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Entry
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- *609701 - N-ACETYLGLUCOSAMINIDASE, ALPHA-; NAGLU
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- OMIM
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<p>
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<span class="h4">*609701</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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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#animalModel">Animal Model</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/609701">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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<li role="presentation">
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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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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<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 id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="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=ENSG00000108784;t=ENST00000225927" 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=4669" 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=609701" 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="small">
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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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<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=ENSG00000108784;t=ENST00000225927" 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_000263,XM_017024687,XM_024450771,XM_047436138,XM_047436139" 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_000263" 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=609701" 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=02017&isoform_id=02017_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/NAGLU" 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/1171229,1171231,1197840,1479981,1479983,32450702,66346698,119581236,119581237,317373322,332367478,1034599876,1240148481,1240148483,1240148485,1370471090,2217312124,2217312127,2462555527,2462555529,2462555531,2462555533" 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/P54802" 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=4669" 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=ENSG00000108784;t=ENST00000225927" 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=NAGLU" 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=NAGLU" 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+4669" 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/NAGLU" 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:4669" 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/4669" 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=chr17&hgg_gene=ENST00000585572.1&hgg_start=42536241&hgg_end=42544449&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/genes/HGNC:7632" 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/naglu" 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=609701[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=609701[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000108784" 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=NAGLU" 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=NAGLU" 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=NAGLU" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=NAGLU&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/PA31437" 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:7632" 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/FBgn0014417.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:1351641" 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/NAGLU#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:1351641" 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/4669/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA001342/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=4669" 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://wormbase.org/db/gene/gene?name=WBGene00010722;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-100726-2" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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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:4669" 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=NAGLU&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> 1187618009, 59990008<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>
|
|
609701
|
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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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N-ACETYLGLUCOSAMINIDASE, ALPHA-; NAGLU
|
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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>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
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<p>
|
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<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
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</p>
|
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</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
N-ACETYL-ALPHA-D-GLUCOSAMINIDASE<br />
|
|
N-ACETYL-ALPHA-GLUCOSAMINIDASE
|
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</span>
|
|
</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>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=NAGLU" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">NAGLU</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/17/579?start=-3&limit=10&highlight=579">17q21.2</a>
|
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr17:42536241-42544449&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'})">17:42,536,241-42,544,449</a> </span>
|
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</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=616491,252920" 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/17/579?start=-3&limit=10&highlight=579">
|
|
17q21.2
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
?Charcot-Marie-Tooth disease, axonal, type 2V
|
|
|
|
<span class="mim-tip-hint" title="A question mark (?) indicates that the relationship between the phenotype and gene is provisional">
|
|
<span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span>
|
|
</span>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/616491"> 616491 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</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>
|
|
</td>
|
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</tr>
|
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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Mucopolysaccharidosis type IIIB (Sanfilippo B)
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/252920"> 252920 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
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<p><a href="#21" class="mim-tip-reference" title="Zhao, H. G., Li, H. H., Schmidtchen, A., Bach, G., Neufeld, E. F. <strong>The gene encoding alpha-N-acetylglucosaminidase and mutations underlying Sanfilippo B syndrome. (Abstract)</strong> Am. J. Hum. Genet. 57: A185 only, 1995."None>Zhao et al. (1995)</a> and <a href="#20" class="mim-tip-reference" title="Zhao, H. G., Li, H. H., Bach, G., Schmidtchen, A., Neufeld, E. F. <strong>The molecular basis of Sanfilippo syndrome type B.</strong> Proc. Nat. Acad. Sci. 93: 6101-6105, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8650226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8650226</a>] [<a href="https://doi.org/10.1073/pnas.93.12.6101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8650226">Zhao et al. (1996)</a> cloned a cDNA corresponding to alpha-N-acetylglucosaminidase, which they symbolized NAGLU. The deduced 743-amino acid protein has a 20- to 23-residue leader sequence, consistent with a signal peptide, and 6 potential N-glycosylation sites. The mature protein contains 720 amino acids and has a molecular mass of approximately 80 kD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8650226" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Weber, B., Blanch, L., Clements, P. R., Scott, H. S., Hopwood, J. J. <strong>Cloning and expression of the gene involved in Sanfilippo B syndrome (mucopolysaccharidosis IIIB).</strong> Hum. Molec. Genet. 5: 771-777, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8776591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8776591</a>] [<a href="https://doi.org/10.1093/hmg/5.6.771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8776591">Weber et al. (1996)</a> reported the cloning of the NAGLU gene by enzyme protein purification, amino acid sequence determination, and database searches. A TFASTA search aligned the amino acid sequence to sequence in the 5-prime flanking region of the 17-beta-hydroxysteroid dehydrogenase-1 gene (HSD17B1; <a href="/entry/109684">109684</a>), and this sequence was used to screen cDNA libraries. Northern blot analysis showed a single 2.7-kb mRNA transcript with high expression levels in liver, ovary, and peripheral blood leukocytes and measurable amounts of transcript in other tissues. The full-length cDNA sequence was cloned into an expression vector, and cultured CHO cells transfected with this vector showed a 17-fold increase in enzyme expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8776591" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="#20" class="mim-tip-reference" title="Zhao, H. G., Li, H. H., Bach, G., Schmidtchen, A., Neufeld, E. F. <strong>The molecular basis of Sanfilippo syndrome type B.</strong> Proc. Nat. Acad. Sci. 93: 6101-6105, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8650226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8650226</a>] [<a href="https://doi.org/10.1073/pnas.93.12.6101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8650226">Zhao et al. (1996)</a> determined that the NAGLU gene contains 6 exons and spans 8.3 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8650226" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="#20" class="mim-tip-reference" title="Zhao, H. G., Li, H. H., Bach, G., Schmidtchen, A., Neufeld, E. F. <strong>The molecular basis of Sanfilippo syndrome type B.</strong> Proc. Nat. Acad. Sci. 93: 6101-6105, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8650226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8650226</a>] [<a href="https://doi.org/10.1073/pnas.93.12.6101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8650226">Zhao et al. (1996)</a> mapped the NAGLU gene to chromosome 17q21. The 3-prime end of NAGLU resides in the upstream flanking region of the HSD17B1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8650226" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="#14" class="mim-tip-reference" title="Vance, J. M., Pericak-Vance, M. A., Elston, R. C., Conneally, P. M., Namboodiri, K. K., Wappner, R. S., Yu, P. L. <strong>Evidence of genetic variation for alpha-N-acetyl-D-glucosaminidase in black and white populations: a new polymorphism.</strong> Am. J. Med. Genet. 7: 131-140, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6781343/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6781343</a>] [<a href="https://doi.org/10.1002/ajmg.1320070207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6781343">Vance et al. (1980)</a> demonstrated variable alpha-N-acetylglucosaminidase activity levels among different groups of normal control populations, indicating polymorphisms within the gene that encodes the enzyme. <a href="#8" class="mim-tip-reference" title="Pericak-Vance, M. A., Vance, J. M., Elston, R. C., Namboodiri, K. K., Fogle, T. A. <strong>Segregation and linkage analysis of alpha-N-acetyl-D-glucosaminidase (NAG) levels in a black family.</strong> Am. J. Med. Genet. 20: 295-306, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3976723/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3976723</a>] [<a href="https://doi.org/10.1002/ajmg.1320200213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3976723">Pericak-Vance et al. (1985)</a> confirmed the polymorphisms reported by <a href="#14" class="mim-tip-reference" title="Vance, J. M., Pericak-Vance, M. A., Elston, R. C., Conneally, P. M., Namboodiri, K. K., Wappner, R. S., Yu, P. L. <strong>Evidence of genetic variation for alpha-N-acetyl-D-glucosaminidase in black and white populations: a new polymorphism.</strong> Am. J. Med. Genet. 7: 131-140, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6781343/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6781343</a>] [<a href="https://doi.org/10.1002/ajmg.1320070207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6781343">Vance et al. (1980)</a> in studies of a large black kindred. They pointed out that alleles for high and low NAG enzyme activity might confuse the identification of heterozygotes. The mean values for NAG activity of the 3 genotypes varied in black and in white groups. Thermal stability data were cited suggesting that structurally distinct allelic forms of the enzyme may be segregating in the 2 racial groups. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3976723+6781343" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Mucopolysaccharidosis, Type IIIB</em></strong></p><p>
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Using SSCP analysis of PCR-amplified segments of genomic DNA from patients with Sanfilippo syndrome B, also known as mucopolysaccharidosis IIIB (MPS3B; <a href="/entry/252920">252920</a>), <a href="#20" class="mim-tip-reference" title="Zhao, H. G., Li, H. H., Bach, G., Schmidtchen, A., Neufeld, E. F. <strong>The molecular basis of Sanfilippo syndrome type B.</strong> Proc. Nat. Acad. Sci. 93: 6101-6105, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8650226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8650226</a>] [<a href="https://doi.org/10.1073/pnas.93.12.6101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8650226">Zhao et al. (1996)</a> identified several recessive mutations in the NAGLU gene (see, e.g., <a href="#0001">609701.0001</a>-<a href="#0005">609701.0005</a>). All missense mutations occurred at CpG sites, known to be mutagenic hotspots. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8650226" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Zhao, H. G., Aronovich, E. L., Whitley, C. B. <strong>Genotype-phenotype correspondence in Sanfilippo syndrome type B.</strong> Am. J. Hum. Genet. 62: 53-63, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9443875/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9443875</a>] [<a href="https://doi.org/10.1086/301682" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9443875">Zhao et al. (1998)</a> stated that 36% of all known point mutations in the NAGLU gene causing MPS IIIB (8 of 22 alleles) involve arginine-674 (see, e.g., <a href="#0001">609701.0001</a>), a codon having a CpG dinucleotide in the critical initial position. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9443875" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 9 fibroblast cell lines of Sanfilippo syndrome B patients, <a href="#10" class="mim-tip-reference" title="Schmidtchen, A., Greenberg, D., Zhao, H. G., Li, H. H., Huang, Y., Tieu, P., Zhao, H.-Z., Cheng, S., Zhao, Z., Whitley, C. B., Di Natale, P., Neufeld, E. F. <strong>NAGLU mutations underlying Sanfilippo syndrome type B.</strong> Am. J. Hum. Genet. 62: 64-69, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9443878/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9443878</a>] [<a href="https://doi.org/10.1086/301685" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9443878">Schmidtchen et al. (1998)</a> identified 10 additional mutations in the NAGLU gene. Functional expression studies showed that the mutant enzymes had no residual activity. Nine of the 10 amino acid substitutions that had been identified to that time clustered near the amino or the carboxy end of the enzyme, suggesting a role for these regions in the transport or function of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9443878" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#1" class="mim-tip-reference" title="Beesley, C. E., Young, E. P., Vellodi, A., Winchester, B. G. <strong>Identification of 12 novel mutations in the alpha-N-acetylglucosaminidase gene in 14 patients with Sanfilippo syndrome type B (mucopolysaccharidosis type IIIB).</strong> J. Med. Genet. 35: 910-914, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9832037/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9832037</a>] [<a href="https://doi.org/10.1136/jmg.35.11.910" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9832037">Beesley et al. (1998)</a> identified 12 novel mutations in the NAGLU gene in 14 patients with MPS IIIB. <a href="#2" class="mim-tip-reference" title="Bunge, S., Knigge, A., Steglich, C., Kleijer, W. J., van Diggelen, O. P., Beck, M., Gal, A. <strong>Mucopolysaccharidosis type IIIB (Sanfilippo B): identification of 18 novel alpha-N-acetylglucosaminidase gene mutations.</strong> J. Med. Genet. 36: 28-31, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9950362/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9950362</a>]" pmid="9950362">Bunge et al. (1999)</a> identified 21 mutations, including 18 novel mutations, in the NAGLU gene in 22 patients with MPS IIIB. The mutation spectrum consisted of 2 small insertions, 2 small deletions, 3 nonsense mutations, and 14 different missense mutations, 1 of which affected the initiation codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9832037+9950362" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a study of 40 patients with Sanfilippo syndrome B, most of them of Australasian and Dutch origin, <a href="#16" class="mim-tip-reference" title="Weber, B., Guo, X.-H., Kleijer, W. J., van de Kamp, J. J. P., Poorthuis, B. J. H. M., Hopwood, J. J. <strong>Sanfilippo type B syndrome (mucopolysaccharidosis III B): allelic heterogeneity corresponds to the wide spectrum of clinical phenotypes.</strong> Europ. J. Hum. Genet. 7: 34-44, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10094189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10094189</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10094189">Weber et al. (1999)</a> identified 31 mutations, 25 of them novel, and 2 polymorphisms in the NAGLU gene. The observed allelic heterogeneity reflected the wide spectrum of clinical phenotypes reported for these patients. Most of the changes were missense mutations; 4 nonsense and 9 frameshift mutations caused by insertions or deletions were also identified. Only 5 mutations were found in more than 1 patient. R643C (<a href="#0006">609701.0006</a>) and R297X (<a href="#0003">609701.0003</a>) each accounted for approximately 20% of MPS IIIB alleles in the Dutch patient group, while R297X, P521L (<a href="#0007">609701.0007</a>), R565W (<a href="#0008">609701.0008</a>), and R626X (<a href="#0002">609701.0002</a>) each had a frequency of about 6% in Australasian patients. R643C seemed to be a Dutch MPS IIIB allele and clearly conferred an attenuated phenotype. One region of the gene showed a higher concentration of mutations, probably reflecting the instability of this area which contains a direct repeat. Several arginine residues seemed to be hotspots for mutations, being affected by 2 or 3 individual basepair exchanges (see <a href="#0004">609701.0004</a> and <a href="#0006">609701.0006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10094189" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a mutation screen of 20 patients with Sanfilippo syndrome B, <a href="#12" class="mim-tip-reference" title="Tessitore, A., Villani, G. R. D., Di Domenico, C., Filocamo, M., Gatti, R., Di Natale, P. <strong>Molecular defects in the alpha-N-acetylglucosaminidase gene in Italian Sanfilippo type B patients.</strong> Hum. Genet. 107: 568-576, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11153910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11153910</a>] [<a href="https://doi.org/10.1007/s004390000429" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11153910">Tessitore et al. (2000)</a> identified 28 mutations, 14 of which were novel, in the NAGLU gene. Of these mutations, 4 were found in homozygosity and only 1 was seen in 2 different patients, showing the remarkable molecular heterogeneity of the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11153910" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#17" class="mim-tip-reference" title="Yogalingam, G., Hopwood, J. J. <strong>Molecular genetics of mucopolysaccharidosis type IIIA and IIIB: diagnostic, clinical, and biological implications.</strong> Hum. Mutat. 18: 264-281, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11668611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11668611</a>] [<a href="https://doi.org/10.1002/humu.1189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11668611">Yogalingam and Hopwood (2001)</a> reported that 86 new mutations had been identified in the NAGLU gene in MPS IIIB patients: 58 missense/nonsense mutations, 27 insertion/deletions, and 1 splice site mutation. All mutations were associated with severe clinical phenotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11668611" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Tanaka, A., Kimura, M., Lan, H. T. N., Takaura, N., Yamano, T. <strong>Molecular analysis of the alpha-N-acetylglucosaminidase gene in seven Japanese patients from six unrelated families with mucopolysaccharidosis IIIB (Sanfilippo type B), including two novel mutations.</strong> J. Hum. Genet. 47: 484-487, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12202988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12202988</a>] [<a href="https://doi.org/10.1007/s100380200070" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12202988">Tanaka et al. (2002)</a> performed molecular analysis of the NAGLU gene in 7 Japanese patients with Sanfilippo syndrome type B from 6 unrelated families; 6 disease-causing mutations were found, of which 2 were novel. Two families were from Okinawa, where more patients with Sanfilippo syndrome were found than in other areas in Japan. Two sibs, who were compound heterozygous for F314L (<a href="#0011">609701.0011</a>) and R565P (<a href="#0009">609701.0009</a>), showed an attenuated form. Two patients with a severe phenotype with rapid progression were homozygous for R482W (<a href="#0012">609701.0012</a>) and R565P, respectively. <a href="#11" class="mim-tip-reference" title="Tanaka, A., Kimura, M., Lan, H. T. N., Takaura, N., Yamano, T. <strong>Molecular analysis of the alpha-N-acetylglucosaminidase gene in seven Japanese patients from six unrelated families with mucopolysaccharidosis IIIB (Sanfilippo type B), including two novel mutations.</strong> J. Hum. Genet. 47: 484-487, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12202988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12202988</a>] [<a href="https://doi.org/10.1007/s100380200070" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12202988">Tanaka et al. (2002)</a> suggested that the R565P mutation is common in Okinawa. <a href="#3" class="mim-tip-reference" title="Chinen, Y., Tohma, T., Izumikawa, Y., Uehara, H., Ohta, T. <strong>Sanfilippo type B syndrome: five patients with an R565P homozygous mutation in the alpha-N-acetylglucosaminidase gene from the Okinawa islands in Japan.</strong> J. Hum. Genet. 50: 357-359, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15933803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15933803</a>] [<a href="https://doi.org/10.1007/s10038-005-0258-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15933803">Chinen et al. (2005)</a> identified the homozygous R565P mutation in 5 unrelated Japanese patients from Okinawa, suggesting a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12202988+15933803" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Najmabadi, H., Hu, H., Garshasbi, M., Zemojtel, T., Abedini, S. S., Chen, W., Hosseini, M., Behjati, F., Haas, S., Jamali, P., Zecha, A., Mohseni, M., and 33 others. <strong>Deep sequencing reveals 50 novel genes for recessive cognitive disorders.</strong> Nature 478: 57-63, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21937992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21937992</a>] [<a href="https://doi.org/10.1038/nature10423" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21937992">Najmabadi et al. (2011)</a> performed homozygosity mapping followed by exon enrichment and next-generation sequencing in 136 consanguineous families (over 90% Iranian and less than 10% Turkish or Arab) segregating syndromic or nonsyndromic forms of autosomal recessive intellectual disability. They identified a family (8600486) in which 3 of 4 children, born to parents related as first cousins once removed, had MPS IIIB (severe intellectual disability, autism spectrum disorder, and coarse facial features) and a homozygous missense mutation in the NAGLU gene (<a href="#0014">609701.0014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21937992" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Charcot-Marie-Tooth Disease, Axonal, Type 2V</em></strong></p><p>
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In affected members of a large French Canadian kindred with autosomal dominant axonal Charcot-Marie-Tooth disease type 2V (CMT2V; <a href="/entry/616491">616491</a>), <a href="#13" class="mim-tip-reference" title="Tetreault, M., Gonzalez, M., Dicaire, M.-J., Allard, P., Gehring, K., Leblanc, D., Leclerc, N., Schondorf, R., Mathieu, J., Zuchner, S., Brais, B. <strong>Adult-onset painful axonal polyneuropathy caused by a dominant NAGLU mutation.</strong> Brain 138: 1477-1483, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25818867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25818867</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25818867[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/brain/awv074" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25818867">Tetreault et al. (2015)</a> identified a heterozygous missense mutation in the NAGLU gene (I403T; <a href="#0015">609701.0015</a>). The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family. Patient leukocytes showed significantly decreased NAGLU enzyme activity (36-54% of controls), consistent with a detrimental effect of the mutation. The patients had adult onset of progressive lower leg pain and distal sensory impairment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25818867" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In the study of <a href="#16" class="mim-tip-reference" title="Weber, B., Guo, X.-H., Kleijer, W. J., van de Kamp, J. J. P., Poorthuis, B. J. H. M., Hopwood, J. J. <strong>Sanfilippo type B syndrome (mucopolysaccharidosis III B): allelic heterogeneity corresponds to the wide spectrum of clinical phenotypes.</strong> Europ. J. Hum. Genet. 7: 34-44, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10094189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10094189</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10094189">Weber et al. (1999)</a>, all mutations resulting in premature termination either by a nonsense mutation or frameshift insertions and deletions led to the severe phenotype. Similarly, deletions masking the normal stop codon and presumably elongating the gene product conferred a severe phenotype when in combination with R297X. Missense mutations V334F and P521L also caused the severe phenotype when present on both alleles in individual patients. Most of the Dutch patients showed clinical symptoms consistent with the attenuated form of the disease. Two patients were diagnosed at the age of 63 and 47 years, respectively. Two of the attenuated cases, who were apparently not related, were found to be homozygous for R643C, an allele that was also identified in an attenuated patient with an unknown second allele. Two patients with R297X in combination with an unknown genotype (compound heterozygotes) had the severe and attenuated phenotype, respectively, implying that the unknown alleles modified the severity of the clinical phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10094189" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="#4" class="mim-tip-reference" title="Li, H. H., Yu, W.-H., Rozengurt, N., Zhao, H.-Z., Lyons, K. M., Anagnostaras, S., Fanselow, M. S., Suzuki, K., Vanier, M. T., Neufeld, E. F. <strong>Mouse model of Sanfilippo syndrome type B produced by targeted disruption of the gene encoding alpha-N-acetylglucosaminidase.</strong> Proc. Nat. Acad. Sci. 96: 14505-14510, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10588735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10588735</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10588735[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.25.14505" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10588735">Li et al. (1999)</a> found that Naglu-deficient mice were healthy and fertile while young and could survive for 8 to 12 months. They were totally deficient in alpha-N-acetylglucosaminidase and had massive accumulation of heparan sulfate in liver and kidney, as well as secondary changes in activity of several other lysosomal enzymes in liver and brain and elevation of gangliosides GM2 and GM3 in brain. Vacuolation was seen in many cells, including macrophages, epithelial cells, and neurons, and became more prominent with age. Although most vacuoles contained finely granular material characteristic of glycosaminoglycan accumulation, large pleiomorphic inclusions were seen in some neurons and pericytes in the brain. Abnormal hypoactive behavior was manifested by 4.5-month-old Naglu -/- mice in an open field test; the hyperactivity that is characteristic of affected children was not observed even in younger mice. In a pavlovian fear conditioning test, the 4.5-month-old mutant mice showed normal response to context, indicating intact hippocampal-dependent learning, but reduced response to a conditioning tone, perhaps attributable to hearing impairment. The phenotype of the deficient mice was considered sufficiently similar to that of patients with Sanfilippo syndrome B to make these mice a good model for study of pathophysiology and for development of therapy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10588735" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 mouse models, <a href="#7" class="mim-tip-reference" title="Ohmi, K., Greenberg, D. S., Rajavel, K. S., Ryazantsev, S., Li, H. H., Neufeld, E. F. <strong>Activated microglia in cortex of mouse models of mucopolysaccharidoses I and IIIB.</strong> Proc. Nat. Acad. Sci. 100: 1902-1907, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12576554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12576554</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12576554[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.252784899" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12576554">Ohmi et al. (2003)</a> investigated the implications of microglial involvement for the pathogenesis as well as the potential treatment of MPS I (see <a href="/entry/607014">607014</a>) and MPS IIIB. Their investigation showed an inflammatory component of brain disease in both disorders, as is known for many neurodegenerative disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12576554" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Ryazantsev, S., Yu, W.-H., Zhao, H.-Z., Neufeld, E. F., Ohmi, K. <strong>Lysosomal accumulation of SCMAS (subunit c of mitochondrial ATP synthase) in neurons of the mouse model of mucopolysaccharidosis III B.</strong> Molec. Genet. Metab. 90: 393-401, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17185018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17185018</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17185018[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ymgme.2006.11.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17185018">Ryazantsev et al. (2007)</a> performed a detailed study of the brain pathology in mice deficient for the Naglu gene developed by <a href="#4" class="mim-tip-reference" title="Li, H. H., Yu, W.-H., Rozengurt, N., Zhao, H.-Z., Lyons, K. M., Anagnostaras, S., Fanselow, M. S., Suzuki, K., Vanier, M. T., Neufeld, E. F. <strong>Mouse model of Sanfilippo syndrome type B produced by targeted disruption of the gene encoding alpha-N-acetylglucosaminidase.</strong> Proc. Nat. Acad. Sci. 96: 14505-14510, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10588735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10588735</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10588735[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.25.14505" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10588735">Li et al. (1999)</a>. In contrast to somatic cells, which accumulate primarily heparan sulfate, neurons accumulate a number of apparently unrelated metabolites, including subunit c of mitochondrial ATPase synthase (SCMAS). SCMAS accumulated from 1 month of age, primarily in the medial entorhinal cortex and layer V of the somatosensory cortex. Its accumulation was not due to the absence of specific proteases. Light microscopy of brain sections of 6-month-old mice showed SCMAS to accumulate in the same organelles as Lamp1 (<a href="/entry/153330">153330</a>) and Lamp2 (<a href="/entry/309060">309060</a>). Cryoimmunoelectron microscopy showed SCMAS to be present in Lamp-positive vesicles bounded by a single membrane (lysosomes), in fingerprint-like layered arrays. GM3 ganglioside was also seen in lysosomes of microglia, suggesting phagocytosis of neuronal membranes. Samples used for cryoelectron microscopy and further processed by standard electron microscopy procedures showed the disappearance of the SCMAS fingerprint arrays and appearance in the same location of 'zebra bodies,' well known but little understood inclusions in the brain of patients with mucopolysaccharidosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10588735+17185018" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs104894590 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894590;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/rs104894590?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=rs104894590" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894590" 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=RCV000001626 OR RCV000078455 OR RCV000817080" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001626, RCV000078455, RCV000817080" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001626...</a>
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<p>In 2 Arab patients with Sanfilippo B syndrome, or mucopolysaccharidosis type IIIB (MPS3B; <a href="/entry/252920">252920</a>), <a href="#20" class="mim-tip-reference" title="Zhao, H. G., Li, H. H., Bach, G., Schmidtchen, A., Neufeld, E. F. <strong>The molecular basis of Sanfilippo syndrome type B.</strong> Proc. Nat. Acad. Sci. 93: 6101-6105, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8650226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8650226</a>] [<a href="https://doi.org/10.1073/pnas.93.12.6101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8650226">Zhao et al. (1996)</a> identified a homozygous 2021G-A transition in the NAGLU gene, resulting in an arg674-to-his (R674H) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8650226" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs104894591 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894591;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/rs104894591?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=rs104894591" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894591" 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=RCV000001627 OR RCV000153533 OR RCV000802847" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001627, RCV000153533, RCV000802847" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001627...</a>
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<p>In a cell line (GM156) from a patient with Sanfilippo syndrome B (MPS3B; <a href="/entry/252920">252920</a>) from the Human Genetic Mutant Cell Repository, <a href="#20" class="mim-tip-reference" title="Zhao, H. G., Li, H. H., Bach, G., Schmidtchen, A., Neufeld, E. F. <strong>The molecular basis of Sanfilippo syndrome type B.</strong> Proc. Nat. Acad. Sci. 93: 6101-6105, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8650226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8650226</a>] [<a href="https://doi.org/10.1073/pnas.93.12.6101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8650226">Zhao et al. (1996)</a> identified a homozygous 1876C-T transition in the NAGLU gene, resulting in an arg626-to-ter (R626X) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8650226" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 IIIB</strong>
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NAGLU, ARG297TER
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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> rs104894592 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894592;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/rs104894592?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=rs104894592" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894592" 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=RCV000001628 OR RCV000485168 OR RCV001030805 OR RCV001041784" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001628, RCV000485168, RCV001030805, RCV001041784" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001628...</a>
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<p>In a cell line (GM156) from a patient with Sanfilippo syndrome B (MPS3B; <a href="/entry/252920">252920</a>) from the Human Genetic Mutant Cell Repository, <a href="#20" class="mim-tip-reference" title="Zhao, H. G., Li, H. H., Bach, G., Schmidtchen, A., Neufeld, E. F. <strong>The molecular basis of Sanfilippo syndrome type B.</strong> Proc. Nat. Acad. Sci. 93: 6101-6105, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8650226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8650226</a>] [<a href="https://doi.org/10.1073/pnas.93.12.6101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8650226">Zhao et al. (1996)</a> identified compound heterozygosity for 2 mutations in the NAGLU gene: an 889C-T transition, resulting in an arg297-to-ter (R297X) substitution, and a G-to-A transition, resulting in an arg643-to-his (R643H; <a href="#0004">609701.0004</a>) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8650226" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Weber, B., Guo, X.-H., Kleijer, W. J., van de Kamp, J. J. P., Poorthuis, B. J. H. M., Hopwood, J. J. <strong>Sanfilippo type B syndrome (mucopolysaccharidosis III B): allelic heterogeneity corresponds to the wide spectrum of clinical phenotypes.</strong> Europ. J. Hum. Genet. 7: 34-44, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10094189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10094189</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10094189">Weber et al. (1999)</a> found that the R297X mutation was the most common mutation in a cohort of Dutch and Australasian MPS IIIB patients, occurring at a frequency of 12.5%. <a href="#18" class="mim-tip-reference" title="Yogalingam, G., Weber, B., Meehan, J., Rogers, J., Hopwood, J. J. <strong>Mucopolysaccharidosis type IIIB: characterisation and expression of wild-type and mutant recombinant alpha-N-acetylglucosaminidase and relationship with Sanfilippo phenotype in an attenuated patient.</strong> Biochim. Biophys. Acta 1502: 415-425, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11068184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11068184</a>] [<a href="https://doi.org/10.1016/s0925-4439(00)00066-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11068184">Yogalingam et al. (2000)</a> found that this mutation was associated with very low levels of NAGLU activity and 12-fold elevations of 35-S-labeled GAG storage when compared with normal fibroblasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10094189+11068184" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 IIIB</strong>
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NAGLU, ARG643HIS
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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> rs104894593 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894593;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/rs104894593?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=rs104894593" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894593" 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=RCV000001629 OR RCV001227283" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001629, RCV001227283" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001629...</a>
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<p>For discussion of the arg643-to-his (R643H) mutation in the NAGLU gene that was found in compound heterozygous state in a cell line (GM156) from a patient with Sanfilippo syndrome B (MPS3B; <a href="/entry/252920">252920</a>) by <a href="#20" class="mim-tip-reference" title="Zhao, H. G., Li, H. H., Bach, G., Schmidtchen, A., Neufeld, E. F. <strong>The molecular basis of Sanfilippo syndrome type B.</strong> Proc. Nat. Acad. Sci. 93: 6101-6105, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8650226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8650226</a>] [<a href="https://doi.org/10.1073/pnas.93.12.6101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8650226">Zhao et al. (1996)</a>, see <a href="#0003">609701.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8650226" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Weber, B., Guo, X.-H., Kleijer, W. J., van de Kamp, J. J. P., Poorthuis, B. J. H. M., Hopwood, J. J. <strong>Sanfilippo type B syndrome (mucopolysaccharidosis III B): allelic heterogeneity corresponds to the wide spectrum of clinical phenotypes.</strong> Europ. J. Hum. Genet. 7: 34-44, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10094189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10094189</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10094189">Weber et al. (1999)</a> reported that an R643C mutation (<a href="#0006">609701.0006</a>) accounted for approximately 20% of MPS3B alleles in a Dutch patient group, suggesting that this arginine residue is a hotspot for mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10094189" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0005 MUCOPOLYSACCHARIDOSIS, TYPE IIIB</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> rs483352897 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs483352897;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/rs483352897?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=rs483352897" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs483352897" 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=RCV000001630 OR RCV000626637 OR RCV001047802 OR RCV001588794" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001630, RCV000626637, RCV001047802, RCV001588794" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001630...</a>
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<p>In cell line from a patient with Sanfilippo syndrome B (MPS3B; <a href="/entry/252920">252920</a>), <a href="#20" class="mim-tip-reference" title="Zhao, H. G., Li, H. H., Bach, G., Schmidtchen, A., Neufeld, E. F. <strong>The molecular basis of Sanfilippo syndrome type B.</strong> Proc. Nat. Acad. Sci. 93: 6101-6105, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8650226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8650226</a>] [<a href="https://doi.org/10.1073/pnas.93.12.6101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8650226">Zhao et al. (1996)</a> found homozygosity for a 10-bp deletion in the NAGLU gene beginning at nucleotide 503; the deletion resulted in a frameshift and predicted termination 14 codons later. The deletion occurs at a direct repeat of a tetranucleotide, GGAG, and may be the result of slipped mispairing during DNA replication. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8650226" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 IIIB</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> rs104894594 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894594;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/rs104894594?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=rs104894594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894594" 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=RCV000001631 OR RCV001030808 OR RCV001214750 OR RCV001579503" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001631, RCV001030808, RCV001214750, RCV001579503" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001631...</a>
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<p><a href="#16" class="mim-tip-reference" title="Weber, B., Guo, X.-H., Kleijer, W. J., van de Kamp, J. J. P., Poorthuis, B. J. H. M., Hopwood, J. J. <strong>Sanfilippo type B syndrome (mucopolysaccharidosis III B): allelic heterogeneity corresponds to the wide spectrum of clinical phenotypes.</strong> Europ. J. Hum. Genet. 7: 34-44, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10094189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10094189</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10094189">Weber et al. (1999)</a> reported that an arg643-to-cys (R643C) missense mutation in the NAGLU gene accounted for approximately 20% of mucopolysaccharidosis type IIIB (MPS3B; <a href="/entry/252920">252920</a>) alleles in a Dutch patient group. Arginine-643 appears to be a hotspot for mutations; see R643H (<a href="#0004">609701.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10094189" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs104894595 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894595;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/rs104894595?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=rs104894595" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894595" 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=RCV000001632 OR RCV001030807 OR RCV001043674 OR RCV001729332" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001632, RCV001030807, RCV001043674, RCV001729332" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001632...</a>
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<p><a href="#16" class="mim-tip-reference" title="Weber, B., Guo, X.-H., Kleijer, W. J., van de Kamp, J. J. P., Poorthuis, B. J. H. M., Hopwood, J. J. <strong>Sanfilippo type B syndrome (mucopolysaccharidosis III B): allelic heterogeneity corresponds to the wide spectrum of clinical phenotypes.</strong> Europ. J. Hum. Genet. 7: 34-44, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10094189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10094189</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10094189">Weber et al. (1999)</a> found that a pro521-to-leu (P521L) missense mutation in the NAGLU gene accounted for approximately 6% of mutations in Australasian patients with Sanfilippo syndrome B (MPS3B; <a href="/entry/252920">252920</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10094189" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs104894597 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894597;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/rs104894597?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=rs104894597" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894597" 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=RCV000001633 OR RCV001223228 OR RCV002269255" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001633, RCV001223228, RCV002269255" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001633...</a>
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<p><a href="#16" class="mim-tip-reference" title="Weber, B., Guo, X.-H., Kleijer, W. J., van de Kamp, J. J. P., Poorthuis, B. J. H. M., Hopwood, J. J. <strong>Sanfilippo type B syndrome (mucopolysaccharidosis III B): allelic heterogeneity corresponds to the wide spectrum of clinical phenotypes.</strong> Europ. J. Hum. Genet. 7: 34-44, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10094189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10094189</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10094189">Weber et al. (1999)</a> found that an arg565-to-trp (R565W) missense mutation accounted for approximately 6% of the mutant alleles in Australasian patients with Sanfilippo syndrome B (MPS3B; <a href="/entry/252920">252920</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10094189" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0009 MUCOPOLYSACCHARIDOSIS, TYPE IIIB</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> rs104894598 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894598;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/rs104894598?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=rs104894598" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894598" 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=RCV000001634 OR RCV001851558" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001634, RCV001851558" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001634...</a>
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<p><a href="#16" class="mim-tip-reference" title="Weber, B., Guo, X.-H., Kleijer, W. J., van de Kamp, J. J. P., Poorthuis, B. J. H. M., Hopwood, J. J. <strong>Sanfilippo type B syndrome (mucopolysaccharidosis III B): allelic heterogeneity corresponds to the wide spectrum of clinical phenotypes.</strong> Europ. J. Hum. Genet. 7: 34-44, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10094189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10094189</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10094189">Weber et al. (1999)</a> observed an arg565-to-pro (R565P) mutation of the NAGLU gene in compound heterozygous state in a patient with Sanfilippo syndrome B (MPS3B; <a href="/entry/252920">252920</a>). The arginine-565 residue appears to be a hotspot for mutations; see <a href="#0008">609701.0008</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10094189" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Tanaka, A., Kimura, M., Lan, H. T. N., Takaura, N., Yamano, T. <strong>Molecular analysis of the alpha-N-acetylglucosaminidase gene in seven Japanese patients from six unrelated families with mucopolysaccharidosis IIIB (Sanfilippo type B), including two novel mutations.</strong> J. Hum. Genet. 47: 484-487, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12202988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12202988</a>] [<a href="https://doi.org/10.1007/s100380200070" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12202988">Tanaka et al. (2002)</a> identified the R565P mutation in homozygous state in a patient with a severe form of Sanfilippo syndrome B. <a href="#11" class="mim-tip-reference" title="Tanaka, A., Kimura, M., Lan, H. T. N., Takaura, N., Yamano, T. <strong>Molecular analysis of the alpha-N-acetylglucosaminidase gene in seven Japanese patients from six unrelated families with mucopolysaccharidosis IIIB (Sanfilippo type B), including two novel mutations.</strong> J. Hum. Genet. 47: 484-487, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12202988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12202988</a>] [<a href="https://doi.org/10.1007/s100380200070" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12202988">Tanaka et al. (2002)</a> suggested that the R565P mutation may be common in Okinawa. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12202988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Chinen, Y., Tohma, T., Izumikawa, Y., Uehara, H., Ohta, T. <strong>Sanfilippo type B syndrome: five patients with an R565P homozygous mutation in the alpha-N-acetylglucosaminidase gene from the Okinawa islands in Japan.</strong> J. Hum. Genet. 50: 357-359, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15933803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15933803</a>] [<a href="https://doi.org/10.1007/s10038-005-0258-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15933803">Chinen et al. (2005)</a> identified the homozygous R565P mutation in 5 unrelated Japanese patients with Sanfilippo syndrome B, suggesting a founder effect. One of 200 control individuals was heterozygous for the mutation. The R565P substitution results from an 8839G-C transversion in exon 6 of the NAGLU gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15933803" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs104894599 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894599;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/rs104894599?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=rs104894599" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894599" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs118204024 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204024;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs118204024" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs118204024" 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=RCV000001635 OR RCV002512655" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001635, RCV002512655" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001635...</a>
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<p><a href="#18" class="mim-tip-reference" title="Yogalingam, G., Weber, B., Meehan, J., Rogers, J., Hopwood, J. J. <strong>Mucopolysaccharidosis type IIIB: characterisation and expression of wild-type and mutant recombinant alpha-N-acetylglucosaminidase and relationship with Sanfilippo phenotype in an attenuated patient.</strong> Biochim. Biophys. Acta 1502: 415-425, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11068184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11068184</a>] [<a href="https://doi.org/10.1016/s0925-4439(00)00066-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11068184">Yogalingam et al. (2000)</a> reported a patient with an attenuated form of Sanfilippo syndrome B (MPS3B; <a href="/entry/252920">252920</a>) who was a compound heterozygote for 2 mutations in the NAGLU gene: an R297X substitution (<a href="#0003">609701.0003</a>) and a phe48-to-leu (F48L) substitution. The F48L mutation was associated with a partially degraded polypeptide in a 16-hour chase experiment, suggesting that this missense mutation affects the processing and stability of NAGLU. It was associated with significant residual NAGLU activity sufficient to metabolize 34% of intracellular 35-S-labeled GAG storage, suggesting that some F48L-NAGLU was being correctly sorted to the lysosomal compartment. <a href="#18" class="mim-tip-reference" title="Yogalingam, G., Weber, B., Meehan, J., Rogers, J., Hopwood, J. J. <strong>Mucopolysaccharidosis type IIIB: characterisation and expression of wild-type and mutant recombinant alpha-N-acetylglucosaminidase and relationship with Sanfilippo phenotype in an attenuated patient.</strong> Biochim. Biophys. Acta 1502: 415-425, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11068184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11068184</a>] [<a href="https://doi.org/10.1016/s0925-4439(00)00066-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11068184">Yogalingam et al. (2000)</a> suggested that the residual NAGLU activity could explain the attenuated phenotype in their patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11068184" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0011 MUCOPOLYSACCHARIDOSIS, TYPE IIIB</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">rs104894600 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894600;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894600" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894600" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs118204025 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204025;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/rs118204025?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=rs118204025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs118204025" 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=RCV000001636 OR RCV001851559 OR RCV003894784" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001636, RCV001851559, RCV003894784" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001636...</a>
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<p>In 2 sibs with an attenuated form of Sanfilippo syndrome B (MPS3B; <a href="/entry/252920">252920</a>), <a href="#11" class="mim-tip-reference" title="Tanaka, A., Kimura, M., Lan, H. T. N., Takaura, N., Yamano, T. <strong>Molecular analysis of the alpha-N-acetylglucosaminidase gene in seven Japanese patients from six unrelated families with mucopolysaccharidosis IIIB (Sanfilippo type B), including two novel mutations.</strong> J. Hum. Genet. 47: 484-487, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12202988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12202988</a>] [<a href="https://doi.org/10.1007/s100380200070" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12202988">Tanaka et al. (2002)</a> identified compound heterozygosity for 2 mutations in the NAGLU gene: a phe314-to-leu (F314L) substitution and an R565P (<a href="#0009">609701.0009</a>) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12202988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs104894596 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894596;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/rs104894596?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=rs104894596" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894596" 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=RCV000001637 OR RCV001214384" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001637, RCV001214384" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001637...</a>
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<p>In a patient with a severe form of Sanfilippo syndrome B (MPS3B; <a href="/entry/252920">252920</a>), <a href="#11" class="mim-tip-reference" title="Tanaka, A., Kimura, M., Lan, H. T. N., Takaura, N., Yamano, T. <strong>Molecular analysis of the alpha-N-acetylglucosaminidase gene in seven Japanese patients from six unrelated families with mucopolysaccharidosis IIIB (Sanfilippo type B), including two novel mutations.</strong> J. Hum. Genet. 47: 484-487, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12202988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12202988</a>] [<a href="https://doi.org/10.1007/s100380200070" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12202988">Tanaka et al. (2002)</a> identified homozygosity for an arg482-to-trp (R482W) mutation in the NAGLU gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12202988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0013 MUCOPOLYSACCHARIDOSIS, TYPE IIIB</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> rs104894601 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894601;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/rs104894601?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=rs104894601" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894601" 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=RCV000001638 OR RCV001203422" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001638, RCV001203422" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001638...</a>
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<p>In patients with mucopolysaccharidosis type IIIB (MPS3B; <a href="/entry/252920">252920</a>), <a href="#1" class="mim-tip-reference" title="Beesley, C. E., Young, E. P., Vellodi, A., Winchester, B. G. <strong>Identification of 12 novel mutations in the alpha-N-acetylglucosaminidase gene in 14 patients with Sanfilippo syndrome type B (mucopolysaccharidosis type IIIB).</strong> J. Med. Genet. 35: 910-914, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9832037/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9832037</a>] [<a href="https://doi.org/10.1136/jmg.35.11.910" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9832037">Beesley et al. (1998)</a> identified a C-to-T transition in the NAGLU gene, resulting in an arg234-to-cys (R234C) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9832037" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#5" class="mim-tip-reference" title="Mangas, M., Nogueira, C., Prata, M. J., Lacerda, L., Coll, M. J., Soares, G., Ribeiro, G., Amaral, O., Ferreira, C., Alves, C., Coutinho, M. F., Alves, S. <strong>Molecular analysis of mucopolysaccharidosis type IIIB in Portugal: evidence of a single origin for a common mutation (R234C) in the Iberian Peninsula.</strong> Clin. Genet. 73: 251-256, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18218046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18218046</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00951.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18218046">Mangas et al. (2008)</a> identified the R234C mutation in 5 of 11 Portuguese patients with MPS3B. The mutation was the most common identified in this population, accounting for 32% of mutant alleles. Haplotype analysis showed that the R234C mutation arose on a founder haplotype common to both Spanish and Portuguese individuals. <a href="#5" class="mim-tip-reference" title="Mangas, M., Nogueira, C., Prata, M. J., Lacerda, L., Coll, M. J., Soares, G., Ribeiro, G., Amaral, O., Ferreira, C., Alves, C., Coutinho, M. F., Alves, S. <strong>Molecular analysis of mucopolysaccharidosis type IIIB in Portugal: evidence of a single origin for a common mutation (R234C) in the Iberian Peninsula.</strong> Clin. Genet. 73: 251-256, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18218046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18218046</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00951.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18218046">Mangas et al. (2008)</a> postulated that the mutation had a single and relatively recent origin in the Iberian peninsula. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18218046" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs104894598 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894598;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/rs104894598?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=rs104894598" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894598" 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=RCV000023780 OR RCV000433629 OR RCV000590258 OR RCV001043861" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023780, RCV000433629, RCV000590258, RCV001043861" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023780...</a>
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<p>In 3 affected children in family 8600486 with severe intellectual disability, autism spectrum disorder, and coarse facial features, diagnosed as mucopolysaccharidosis type IIIB (MPS3B; <a href="/entry/252920">252920</a>), <a href="#6" class="mim-tip-reference" title="Najmabadi, H., Hu, H., Garshasbi, M., Zemojtel, T., Abedini, S. S., Chen, W., Hosseini, M., Behjati, F., Haas, S., Jamali, P., Zecha, A., Mohseni, M., and 33 others. <strong>Deep sequencing reveals 50 novel genes for recessive cognitive disorders.</strong> Nature 478: 57-63, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21937992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21937992</a>] [<a href="https://doi.org/10.1038/nature10423" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21937992">Najmabadi et al. (2011)</a> identified a homozygous G-to-A transition in the NAGLU gene at genomic coordinate chr17:37949244 (NCBI36), resulting in an arg565-to-gln (R565Q) substitution. Their parents, who were first cousins once removed, were carriers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21937992" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0015 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2V (1 family)</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> rs796052122 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs796052122;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/rs796052122?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=rs796052122" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs796052122" 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=RCV000186582 OR RCV000423370 OR RCV001852433 OR RCV003479050" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000186582, RCV000423370, RCV001852433, RCV003479050" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000186582...</a>
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<p>In affected members of a large French Canadian kindred with autosomal dominant axonal Charcot-Marie-Tooth disease type 2V (CMT2V; <a href="/entry/616491">616491</a>), <a href="#13" class="mim-tip-reference" title="Tetreault, M., Gonzalez, M., Dicaire, M.-J., Allard, P., Gehring, K., Leblanc, D., Leclerc, N., Schondorf, R., Mathieu, J., Zuchner, S., Brais, B. <strong>Adult-onset painful axonal polyneuropathy caused by a dominant NAGLU mutation.</strong> Brain 138: 1477-1483, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25818867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25818867</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25818867[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/brain/awv074" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25818867">Tetreault et al. (2015)</a> identified a heterozygous c.1208T-C transition (c.1208T-C, NM_000263.3) in exon 6 of the NAGLU gene, resulting in an ile403-to-thr (I403T) substitution at a highly conserved residue in the Tim-barrel domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the dbSNP (build 137) or Exome Variant server databases, or in over 50 French Canadian controls. Patient leukocytes showed significantly decreased NAGLU enzyme activity (36-54% of controls), consistent with a detrimental effect of the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25818867" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0016 VARIANT OF UNKNOWN SIGNIFICANCE</strong>
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NAGLU, GLU123TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs796052123 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs796052123;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs796052123" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs796052123" 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=RCV000186583 OR RCV001382879" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000186583, RCV001382879" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000186583...</a>
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<p>This variant is classified as a variant of unknown significance because its contribution to Charcot-Marie-Tooth disease has not been confirmed.</p><p>In 3 members of a North American family with autosomal dominant axonal Charcot-Marie-Tooth disease (see CMT2V, <a href="/entry/616491">616491</a>), <a href="#13" class="mim-tip-reference" title="Tetreault, M., Gonzalez, M., Dicaire, M.-J., Allard, P., Gehring, K., Leblanc, D., Leclerc, N., Schondorf, R., Mathieu, J., Zuchner, S., Brais, B. <strong>Adult-onset painful axonal polyneuropathy caused by a dominant NAGLU mutation.</strong> Brain 138: 1477-1483, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25818867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25818867</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25818867[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/brain/awv074" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25818867">Tetreault et al. (2015)</a> identified a heterozygous mutation in the NAGLU gene, resulting in a glu123-to-ter (E123X) substitution. The substitution was predicted to truncate the protein before the catalytic domain, thus eliminating the possibility of residual enzyme activity, but functional studies were not performed. In addition, at least 1 affected family member also carried a heterozygous missense mutation (V243M) in the CMT-associated GDAP1 gene (<a href="/entry/606598">606598</a>), which was of uncertain significance; functional studies of the GDAP1 variant were not performed. These patients had onset of mild muscle weakness and pain in their teens, followed by distal sensory impairment in mid-adulthood. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25818867" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>REFERENCES</strong>
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<a id="Beesley1998" class="mim-anchor"></a>
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Beesley, C. E., Young, E. P., Vellodi, A., Winchester, B. G.
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<strong>Identification of 12 novel mutations in the alpha-N-acetylglucosaminidase gene in 14 patients with Sanfilippo syndrome type B (mucopolysaccharidosis type IIIB).</strong>
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J. Med. Genet. 35: 910-914, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9832037/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9832037</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9832037" 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/10.1136/jmg.35.11.910" target="_blank">Full Text</a>]
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Bunge, S., Knigge, A., Steglich, C., Kleijer, W. J., van Diggelen, O. P., Beck, M., Gal, A.
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<strong>Mucopolysaccharidosis type IIIB (Sanfilippo B): identification of 18 novel alpha-N-acetylglucosaminidase gene mutations.</strong>
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J. Med. Genet. 36: 28-31, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9950362/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9950362</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9950362" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Chinen, Y., Tohma, T., Izumikawa, Y., Uehara, H., Ohta, T.
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<strong>Sanfilippo type B syndrome: five patients with an R565P homozygous mutation in the alpha-N-acetylglucosaminidase gene from the Okinawa islands in Japan.</strong>
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J. Hum. Genet. 50: 357-359, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15933803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15933803</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15933803" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s10038-005-0258-4" target="_blank">Full Text</a>]
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Li, H. H., Yu, W.-H., Rozengurt, N., Zhao, H.-Z., Lyons, K. M., Anagnostaras, S., Fanselow, M. S., Suzuki, K., Vanier, M. T., Neufeld, E. F.
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<strong>Mouse model of Sanfilippo syndrome type B produced by targeted disruption of the gene encoding alpha-N-acetylglucosaminidase.</strong>
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Proc. Nat. Acad. Sci. 96: 14505-14510, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10588735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10588735</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10588735[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=10588735" 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.96.25.14505" target="_blank">Full Text</a>]
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Mangas, M., Nogueira, C., Prata, M. J., Lacerda, L., Coll, M. J., Soares, G., Ribeiro, G., Amaral, O., Ferreira, C., Alves, C., Coutinho, M. F., Alves, S.
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<strong>Molecular analysis of mucopolysaccharidosis type IIIB in Portugal: evidence of a single origin for a common mutation (R234C) in the Iberian Peninsula.</strong>
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Clin. Genet. 73: 251-256, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18218046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18218046</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18218046" 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.1399-0004.2007.00951.x" target="_blank">Full Text</a>]
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Najmabadi, H., Hu, H., Garshasbi, M., Zemojtel, T., Abedini, S. S., Chen, W., Hosseini, M., Behjati, F., Haas, S., Jamali, P., Zecha, A., Mohseni, M., and 33 others.
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<strong>Deep sequencing reveals 50 novel genes for recessive cognitive disorders.</strong>
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Nature 478: 57-63, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21937992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21937992</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21937992" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nature10423" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.1320200213" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2006.11.006" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1086/301685" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s100380200070" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/humu.1189" target="_blank">Full Text</a>]
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Cassandra L. Kniffin - updated : 7/28/2015
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Ada Hamosh - updated : 1/6/2012<br>Cassandra L. Kniffin - updated : 5/6/2008<br>Ada Hamosh - updated : 6/14/2007
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Cassandra L. Kniffin : 11/8/2005
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 06/21/2022
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<div class="row collapse" id="mimCollapseEditHistory">
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<span class="mim-text-font">
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carol : 07/29/2021<br>carol : 01/11/2016<br>alopez : 9/9/2015<br>mcolton : 8/3/2015<br>carol : 7/29/2015<br>mcolton : 7/28/2015<br>ckniffin : 7/28/2015<br>alopez : 5/14/2015<br>carol : 2/12/2014<br>mcolton : 2/12/2014<br>carol : 1/9/2012<br>carol : 1/9/2012<br>terry : 1/6/2012<br>wwang : 5/12/2008<br>ckniffin : 5/6/2008<br>alopez : 6/22/2007<br>terry : 6/14/2007<br>carol : 11/16/2005<br>carol : 11/16/2005<br>ckniffin : 11/8/2005
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<h3>
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<span class="mim-font">
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<strong>*</strong> 609701
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</span>
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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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N-ACETYLGLUCOSAMINIDASE, ALPHA-; NAGLU
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</span>
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</h3>
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<div>
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<br />
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<div >
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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>
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<span class="mim-font">
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N-ACETYL-ALPHA-D-GLUCOSAMINIDASE<br />
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N-ACETYL-ALPHA-GLUCOSAMINIDASE
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</span>
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</h4>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: NAGLU</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> 1187618009, 59990008;
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<strong>ICD10CM:</strong> E76.22;
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</p>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 17q21.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 17:42,536,241-42,544,449 </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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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<tbody>
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<td rowspan="2">
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<span class="mim-font">
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17q21.2
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<td>
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<span class="mim-font">
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?Charcot-Marie-Tooth disease, axonal, type 2V
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</td>
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<td>
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<span class="mim-font">
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616491
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<span class="mim-font">
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Autosomal dominant
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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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Mucopolysaccharidosis type IIIB (Sanfilippo B)
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</span>
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</td>
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<td>
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<span class="mim-font">
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252920
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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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</table>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Zhao et al. (1995) and Zhao et al. (1996) cloned a cDNA corresponding to alpha-N-acetylglucosaminidase, which they symbolized NAGLU. The deduced 743-amino acid protein has a 20- to 23-residue leader sequence, consistent with a signal peptide, and 6 potential N-glycosylation sites. The mature protein contains 720 amino acids and has a molecular mass of approximately 80 kD. </p><p>Weber et al. (1996) reported the cloning of the NAGLU gene by enzyme protein purification, amino acid sequence determination, and database searches. A TFASTA search aligned the amino acid sequence to sequence in the 5-prime flanking region of the 17-beta-hydroxysteroid dehydrogenase-1 gene (HSD17B1; 109684), and this sequence was used to screen cDNA libraries. Northern blot analysis showed a single 2.7-kb mRNA transcript with high expression levels in liver, ovary, and peripheral blood leukocytes and measurable amounts of transcript in other tissues. The full-length cDNA sequence was cloned into an expression vector, and cultured CHO cells transfected with this vector showed a 17-fold increase in enzyme expression. </p>
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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>Zhao et al. (1996) determined that the NAGLU gene contains 6 exons and spans 8.3 kb. </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>Zhao et al. (1996) mapped the NAGLU gene to chromosome 17q21. The 3-prime end of NAGLU resides in the upstream flanking region of the HSD17B1 gene. </p>
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</span>
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<div>
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<br />
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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>Vance et al. (1980) demonstrated variable alpha-N-acetylglucosaminidase activity levels among different groups of normal control populations, indicating polymorphisms within the gene that encodes the enzyme. Pericak-Vance et al. (1985) confirmed the polymorphisms reported by Vance et al. (1980) in studies of a large black kindred. They pointed out that alleles for high and low NAG enzyme activity might confuse the identification of heterozygotes. The mean values for NAG activity of the 3 genotypes varied in black and in white groups. Thermal stability data were cited suggesting that structurally distinct allelic forms of the enzyme may be segregating in the 2 racial groups. </p><p><strong><em>Mucopolysaccharidosis, Type IIIB</em></strong></p><p>
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Using SSCP analysis of PCR-amplified segments of genomic DNA from patients with Sanfilippo syndrome B, also known as mucopolysaccharidosis IIIB (MPS3B; 252920), Zhao et al. (1996) identified several recessive mutations in the NAGLU gene (see, e.g., 609701.0001-609701.0005). All missense mutations occurred at CpG sites, known to be mutagenic hotspots. </p><p>Zhao et al. (1998) stated that 36% of all known point mutations in the NAGLU gene causing MPS IIIB (8 of 22 alleles) involve arginine-674 (see, e.g., 609701.0001), a codon having a CpG dinucleotide in the critical initial position. </p><p>In 9 fibroblast cell lines of Sanfilippo syndrome B patients, Schmidtchen et al. (1998) identified 10 additional mutations in the NAGLU gene. Functional expression studies showed that the mutant enzymes had no residual activity. Nine of the 10 amino acid substitutions that had been identified to that time clustered near the amino or the carboxy end of the enzyme, suggesting a role for these regions in the transport or function of the protein. </p><p>Beesley et al. (1998) identified 12 novel mutations in the NAGLU gene in 14 patients with MPS IIIB. Bunge et al. (1999) identified 21 mutations, including 18 novel mutations, in the NAGLU gene in 22 patients with MPS IIIB. The mutation spectrum consisted of 2 small insertions, 2 small deletions, 3 nonsense mutations, and 14 different missense mutations, 1 of which affected the initiation codon. </p><p>In a study of 40 patients with Sanfilippo syndrome B, most of them of Australasian and Dutch origin, Weber et al. (1999) identified 31 mutations, 25 of them novel, and 2 polymorphisms in the NAGLU gene. The observed allelic heterogeneity reflected the wide spectrum of clinical phenotypes reported for these patients. Most of the changes were missense mutations; 4 nonsense and 9 frameshift mutations caused by insertions or deletions were also identified. Only 5 mutations were found in more than 1 patient. R643C (609701.0006) and R297X (609701.0003) each accounted for approximately 20% of MPS IIIB alleles in the Dutch patient group, while R297X, P521L (609701.0007), R565W (609701.0008), and R626X (609701.0002) each had a frequency of about 6% in Australasian patients. R643C seemed to be a Dutch MPS IIIB allele and clearly conferred an attenuated phenotype. One region of the gene showed a higher concentration of mutations, probably reflecting the instability of this area which contains a direct repeat. Several arginine residues seemed to be hotspots for mutations, being affected by 2 or 3 individual basepair exchanges (see 609701.0004 and 609701.0006). </p><p>In a mutation screen of 20 patients with Sanfilippo syndrome B, Tessitore et al. (2000) identified 28 mutations, 14 of which were novel, in the NAGLU gene. Of these mutations, 4 were found in homozygosity and only 1 was seen in 2 different patients, showing the remarkable molecular heterogeneity of the disorder. </p><p>Yogalingam and Hopwood (2001) reported that 86 new mutations had been identified in the NAGLU gene in MPS IIIB patients: 58 missense/nonsense mutations, 27 insertion/deletions, and 1 splice site mutation. All mutations were associated with severe clinical phenotypes. </p><p>Tanaka et al. (2002) performed molecular analysis of the NAGLU gene in 7 Japanese patients with Sanfilippo syndrome type B from 6 unrelated families; 6 disease-causing mutations were found, of which 2 were novel. Two families were from Okinawa, where more patients with Sanfilippo syndrome were found than in other areas in Japan. Two sibs, who were compound heterozygous for F314L (609701.0011) and R565P (609701.0009), showed an attenuated form. Two patients with a severe phenotype with rapid progression were homozygous for R482W (609701.0012) and R565P, respectively. Tanaka et al. (2002) suggested that the R565P mutation is common in Okinawa. Chinen et al. (2005) identified the homozygous R565P mutation in 5 unrelated Japanese patients from Okinawa, suggesting a founder effect. </p><p>Najmabadi et al. (2011) performed homozygosity mapping followed by exon enrichment and next-generation sequencing in 136 consanguineous families (over 90% Iranian and less than 10% Turkish or Arab) segregating syndromic or nonsyndromic forms of autosomal recessive intellectual disability. They identified a family (8600486) in which 3 of 4 children, born to parents related as first cousins once removed, had MPS IIIB (severe intellectual disability, autism spectrum disorder, and coarse facial features) and a homozygous missense mutation in the NAGLU gene (609701.0014). </p><p><strong><em>Charcot-Marie-Tooth Disease, Axonal, Type 2V</em></strong></p><p>
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In affected members of a large French Canadian kindred with autosomal dominant axonal Charcot-Marie-Tooth disease type 2V (CMT2V; 616491), Tetreault et al. (2015) identified a heterozygous missense mutation in the NAGLU gene (I403T; 609701.0015). The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family. Patient leukocytes showed significantly decreased NAGLU enzyme activity (36-54% of controls), consistent with a detrimental effect of the mutation. The patients had adult onset of progressive lower leg pain and distal sensory impairment. </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>Genotype/Phenotype Correlations</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In the study of Weber et al. (1999), all mutations resulting in premature termination either by a nonsense mutation or frameshift insertions and deletions led to the severe phenotype. Similarly, deletions masking the normal stop codon and presumably elongating the gene product conferred a severe phenotype when in combination with R297X. Missense mutations V334F and P521L also caused the severe phenotype when present on both alleles in individual patients. Most of the Dutch patients showed clinical symptoms consistent with the attenuated form of the disease. Two patients were diagnosed at the age of 63 and 47 years, respectively. Two of the attenuated cases, who were apparently not related, were found to be homozygous for R643C, an allele that was also identified in an attenuated patient with an unknown second allele. Two patients with R297X in combination with an unknown genotype (compound heterozygotes) had the severe and attenuated phenotype, respectively, implying that the unknown alleles modified the severity of the clinical phenotype. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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<span class="mim-text-font">
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<p>Li et al. (1999) found that Naglu-deficient mice were healthy and fertile while young and could survive for 8 to 12 months. They were totally deficient in alpha-N-acetylglucosaminidase and had massive accumulation of heparan sulfate in liver and kidney, as well as secondary changes in activity of several other lysosomal enzymes in liver and brain and elevation of gangliosides GM2 and GM3 in brain. Vacuolation was seen in many cells, including macrophages, epithelial cells, and neurons, and became more prominent with age. Although most vacuoles contained finely granular material characteristic of glycosaminoglycan accumulation, large pleiomorphic inclusions were seen in some neurons and pericytes in the brain. Abnormal hypoactive behavior was manifested by 4.5-month-old Naglu -/- mice in an open field test; the hyperactivity that is characteristic of affected children was not observed even in younger mice. In a pavlovian fear conditioning test, the 4.5-month-old mutant mice showed normal response to context, indicating intact hippocampal-dependent learning, but reduced response to a conditioning tone, perhaps attributable to hearing impairment. The phenotype of the deficient mice was considered sufficiently similar to that of patients with Sanfilippo syndrome B to make these mice a good model for study of pathophysiology and for development of therapy. </p><p>In mouse models, Ohmi et al. (2003) investigated the implications of microglial involvement for the pathogenesis as well as the potential treatment of MPS I (see 607014) and MPS IIIB. Their investigation showed an inflammatory component of brain disease in both disorders, as is known for many neurodegenerative disorders. </p><p>Ryazantsev et al. (2007) performed a detailed study of the brain pathology in mice deficient for the Naglu gene developed by Li et al. (1999). In contrast to somatic cells, which accumulate primarily heparan sulfate, neurons accumulate a number of apparently unrelated metabolites, including subunit c of mitochondrial ATPase synthase (SCMAS). SCMAS accumulated from 1 month of age, primarily in the medial entorhinal cortex and layer V of the somatosensory cortex. Its accumulation was not due to the absence of specific proteases. Light microscopy of brain sections of 6-month-old mice showed SCMAS to accumulate in the same organelles as Lamp1 (153330) and Lamp2 (309060). Cryoimmunoelectron microscopy showed SCMAS to be present in Lamp-positive vesicles bounded by a single membrane (lysosomes), in fingerprint-like layered arrays. GM3 ganglioside was also seen in lysosomes of microglia, suggesting phagocytosis of neuronal membranes. Samples used for cryoelectron microscopy and further processed by standard electron microscopy procedures showed the disappearance of the SCMAS fingerprint arrays and appearance in the same location of 'zebra bodies,' well known but little understood inclusions in the brain of patients with mucopolysaccharidosis. </p>
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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>16 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 IIIB</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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NAGLU, ARG674HIS
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<br />
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SNP: rs104894590,
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gnomAD: rs104894590,
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ClinVar: RCV000001626, RCV000078455, RCV000817080
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 Arab patients with Sanfilippo B syndrome, or mucopolysaccharidosis type IIIB (MPS3B; 252920), Zhao et al. (1996) identified a homozygous 2021G-A transition in the NAGLU gene, resulting in an arg674-to-his (R674H) substitution. </p>
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</span>
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</div>
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<div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 MUCOPOLYSACCHARIDOSIS, TYPE IIIB</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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NAGLU, ARG626TER
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<br />
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SNP: rs104894591,
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gnomAD: rs104894591,
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ClinVar: RCV000001627, RCV000153533, RCV000802847
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|
</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a cell line (GM156) from a patient with Sanfilippo syndrome B (MPS3B; 252920) from the Human Genetic Mutant Cell Repository, Zhao et al. (1996) identified a homozygous 1876C-T transition in the NAGLU gene, resulting in an arg626-to-ter (R626X) substitution. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
|
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</div>
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</div>
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|
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|
<div>
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|
|
<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 MUCOPOLYSACCHARIDOSIS, TYPE IIIB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
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<span class="mim-text-font">
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|
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|
NAGLU, ARG297TER
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|
<br />
|
|
|
|
SNP: rs104894592,
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|
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|
|
|
gnomAD: rs104894592,
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|
|
|
|
|
ClinVar: RCV000001628, RCV000485168, RCV001030805, RCV001041784
|
|
|
|
|
|
</span>
|
|
</div>
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|
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a cell line (GM156) from a patient with Sanfilippo syndrome B (MPS3B; 252920) from the Human Genetic Mutant Cell Repository, Zhao et al. (1996) identified compound heterozygosity for 2 mutations in the NAGLU gene: an 889C-T transition, resulting in an arg297-to-ter (R297X) substitution, and a G-to-A transition, resulting in an arg643-to-his (R643H; 609701.0004) substitution. </p><p>Weber et al. (1999) found that the R297X mutation was the most common mutation in a cohort of Dutch and Australasian MPS IIIB patients, occurring at a frequency of 12.5%. Yogalingam et al. (2000) found that this mutation was associated with very low levels of NAGLU activity and 12-fold elevations of 35-S-labeled GAG storage when compared with normal fibroblasts. </p>
|
|
</span>
|
|
</div>
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|
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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 IIIB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
<div>
|
|
<span class="mim-text-font">
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|
NAGLU, ARG643HIS
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|
<br />
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|
|
SNP: rs104894593,
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|
|
gnomAD: rs104894593,
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|
|
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|
|
ClinVar: RCV000001629, RCV001227283
|
|
|
|
|
|
</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg643-to-his (R643H) mutation in the NAGLU gene that was found in compound heterozygous state in a cell line (GM156) from a patient with Sanfilippo syndrome B (MPS3B; 252920) by Zhao et al. (1996), see 609701.0003. </p><p>Weber et al. (1999) reported that an R643C mutation (609701.0006) accounted for approximately 20% of MPS3B alleles in a Dutch patient group, suggesting that this arginine residue is a hotspot for mutations. </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 IIIB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NAGLU, 10-BP DEL, NT503
|
|
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|
|
<br />
|
|
|
|
SNP: rs483352897,
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|
|
|
|
|
gnomAD: rs483352897,
|
|
|
|
|
|
ClinVar: RCV000001630, RCV000626637, RCV001047802, RCV001588794
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In cell line from a patient with Sanfilippo syndrome B (MPS3B; 252920), Zhao et al. (1996) found homozygosity for a 10-bp deletion in the NAGLU gene beginning at nucleotide 503; the deletion resulted in a frameshift and predicted termination 14 codons later. The deletion occurs at a direct repeat of a tetranucleotide, GGAG, and may be the result of slipped mispairing during DNA replication. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 MUCOPOLYSACCHARIDOSIS, TYPE IIIB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NAGLU, ARG643CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894594,
|
|
|
|
|
|
gnomAD: rs104894594,
|
|
|
|
|
|
ClinVar: RCV000001631, RCV001030808, RCV001214750, RCV001579503
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Weber et al. (1999) reported that an arg643-to-cys (R643C) missense mutation in the NAGLU gene accounted for approximately 20% of mucopolysaccharidosis type IIIB (MPS3B; 252920) alleles in a Dutch patient group. Arginine-643 appears to be a hotspot for mutations; see R643H (609701.0004). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MUCOPOLYSACCHARIDOSIS, TYPE IIIB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NAGLU, PRO521LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894595,
|
|
|
|
|
|
gnomAD: rs104894595,
|
|
|
|
|
|
ClinVar: RCV000001632, RCV001030807, RCV001043674, RCV001729332
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Weber et al. (1999) found that a pro521-to-leu (P521L) missense mutation in the NAGLU gene accounted for approximately 6% of mutations in Australasian patients with Sanfilippo syndrome B (MPS3B; 252920). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 MUCOPOLYSACCHARIDOSIS, TYPE IIIB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NAGLU, ARG565TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894597,
|
|
|
|
|
|
gnomAD: rs104894597,
|
|
|
|
|
|
ClinVar: RCV000001633, RCV001223228, RCV002269255
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Weber et al. (1999) found that an arg565-to-trp (R565W) missense mutation accounted for approximately 6% of the mutant alleles in Australasian patients with Sanfilippo syndrome B (MPS3B; 252920). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 MUCOPOLYSACCHARIDOSIS, TYPE IIIB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NAGLU, ARG565PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894598,
|
|
|
|
|
|
gnomAD: rs104894598,
|
|
|
|
|
|
ClinVar: RCV000001634, RCV001851558
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Weber et al. (1999) observed an arg565-to-pro (R565P) mutation of the NAGLU gene in compound heterozygous state in a patient with Sanfilippo syndrome B (MPS3B; 252920). The arginine-565 residue appears to be a hotspot for mutations; see 609701.0008. </p><p>Tanaka et al. (2002) identified the R565P mutation in homozygous state in a patient with a severe form of Sanfilippo syndrome B. Tanaka et al. (2002) suggested that the R565P mutation may be common in Okinawa. </p><p>Chinen et al. (2005) identified the homozygous R565P mutation in 5 unrelated Japanese patients with Sanfilippo syndrome B, suggesting a founder effect. One of 200 control individuals was heterozygous for the mutation. The R565P substitution results from an 8839G-C transversion in exon 6 of the NAGLU gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MUCOPOLYSACCHARIDOSIS, TYPE IIIB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NAGLU, PHE48LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894599, rs118204024,
|
|
|
|
|
|
gnomAD: rs104894599,
|
|
|
|
|
|
ClinVar: RCV000001635, RCV002512655
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Yogalingam et al. (2000) reported a patient with an attenuated form of Sanfilippo syndrome B (MPS3B; 252920) who was a compound heterozygote for 2 mutations in the NAGLU gene: an R297X substitution (609701.0003) and a phe48-to-leu (F48L) substitution. The F48L mutation was associated with a partially degraded polypeptide in a 16-hour chase experiment, suggesting that this missense mutation affects the processing and stability of NAGLU. It was associated with significant residual NAGLU activity sufficient to metabolize 34% of intracellular 35-S-labeled GAG storage, suggesting that some F48L-NAGLU was being correctly sorted to the lysosomal compartment. Yogalingam et al. (2000) suggested that the residual NAGLU activity could explain the attenuated phenotype in their patient. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 MUCOPOLYSACCHARIDOSIS, TYPE IIIB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NAGLU, PHE314LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894600, rs118204025,
|
|
|
|
|
|
gnomAD: rs118204025,
|
|
|
|
|
|
ClinVar: RCV000001636, RCV001851559, RCV003894784
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs with an attenuated form of Sanfilippo syndrome B (MPS3B; 252920), Tanaka et al. (2002) identified compound heterozygosity for 2 mutations in the NAGLU gene: a phe314-to-leu (F314L) substitution and an R565P (609701.0009) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 MUCOPOLYSACCHARIDOSIS, TYPE IIIB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NAGLU, ARG482TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894596,
|
|
|
|
|
|
gnomAD: rs104894596,
|
|
|
|
|
|
ClinVar: RCV000001637, RCV001214384
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with a severe form of Sanfilippo syndrome B (MPS3B; 252920), Tanaka et al. (2002) identified homozygosity for an arg482-to-trp (R482W) mutation in the NAGLU gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 MUCOPOLYSACCHARIDOSIS, TYPE IIIB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NAGLU, ARG234CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894601,
|
|
|
|
|
|
gnomAD: rs104894601,
|
|
|
|
|
|
ClinVar: RCV000001638, RCV001203422
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In patients with mucopolysaccharidosis type IIIB (MPS3B; 252920), Beesley et al. (1998) identified a C-to-T transition in the NAGLU gene, resulting in an arg234-to-cys (R234C) substitution. </p><p>Mangas et al. (2008) identified the R234C mutation in 5 of 11 Portuguese patients with MPS3B. The mutation was the most common identified in this population, accounting for 32% of mutant alleles. Haplotype analysis showed that the R234C mutation arose on a founder haplotype common to both Spanish and Portuguese individuals. Mangas et al. (2008) postulated that the mutation had a single and relatively recent origin in the Iberian peninsula. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 MUCOPOLYSACCHARIDOSIS, TYPE IIIB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NAGLU, ARG565GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894598,
|
|
|
|
|
|
gnomAD: rs104894598,
|
|
|
|
|
|
ClinVar: RCV000023780, RCV000433629, RCV000590258, RCV001043861
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 affected children in family 8600486 with severe intellectual disability, autism spectrum disorder, and coarse facial features, diagnosed as mucopolysaccharidosis type IIIB (MPS3B; 252920), Najmabadi et al. (2011) identified a homozygous G-to-A transition in the NAGLU gene at genomic coordinate chr17:37949244 (NCBI36), resulting in an arg565-to-gln (R565Q) substitution. Their parents, who were first cousins once removed, were carriers. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2V (1 family)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NAGLU, ILE403THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs796052122,
|
|
|
|
|
|
gnomAD: rs796052122,
|
|
|
|
|
|
ClinVar: RCV000186582, RCV000423370, RCV001852433, RCV003479050
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
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<p>In affected members of a large French Canadian kindred with autosomal dominant axonal Charcot-Marie-Tooth disease type 2V (CMT2V; 616491), Tetreault et al. (2015) identified a heterozygous c.1208T-C transition (c.1208T-C, NM_000263.3) in exon 6 of the NAGLU gene, resulting in an ile403-to-thr (I403T) substitution at a highly conserved residue in the Tim-barrel domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the dbSNP (build 137) or Exome Variant server databases, or in over 50 French Canadian controls. Patient leukocytes showed significantly decreased NAGLU enzyme activity (36-54% of controls), consistent with a detrimental effect of the mutation. </p>
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<h4>
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<span class="mim-font">
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<strong>.0016 VARIANT OF UNKNOWN SIGNIFICANCE</strong>
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</h4>
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NAGLU, GLU123TER
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<br />
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SNP: rs796052123,
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ClinVar: RCV000186583, RCV001382879
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<p>This variant is classified as a variant of unknown significance because its contribution to Charcot-Marie-Tooth disease has not been confirmed.</p><p>In 3 members of a North American family with autosomal dominant axonal Charcot-Marie-Tooth disease (see CMT2V, 616491), Tetreault et al. (2015) identified a heterozygous mutation in the NAGLU gene, resulting in a glu123-to-ter (E123X) substitution. The substitution was predicted to truncate the protein before the catalytic domain, thus eliminating the possibility of residual enzyme activity, but functional studies were not performed. In addition, at least 1 affected family member also carried a heterozygous missense mutation (V243M) in the CMT-associated GDAP1 gene (606598), which was of uncertain significance; functional studies of the GDAP1 variant were not performed. These patients had onset of mild muscle weakness and pain in their teens, followed by distal sensory impairment in mid-adulthood. </p>
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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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Bunge, S., Knigge, A., Steglich, C., Kleijer, W. J., van Diggelen, O. P., Beck, M., Gal, A.
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<p class="mim-text-font">
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Zhao, H. G., Li, H. H., Bach, G., Schmidtchen, A., Neufeld, E. F.
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<strong>The molecular basis of Sanfilippo syndrome type B.</strong>
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Zhao, H. G., Li, H. H., Schmidtchen, A., Bach, G., Neufeld, E. F.
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<strong>The gene encoding alpha-N-acetylglucosaminidase and mutations underlying Sanfilippo B syndrome. (Abstract)</strong>
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Am. J. Hum. Genet. 57: A185 only, 1995.
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Cassandra L. Kniffin - updated : 7/28/2015<br>Ada Hamosh - updated : 1/6/2012<br>Cassandra L. Kniffin - updated : 5/6/2008<br>Ada Hamosh - updated : 6/14/2007
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