sulfate prior to its hydrolysis by alpha-N-acetyl glucosaminidase (summary by Klein et al., 1978). The enzyme is sometimes referred to as N-acetyltransferase (Fan et al., 2006). </p>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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<span class="mim-text-font">
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<p>Fan et al. (2006) identified the gene encoding heparan acetyl-CoA:alpha-glucosaminide N-acetyltransferase, the enzyme defective in mucopolysaccharidosis IIIC, also known as Sanfilippo syndrome type C (252930) (Klein et al., 1978). In a proteomics study of mouse lysosomal membrane proteins, Fan et al. (2006) identified an unknown protein whose human homolog, TMEM76, was encoded by a gene that maps to 8p11.1. They expressed a full-length mouse expressed sequence tag (EST) in human MPS IIIC fibroblasts and observed that its protein product localized to the lysosome and corrected the enzymatic defect. Fan et al. (2006) used the mouse sequence to identify the full-length human homolog, HGSNAT. The deduced C-terminal portion of HGSNAT is highly conserved across species, including plants and bacteria; however, the N-terminal portion, extending to transmembrane domain B, is found only in metazoans. Neither of these regions has homology with functional domains identified elsewhere, including those from proteins known to bind CoA or acetyl-CoA; therefore, HGSNAT represents the human member of a new family of enzymes. </p><p>By examining candidate genes in the region of chromosome 8 associated with MPS IIIC, Hrebicek et al. (2006) identified HGSNAT, which they called TMEM76. The deduced 656-amino acid protein with a calculated molecular mass of 73 kD contains an N-terminal signal peptide, 4 putative N-glycosylation sites, and 11 transmembrane domains. Topology modeling predicted the N terminus to be inside the lysosome and the C terminus to be cytosolic. Hrebicek et al. (2006) also identified a splice variant lacking exons 9 and 10 that encodes a protein with an in-frame deletion of 64 amino acids in transmembrane domains 3 and 4. This variant was considered likely to encode an inactive enzyme since it was detected in the RNA of 3 MPS IIIC patients with nearly complete loss of N-acetyltransferase activity. Northern blot analysis detected ubiquitous expression of 4.5- and 2.1-kb transcripts. Highest expression was in leukocytes, heart, lung, placenta, and liver, and much lower expression was found in thymus, colon, and brain. RT-PCR detected TMEM76 in normal human skin, fibroblasts, white blood cells, and skeletal muscle. </p><p>Haer-Wigman et al. (2015) performed RT-PCR analysis of HGSNAT RNA derived from normal human retina and leukocytes. Both tissues yielded the expected product, but the authors noted that obtaining a product from leukocytes required an additional set of amplification, indicating that HGSNAT expression levels in the retina are much higher than those in blood leukocytes. RT-PCR analysis of total RNA from mouse eye showed Hgsnat expression as early as embryonic day 14, with equally high expression levels after birth, at postnatal days 0 and 30. </p>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>N-acetyltransferase is a lysosomal membrane enzyme whose function is to acetylate the nonreducing, terminal alpha-glucosamine residue of intralysosomal heparin or heparan sulfate, converting it into a substrate for luminal alpha-N-acetylglucosaminidase (Fan et al., 2006). Therefore, N-acetyltransferase catalyzes the only synthetic reaction known to occur in the lysosome. To do this, the enzyme uses a cytosolic cofactor, acetyl-coenzyme A (acetyl-CoA). Thus, its substrate and cofactor are separated by the lysosomal membrane. The mechanism by which this spatial problem is overcome is controversial. One model suggests a ping-pong mechanism involving an initial acetylation reaction of the enzyme in the cytosol, followed by a transfer of the acetyl group to the intralysosomal heparin-alpha-glucosamine residue (Bame and Rome, 1986; Ausseil et al., 2006). An alternative model proposes that the enzyme operates via a random order ternary complex mechanism; that is, there is no acetylated enzyme intermediate (Meikle et al., 1995). The enzyme, which proved difficult to purify, is believed to be a dimer of 120 kD subunits containing asn-linked oligosaccharides. It is also postulated that the 120-kD subunit may be only the catalytic subunit of a protein complex whose other unidentified members are also required for functionality. </p><p>Hrebicek et al. (2006) performed functional expression of human HGSNAT and the mouse ortholog and demonstrated that it is the gene that encodes the lysosomal N-acetyltransferase. HGSNAT did not show structural similarity to any known prokaryotic or eukaryotic N-acetyltransferase or to other lysosomal proteins, on the basis of sequence homology searches. The authors suggested that this enzyme belongs to a new structural class of proteins that transport the activated acetyl residues across the cell membrane. </p>
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</span>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Fan et al. (2006) demonstrated that the HGSNAT gene contains 18 exons. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Fan et al. (2006) identified the HGSNAT gene on chromosome 8p11.1 by comparison of mouse and human sequences. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Mucopolysaccharidosis IIIC</em></strong></p><p>
|
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Mucopolysaccharidosis IIIC (MPS3C), or Sanfilippo syndrome type C (252930), is an autosomal recessive disorder characterized by the lysosomal storage of heparin and heparan sulfate. The hallmark of the Sanfilippo syndrome is severe central nervous system involvement but only mild somatic disease. Fan et al. (2006) performed mutation analyses of 2 MPS IIIC cell lines and identified a splice junction mutation that accounted for 3 mutant alleles and a single-basepair insertion accounting for the fourth. </p><p>Hrebicek et al. (2006) identified the HGSNAT gene as the site of mutations causing MPS IIIC. Among 30 probands, they found 4 nonsense mutations, 3 frameshift mutations due to deletions or a duplication, 6 splice site mutations, and 14 missense mutations. </p><p>In 3 unrelated Portuguese patients with MPS IIIC, Coutinho et al. (2008) identified 2 different mutations in the HGSNAT gene (610453.0006 and 610453.0007). </p><p>Ruijter et al. (2008) reported a high frequency of 2 HGSNAT mutations in the Dutch population (R344C; 610453.0008 and S518F; 610453.0009), which occurred in 22 and 29.3% of mutant alleles, respectively. </p><p>Feldhammer et al. (2009) stated that 50 pathogenic mutations in the HGSNAT gene had been reported to date, and the authors identified 10 novel mutations. A review of published mutations showed that they span the entire HGSNAT gene, and there were no obvious genotype/phenotype correlations. </p><p>Canals et al. (2011) identified 9 different pathogenic mutations in the HGSNAT gene, including 7 novel mutations, in 11 patients with MPS IIIC, including 7 of Spanish origin, 1 from Argentina, and 3 from Morocco. The most common mutation was 372-2A-G (610453.0007), which was found in 4 Spanish patients, with a frequency of 50% (7 of 14 alleles) for the Spanish patients. The second most common mutation was 234+1G-A (610453.0010), which was found in 1 Spanish and 2 Moroccan patients. Haplotype analysis indicated a founder effect for both of these mutations. Each of the 7 novel mutations was found in only 1 patient. In vitro functional expression assays in COS-7 cells showed that missense mutations had practically no residual enzyme activity (range, 0-1.19%). </p><p><strong><em>Retinitis Pigmentosa 73</em></strong></p><p>
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In 6 affected individuals from 2 Ashkenazi Jewish families and 1 Dutch family with nonsyndromic retinitis pigmentosa (RP73; 616544), Haer-Wigman et al. (2015) identified homozygosity for mutations in the HGSNAT gene (610453.0011-610453.0013). The mutations segregated with disease and were not found in 211 Ashkenazi Jewish controls. Comprehensive examination of affected individuals from all 3 families revealed no extraocular abnormalities, apart from mild hearing impairment at age 59 years in 1 patient. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>14 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 MUCOPOLYSACCHARIDOSIS, TYPE IIIC</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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HGSNAT, IVS4, G-A, +1
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<br />
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SNP: rs193066451,
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gnomAD: rs193066451,
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ClinVar: RCV000001289, RCV000763183, RCV000780343, RCV002512639
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a cell line from a patient with MPS IIIC (MPS3C; 252930), Fan et al. (2006) identified a homozygous G-to-A substitution in the first nucleotide of intron 4 of the HGSNAT gene, resulting in deletion of exon 4. The data indicated that the patient was homozygous for the splice junction 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>.0002 MUCOPOLYSACCHARIDOSIS, TYPE IIIC</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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HGSNAT, 1-BP INS, 1345G
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<br />
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SNP: rs483352894,
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gnomAD: rs483352894,
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ClinVar: RCV000001290, RCV000662072, RCV001390806
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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 cell line from a patient with MPS IIIC (252930), Fan et al. (2006) identified compound heterozygosity for a splice junction mutation (610453.0001) and an insertion of a single G after nucleotide 1344A, resulting in a frameshift after gly448 and the generation of a premature stop codon 21 codons downstream. </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>.0003 MUCOPOLYSACCHARIDOSIS, TYPE IIIC</strong>
|
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</span>
|
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</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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|
HGSNAT, PRO311LEU
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<br />
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SNP: rs121908282,
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gnomAD: rs121908282,
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ClinVar: RCV000001291, RCV000504894, RCV000512873, RCV000763184, RCV003330379
|
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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 MPS IIIC (252930) from the United Kingdom, Hrebicek et al. (2006) identified homozygosity for a 932C-T transition in exon 9 of the HGSNAT gene, resulting in a pro311-to-leu (P311L) substitution. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
|
|
</div>
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|
</div>
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|
<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 MUCOPOLYSACCHARIDOSIS, TYPE IIIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
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|
|
HGSNAT, LEU349TER
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<br />
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|
|
SNP: rs121908283,
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|
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ClinVar: RCV000001292
|
|
|
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|
|
</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with MPS IIIC (252930) from the Czech Republic, Hrebicek et al. (2006) identified compound heterozygosity for mutation in the HGSNAT gene: a 1046T-G transversion in exon 10, resulting in a leu349-to-ter (L349X) substitution, and a 1529T-A transversion in exon 14, resulting in a met510-to-lys (M510K) substitution (610453.0005). </p>
|
|
</span>
|
|
</div>
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|
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<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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|
|
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 MUCOPOLYSACCHARIDOSIS, TYPE IIIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
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|
|
|
HGSNAT, MET510LYS
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<br />
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|
|
SNP: rs121908284,
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|
|
gnomAD: rs121908284,
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|
|
ClinVar: RCV000001293, RCV001378638, RCV003323346, RCV004984634
|
|
|
|
|
|
</span>
|
|
</div>
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|
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the met510-to-lys (M510K) mutation in the HGSNAT gene that was found in compound heterozygous state in a patient with mucopolysaccharidosis type IIIC (MPS3C; 252930) by Hrebicek et al. (2006), see 610453.0004. </p>
|
|
</span>
|
|
</div>
|
|
|
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|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 MUCOPOLYSACCHARIDOSIS, TYPE IIIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HGSNAT, 1-BP INS, 525T
|
|
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|
|
<br />
|
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|
|
SNP: rs483352895,
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|
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|
|
|
|
|
ClinVar: RCV000001294, RCV002243612, RCV002476908
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 unrelated Portuguese patients with MPS IIIC (252930), Coutinho et al. (2008) identified a 1-bp insertion (525dupT) in exon 5 of the HGSNAT gene, resulting in a frameshift and premature protein truncation. Two patients were homozygous for the mutation, and the third was compound heterozygous with a splice site mutation (610453.0007), which was predicted to result in nonsense-mediated mRNA decay. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MUCOPOLYSACCHARIDOSIS, TYPE IIIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HGSNAT, IVS3AS, A-G, -2
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs483352896,
|
|
|
|
|
|
gnomAD: rs483352896,
|
|
|
|
|
|
ClinVar: RCV000001295, RCV000586364, RCV001067306
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Portuguese patient with MPS IIIC (252930), Coutinho et al. (2008) identified compound heterozygosity for an A-to-G transition (372-2A-G) and the 525dupT (610453.0006) mutation in the HGSNAT gene. The splice site mutation was predicted to result in the skipping of exon 4 and nonsense-mediated mRNA decay. </p><p>Canals et al. (2011) identified the 372-2A-G mutation in 4 Spanish patients with MPS IIIC. Three were homozygous for the mutation and 1 was heterozygous. Haplotype analysis indicated a founder effect. Transcript analysis showed that the mutation resulted in 2 transcripts: 1 with skipping of exon 4, creating a frameshift and a premature stop codon, and the other with an in-frame deletion of 4 amino acids. Only 1 of the transcripts was subject to nonsense-mediated mRNA decay. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 MUCOPOLYSACCHARIDOSIS, TYPE IIIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HGSNAT, ARG344CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908285,
|
|
|
|
|
|
gnomAD: rs121908285,
|
|
|
|
|
|
ClinVar: RCV000001296, RCV000799182, RCV001030801, RCV001699017, RCV003114169, RCV003887846
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Ruijter et al. (2008) identified a 1030C-T transition in exon 11 of the HGSNAT gene, resulting in an arg344-to-cys (R344C) substitution, in 22% of mutant alleles among 29 patients with MPS IIIC (252930). All of the patients were of Dutch origin. </p><p>Feldhammer et al. (2009) identified the R344C mutation in patients from Germany and Singapore. </p><p>By in vitro functional expression studies in COS-7 cells, Canals et al. (2011) demonstrated that the mutant R344C protein had almost no residual enzyme activity. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 MUCOPOLYSACCHARIDOSIS, TYPE IIIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HGSNAT, SER518PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908286,
|
|
|
|
|
|
gnomAD: rs121908286,
|
|
|
|
|
|
ClinVar: RCV000001297, RCV001723529, RCV001851534
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Ruijter et al. (2008) identified a 1553C-T transition in exon 16 of the HGSNAT gene, resulting in a ser518-to-phe (S518F) substitution, in 29.3% of mutant alleles among 29 patients with MPS IIIC (252930). The mutation occurred only in patients of Dutch origin, suggesting a founder effect. </p><p>Feldhammer et al. (2009) identified the S528F mutation in patients of German origin. </p><p>By in vitro functional expression studies in COS-7 cells, Canals et al. (2011) demonstrated that the mutant S518F protein had almost no residual enzyme activity. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MUCOPOLYSACCHARIDOSIS, TYPE IIIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HGSNAT, IVS2DS, G-A, +1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs483352908,
|
|
|
|
|
|
gnomAD: rs483352908,
|
|
|
|
|
|
ClinVar: RCV000023817, RCV000153361, RCV000652843, RCV001074236, RCV001192638
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Spanish patient and 2 Moroccan patients with MPS IIIC (252930), Canals et al. (2011) identified a homozygous G-to-A transition in intron 2 (234+1G-A) of the HGSNAT gene. Transcript analysis indicated that the mutation resulted in the skipping of exon 2, but not nonsense-mediated mRNA decay. Haplotype analysis indicated a founder effect. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 RETINITIS PIGMENTOSA 73</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HGSNAT, ARG124TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs754875934,
|
|
|
|
|
|
gnomAD: rs754875934,
|
|
|
|
|
|
ClinVar: RCV000190843, RCV000675051, RCV001003048, RCV001049013, RCV001075594, RCV002272169
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 affected individuals from 2 consanguineous Israeli families of Ashkenazi Jewish descent with nonsyndromic retinitis pigmentosa (RP73; 616544), Haer-Wigman et al. (2015) identified homozygosity for a c.370A-T transversion (c.370A-T, NM_152419.2) in exon 3 of the HGSNAT gene, resulting in an arg124-to-trp (R124W) substitution at a moderately conserved residue. The mutation segregated with disease in both families and was not found in 211 Ashkenazi Jewish, 250 Israeli, or 5,036 mostly Dutch controls, or in the 1000 Genomes Project, Exome Variant Server, or dbSNP databases. RT-PCR of patient and control leukocytes demonstrated that transcripts lacking exon 3 were only detected in patients, suggesting that the c.370A-T variant causes partial skipping of exon 3 and thus a frameshift, predicted to result in a truncated protein (Cys79ValfsTer20) lacking all transmembrane domains and the C terminus. HGSNAT activity in patient blood leukocytes was less than half that of healthy controls, but was in the upper range of that found in patients with mucopolysaccharidosis type IIIC (252930). Comprehensive physical examination for extraocular features was negative except for mild hearing impairment in 1 of the RP patients. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 RETINITIS PIGMENTOSA 73</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
MUCOPOLYSACCHARIDOSIS, TYPE IIIC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HGSNAT, ALA615THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs112029032,
|
|
|
|
|
|
gnomAD: rs112029032,
|
|
|
|
|
|
ClinVar: RCV000190844, RCV000190845, RCV000224674, RCV000504631, RCV000507277, RCV001003049, RCV001082167, RCV003407694
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 Dutch sibs with nonsyndromic retinitis pigmentosa (RP73; 616544), in whom general physical examination did not reveal any additional symptoms, Haer-Wigman et al. (2015) identified homozygosity for a c.1843G-A transition (c.1843G-A, NM_152419.2) in exon 18 of the HGSNAT gene, resulting in an ala615-to-thr (A615T) substitution, as well as heterozygosity for a c.398G-C transversion in exon 4, resulting in a gly133-to-ala (G133A; 610453.0011) substitution, both at highly conserved residues. The G133A mutation was not found in 211 Ashkenazi Jewish, 250 Israeli, or 5,036 mostly Dutch controls, or in the 1000 Genomes Project, Exome Variant Server, or dbSNP databases. However, the authors noted that the A615T mutation is a rare variant with a mean allele frequency of 0.59% in the European American population of the Exome Variant Server, and a frequency of 0.56% in an exome variant database of 5,036 primarily Dutch individuals. In addition, A615T had previously been reported in patients with mucopolysaccharidosis type IIIC (MPS3C; 252930), both times homozygously and in combination with another homozygous variant, W403C (610453.0014), by Hrebicek et al. (2006) and Feldhammer et al. (2009). Haer-Wigman et al. (2015) stated that it had been shown that A615T results in moderately reduced HGSNAT activity (50 to 70% of wildtype; Fedele and Hopwood, 2010), and suggested that although it was unlikely that the homozygous presence of this variant alone could cause retinal dystrophy, it might act as a modifier in patients with RP due to other genes. HGSNAT activity in blood leukocytes from the 3 Dutch sibs with RP was less than half that of healthy controls, but was slightly higher than that found in patients with MPS3C. </p><p>By functional analysis of the A615T and W403C mutations that had been found together in homozygosity in patients with MPS3C, Fedele and Hopwood (2010) found that the mutations function together to abolish HGSNAT activity. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 RETINITIS PIGMENTOSA 73</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HGSNAT, GLY133ALA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs797045120,
|
|
|
|
|
|
|
|
ClinVar: RCV000190842
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.398G-C transversion (c.398G-C, NM_152419.2) in the HGSNAT gene, resulting in a gly122-to-ala (G133A) substitution, that was found in compound heterozygous state in 3 Dutch sibs with retinitis pigmentosa (RP73; 616544) by Haer-Wigman et al. (2015), see 610453.0012. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
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<span class="mim-font">
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<strong>.0014 MUCOPOLYSACCHARIDOSIS, TYPE IIIC</strong>
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</h4>
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<span class="mim-text-font">
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HGSNAT, TRP403CYS
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<br />
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SNP: rs764206492,
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gnomAD: rs764206492,
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ClinVar: RCV000190846, RCV002500583, RCV003417693
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<span class="mim-text-font">
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<p>For discussion of the homozygous c.1209G-T transversion (c.1209G-T, NM_152419.2) in the HGSNAT gene, resulting in a trp403-to-cys substitution (W403C), that was originally found in compound heterozygous state in patients with mucopolysaccharidosis type IIIC (MPS3C; 252930) by Hrebicek et al. (2006), see 610453.0012. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<p />
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</div>
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<ol>
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<li>
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<p class="mim-text-font">
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Ausseil, J., Landry, K., Seyrantepe, V., Trudel, S., Mazur, A., Lapointe, F., Pshezhetsky, A. V.
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<strong>An acetylated 120-kDa lysosomal transmembrane protein is absent from mucopolysaccharidosis IIIC fibroblasts: a candidate molecule for MPS IIIC.</strong>
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Molec. Genet. Metab. 87: 22-31, 2006.
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[PubMed: 16293432]
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[Full Text: https://doi.org/10.1016/j.ymgme.2005.09.021]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Bame, K. J., Rome, L. H.
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<strong>Genetic evidence for transmembrane acetylation by lysosomes.</strong>
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Science 233: 1087-1089, 1986.
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[PubMed: 3090688]
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[Full Text: https://doi.org/10.1126/science.3090688]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Canals, I., Elalaoui, S. C., Pineda, M., Delgadillo, V., Szlago, M., Jaouad, I. C., Sefiani, A., Chabas, A., Coll, M. J., Grinberg, D., Vilageliu, L.
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<strong>Molecular analysis of Sanfilippo syndrome type C in Spain: seven novel HGSNAT mutations and characterization of the mutant alleles.</strong>
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Clin. Genet. 80: 367-374, 2011.
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[PubMed: 20825431]
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[Full Text: https://doi.org/10.1111/j.1399-0004.2010.01525.x]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Coutinho, M. F., Lacerda, L., Prata, M. J., Ribeiro, H., Lopes, L., Ferreira, C., Alves, S.
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<strong>Molecular characterization of Portuguese patients with mucopolysaccharidosis IIIC: two novel mutations in the HGSNAT gene. (Letter)</strong>
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Clin. Genet. 74: 194-195, 2008.
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[PubMed: 18518886]
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[Full Text: https://doi.org/10.1111/j.1399-0004.2008.01040.x]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Fan, X., Zhang, H., Zhang, S., Bagshaw, R. D., Tropak, M. B., Callahan, J. W., Mahuran, D. J.
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<strong>Identification of the gene encoding the enzyme deficient in mucopolysaccharidosis IIIC (Sanfilippo disease type C).</strong>
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Am. J. Hum. Genet. 79: 738-744, 2006.
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[PubMed: 16960811]
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[Full Text: https://doi.org/10.1086/508068]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Fedele, A. O., Hopwood, J. J.
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<strong>Functional analysis of the HGSNAT gene in patients with mucopolysaccharidosis IIIC (Sanfilippo C syndrome).</strong>
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Hum. Mutat. 31: E1574-1586, 2010. Note: Electronic Article.
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[PubMed: 20583299]
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[Full Text: https://doi.org/10.1002/humu.21286]
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</li>
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<li>
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<p class="mim-text-font">
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Feldhammer, M., Durand, S., Mrazova, L., Boucher, R.-M., Laframboise, R., Steinfeld, R., Wraith, J. E., Michelakakis, H., van Diggelen, O. P., Hrebicek, M., Kmoch, S., Pshezhetsky, A. V.
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<strong>Sanfilippo syndrome type C: mutation spectrum in the heparan sulfate acetyl-CoA: alpha-glucosaminide N-acetyltransferase (HGSNAT) gene.</strong>
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Hum. Mutat. 30: 918-925, 2009.
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[PubMed: 19479962]
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[Full Text: https://doi.org/10.1002/humu.20986]
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</li>
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<li>
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<p class="mim-text-font">
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Haer-Wigman, L., Newman, H., Leibu, R., Bax, N. M., Baris, H. N., Rizel, L., Banin, E., Massarweh, A., Roosing, S., Lefeber, D. J., Zonneveld-Vrieling, M. N., Isakov, O., Shomron, N., Sharon, D., Den Hollander, A. I., Hoyng, C. B., Cremers, F. P. M., Ben-Yosef, T.
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<strong>Non-syndromic retinitis pigmentosa due to mutations in the mucopolysaccharidosis type IIIC gene, heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT).</strong>
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Hum. Molec. Genet. 24: 3742-3751, 2015.
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[PubMed: 25859010]
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[Full Text: https://doi.org/10.1093/hmg/ddv118]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Hrebicek, M., Mrazova, L., Seyrantepe, V., Durand, S., Roslin, N. M., Noskova, L., Hartmannova, H., Ivanek, R., Cizkova, A., Poupetova, H., Sikora, J., Urinovska, J., and 18 others.
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<strong>Mutations in TMEM76 cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome).</strong>
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Am. J. Hum. Genet. 79: 807-819, 2006.
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[PubMed: 17033958]
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[Full Text: https://doi.org/10.1086/508294]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Klein, U., Kresse, H., von Figura, K.
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<strong>Sanfilippo syndrome type C: deficiency of acetyl-CoA: alpha-glucosaminide N-acetyltransferase in skin fibroblasts.</strong>
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Proc. Nat. Acad. Sci. 75: 5185-5189, 1978.
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[PubMed: 33384]
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[Full Text: https://doi.org/10.1073/pnas.75.10.5185]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Meikle, P. J., Whittle, A. M., Hopwood, J. J.
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<strong>Human acetyl-coenzyme A:alpha-glucosaminide N-acetyltransferase: kinetic characterization and mechanistic interpretation.</strong>
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Biochem. J. 308: 327-333, 1995.
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[PubMed: 7755582]
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[Full Text: https://doi.org/10.1042/bj3080327]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Ruijter, G. J. G., Valstar, M. J., van de Kamp, J. M., van der Helm, R. M., Durand, S., van Diggelen, O. P., Wevers, R. A., Poorthuis, B. J., Pshezhetsky, A. V., Wijburg, F. A.
|
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<strong>Clinical and genetic spectrum of Sanfilippo type C (MPS IIIC) disease in The (sic) Netherlands.</strong>
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Molec. Genet. Metab. 93: 104-111, 2008.
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[PubMed: 18024218]
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[Full Text: https://doi.org/10.1016/j.ymgme.2007.09.011]
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</p>
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</li>
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</ol>
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<div>
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<br />
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</div>
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Marla J. F. O'Neill - updated : 9/8/2015<br>Cassandra L. Kniffin - updated : 10/11/2011<br>Cassandra L. Kniffin - updated : 9/8/2009<br>Cassandra L. Kniffin - updated : 8/19/2008<br>Patricia A. Hartz - updated : 10/19/2006<br>Victor A. McKusick - updated : 10/9/2006
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Victor A. McKusick : 9/28/2006
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