4879 lines
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- *607840 - N-ACETYLGLUCOSAMINE-1-PHOSPHOTRANSFERASE, ALPHA/BETA SUBUNITS; GNPTAB
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*607840</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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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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</li>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/607840">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000111670;t=ENST00000299314" 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=79158" 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=607840" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000111670;t=ENST00000299314" 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_024312,XM_006719593,XM_011538731" 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_024312" 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=607840" 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=11350&isoform_id=11350_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/GNPTAB" 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/7023329,8655650,12803871,16551459,20521792,27769329,38202211,47939526,51491302,56567275,63101698,74474848,90185244,119618088,119618089,119618090,124298022,578824215,767975294,2441007238,2462534338,2462534340" 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/Q3T906" 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=79158" 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=ENSG00000111670;t=ENST00000299314" 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=GNPTAB" 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=GNPTAB" 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+79158" 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/GNPTAB" 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:79158" 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/79158" 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=chr12&hgg_gene=ENST00000299314.12&hgg_start=101745499&hgg_end=101830959&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:29670" 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/gnptab" 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=607840[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
|
|
</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=607840[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/GNPTAB/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000111670" 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=GNPTAB" 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=GNPTAB" 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=GNPTAB" 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=GNPTAB&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/PA128394710" 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:29670" 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/FBgn0033392.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:3643902" 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/GNPTAB#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:3643902" 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/79158/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/OMIA001248/" 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=79158" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-030131-4714" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
|
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
|
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</div>
|
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</a>
|
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</span>
|
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</span>
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</div>
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<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:607840" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<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:79158" 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=GNPTAB&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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|
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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> 65764006<br />
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">ICD+</a>
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</div>
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<div>
|
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
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607840
|
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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-ACETYLGLUCOSAMINE-1-PHOSPHOTRANSFERASE, ALPHA/BETA SUBUNITS; GNPTAB
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</span>
|
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</h3>
|
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</div>
|
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
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<p>
|
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<span class="mim-font">
|
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
|
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</div>
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
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GNPTA<br />
|
|
MGC4170
|
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</span>
|
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</h4>
|
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</div>
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</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=GNPTAB" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">GNPTAB</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/12/731?start=-3&limit=10&highlight=731">12q23.2</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr12:101745499-101830959&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'})">12:101,745,499-101,830,959</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
|
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|
|
</span>
|
|
</p>
|
|
</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=252500,252600" 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/12/731?start=-3&limit=10&highlight=731">
|
|
12q23.2
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Mucolipidosis II alpha/beta
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/252500"> 252500 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
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PheneGene Graphics <span class="caret"></span>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<p>UDP-N-acetylglucosamine:lysosomal-enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase; <a href="https://enzyme.expasy.org/EC/2.7.8.17" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 2.7.8.17</a>) catalyzes the initial step in the synthesis of the mannose 6-phosphate determinant required for efficient intracellular targeting of newly synthesized lysosomal hydrolases to the lysosome. GlcNAc-phosphotransferase is an alpha-2/beta-2/gamma-2 hexameric complex. The GNPTAB gene encodes both the alpha and beta subunits; the gamma subunit is encoded by the GNPTG gene (<a href="/entry/607838">607838</a>).</p>
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<p>Bao et al. (<a href="#1" class="mim-tip-reference" title="Bao, M., Booth, J. L., Elmendorf, B. J., Canfield, W. M. <strong>Bovine UDP-N-acetylglucosamine:lysosomal-enzyme N-acetylglucosamine-1-phosphotransferase: I. Purification and subunit structure.</strong> J. Biol. Chem. 271: 31437-31445, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8940155/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8940155</a>] [<a href="https://doi.org/10.1074/jbc.271.49.31437" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8940155">1996</a>, <a href="#2" class="mim-tip-reference" title="Bao, M., Elmendorf, B. J., Booth, J. L., Drake, R. R., Canfield, W. M. <strong>Bovine UDP-N-acetylglucosamine:lysosomal-enzyme N-acetylglucosamine-1-phosphotransferase: II. Enzymatic characterization and identification of the catalytic subunit.</strong> J. Biol. Chem. 271: 31446-31451, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8940156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8940156</a>] [<a href="https://doi.org/10.1074/jbc.271.49.31446" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8940156">1996</a>) determined that bovine GlcNAc-phosphotransferase is a 54-kD alpha-2/beta-2/gamma-2 hexameric complex. <a href="#5" class="mim-tip-reference" title="Canfield, W. M., Bao, M., Pan, J., Brewer, A. D. K., Pan, H., Roe, B., Raas-Rothschild, A. <strong>Mucolipidosis II and mucolipidosis IIIA are caused by mutations in the GlcNAc-phosphotransferase alpha/beta gene on chromosome 12p. (Abstract)</strong> Am. J. Hum. Genet. 63: A15 only, 1998."None>Canfield et al. (1998)</a> indicated that the alpha and beta subunits are derived from a single cDNA. The individual subunits are apparently generated by proteolytic processing at a lys-asp bond following synthesis of an alpha/beta precursor, generating a 928-amino acid N-terminal alpha subunit and a 328-amino acid C-terminal beta subunit. The gamma subunit is encoded by a separate gene (GNPTG; <a href="/entry/607838">607838</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8940156+8940155" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By database analysis, <a href="#21" class="mim-tip-reference" title="Tiede, S., Storch, S., Lubke, T., Henrissat, B., Bargal, R., Raas-Rothschild, A., Braulke, T. <strong>Mucolipidosis II is caused by mutations in GNPTA encoding the alpha/beta GlcNAc-1-phosphotransferase.</strong> Nature Med. 11: 1109-1112, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16200072/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16200072</a>] [<a href="https://doi.org/10.1038/nm1305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16200072">Tiede et al. (2005)</a> identified the human GNPTAB gene. The deduced 1256-amino acid protein has a predicted molecular mass of 144 kD. Hydrophobicity analysis showed 2 transmembrane domains and 19 potential N-glycosylation sites. Sequence comparisons showed that GNPTAB has a complex modular structure composed of at least 6 domains including an N-terminal domain with a putative nucleotide binding site, 2 Notch repeat-like domains, and a DMAP1 (<a href="/entry/605077">605077</a>) binding-like domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16200072" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By database analysis, <a href="#21" class="mim-tip-reference" title="Tiede, S., Storch, S., Lubke, T., Henrissat, B., Bargal, R., Raas-Rothschild, A., Braulke, T. <strong>Mucolipidosis II is caused by mutations in GNPTA encoding the alpha/beta GlcNAc-1-phosphotransferase.</strong> Nature Med. 11: 1109-1112, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16200072/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16200072</a>] [<a href="https://doi.org/10.1038/nm1305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16200072">Tiede et al. (2005)</a> determined that the GNPTAB gene contains 21 exons and spans 85 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16200072" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="#22" class="mim-tip-reference" title="Vidgoff, J., Rowe, S., Stafford, R., Buist, N. R. M., Lovrien, E. W. <strong>Localization of the gene for I-cell disease (mucolipidosis II). (Abstract)</strong> Am. J. Hum. Genet. 34: 64A, 1982."None>Vidgoff et al. (1982)</a> found possible linkage of ML II to MN (<a href="/entry/111300">111300</a>) on 4q, with a lod score of 1.3. <a href="#14" class="mim-tip-reference" title="Mueller, O. T., Wasmuth, J. J., Murray, J. C., Lozzio, C. B., Lovrien, E. W., Shows, T. B. <strong>Chromosomal assignment of N-acetylglucosaminylphosphotransferase, the lysosomal hydrolase targeting enzyme deficient in mucolipidosis II and III. (Abstract)</strong> Cytogenet. Cell Genet. 46: 664, 1987."None>Mueller et al. (1987)</a> determined the chromosome assignment of the structural gene altered in the common forms of ML II and ML III by linkage analysis, somatic cell hybrids, and gene dosage. Linkage data with ML II families indicated that the ML II locus is located between GC (<a href="/entry/139200">139200</a>) and MNS. The combined data indicated that GNPTA maps to 4q21-q23.</p><p>By genomic sequence analysis, <a href="#21" class="mim-tip-reference" title="Tiede, S., Storch, S., Lubke, T., Henrissat, B., Bargal, R., Raas-Rothschild, A., Braulke, T. <strong>Mucolipidosis II is caused by mutations in GNPTA encoding the alpha/beta GlcNAc-1-phosphotransferase.</strong> Nature Med. 11: 1109-1112, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16200072/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16200072</a>] [<a href="https://doi.org/10.1038/nm1305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16200072">Tiede et al. (2005)</a> mapped the GNPTAB gene to chromosome 12q23.3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16200072" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Paton, L., Bitoun, E., Kenyon, J., Priestman, D. A., Oliver, P. L., Edwards, B., Platt, F. M., Davies, K. E. <strong>A novel mouse model of a patient mucolipidosis II mutation recapitulates disease pathology.</strong> J. Biol. Chem. 289: 26709-26721, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25107912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25107912</a>] [<a href="https://doi.org/10.1074/jbc.M114.586156" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25107912">Paton et al. (2014)</a> stated that the mouse Gnptab gene maps to chromosome 10. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25107912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="Canfield, W. M., Bao, M., Pan, J., Brewer, A. D. K., Pan, H., Roe, B., Raas-Rothschild, A. <strong>Mucolipidosis II and mucolipidosis IIIA are caused by mutations in the GlcNAc-phosphotransferase alpha/beta gene on chromosome 12p. (Abstract)</strong> Am. J. Hum. Genet. 63: A15 only, 1998."None>Canfield et al. (1998)</a> found that in 4 of 4 patients with mucolipidosis II (ML II; <a href="/entry/252500">252500</a>), the 6.2-kb alpha/beta transcript was absent. In 2 of 2 patients with mucolipidosis IIIA (<a href="/entry/252600">252600</a>), the alpha/beta transcript was present but greatly reduced. In all patients examined, the gamma transcript was present at normal levels.</p><p>By retroviral transduction of fibroblasts from an individual with mucolipidosis II, <a href="#21" class="mim-tip-reference" title="Tiede, S., Storch, S., Lubke, T., Henrissat, B., Bargal, R., Raas-Rothschild, A., Braulke, T. <strong>Mucolipidosis II is caused by mutations in GNPTA encoding the alpha/beta GlcNAc-1-phosphotransferase.</strong> Nature Med. 11: 1109-1112, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16200072/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16200072</a>] [<a href="https://doi.org/10.1038/nm1305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16200072">Tiede et al. (2005)</a> demonstrated expression and localization of GNPTAB in the Golgi apparatus, accompanied by correction of the hypersecretion of lysosomal enzymes. <a href="#21" class="mim-tip-reference" title="Tiede, S., Storch, S., Lubke, T., Henrissat, B., Bargal, R., Raas-Rothschild, A., Braulke, T. <strong>Mucolipidosis II is caused by mutations in GNPTA encoding the alpha/beta GlcNAc-1-phosphotransferase.</strong> Nature Med. 11: 1109-1112, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16200072/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16200072</a>] [<a href="https://doi.org/10.1038/nm1305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16200072">Tiede et al. (2005)</a> concluded that GNPTAB encodes a subunit of GlcNAc-phosphotransferase that is defective in individuals with ML II. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16200072" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Kudo, M., Bao, M., D'Souza, A., Ying, F., Pan, H., Roe, B. A., Canfield, W. M. <strong>The alpha- and beta-subunits of the human UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase are encoded by a single cDNA.</strong> J. Biol. Chem. 280: 36141-36149, 2005. Note: Erratum: J. Biol. Chem. 280: 42476 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16120602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16120602</a>] [<a href="https://doi.org/10.1074/jbc.M509008200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16120602">Kudo et al. (2005)</a> cloned the cDNA and genomic DNA encoding the alpha/beta-subunits precursor gene (GNPTAB). With the cloning of the gamma-subunit gene (GNPTG; <a href="/entry/607838">607838</a>), it could be concluded that GlcNAc-phosphotransferase is the product of 2 genes, an uncommon exception to the Garrod-Beadle principle of 1 enzyme-1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16120602" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#13" class="mim-tip-reference" title="Marschner, K., Kollmann, K., Schweizer, M., Braulke, T., Pohl, S. <strong>A key enzyme in the biogenesis of lysosomes is a protease that regulates cholesterol metabolism.</strong> Science 333: 87-90, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21719679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21719679</a>] [<a href="https://doi.org/10.1126/science.1205677" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21719679">Marschner et al. (2011)</a> found that the alpha/beta subunit of the N-acetylglucosamine-1-phosphotransferase complex is cleaved by the site-1 protease (S1P; <a href="/entry/603355">603355</a>) that activates sterol regulatory element-binding proteins in response to cholesterol deprivation. S1P-deficient cells failed to activate the alpha/beta subunit precursor and exhibited a mucolipidosis II-like phenotype. Thus, <a href="#13" class="mim-tip-reference" title="Marschner, K., Kollmann, K., Schweizer, M., Braulke, T., Pohl, S. <strong>A key enzyme in the biogenesis of lysosomes is a protease that regulates cholesterol metabolism.</strong> Science 333: 87-90, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21719679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21719679</a>] [<a href="https://doi.org/10.1126/science.1205677" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21719679">Marschner et al. (2011)</a> concluded that S1P functions in the biogenesis of lysosomes, and that lipid-independent phenotypes of S1P deficiency may be caused by lysosomal dysfunction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21719679" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a 47-year-old female who presented with dilated cardiomyopathy and mild neuropathy and was found to have mucolipidosis III (<a href="/entry/252600">252600</a>), <a href="#19" class="mim-tip-reference" title="Steet, R. A., Hullin, R., Kudo, M., Martinelli, M., Bosshard, N. U., Schaffner, T., Kornfeld, S. Steinmann, B. <strong>A splicing mutation in the alpha/beta GlcNAc-1-phosphotransferase gene results in an adult onset form of mucolipidosis III associated with sensory neuropathy and cardiomyopathy.</strong> Am. J. Med. Genet. 132A: 369-375, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15633164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15633164</a>] [<a href="https://doi.org/10.1002/ajmg.a.30498" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15633164">Steet et al. (2005)</a> identified a homozygous splice site mutation of the GNPTAB gene (<a href="#0001">607840.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15633164" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 14-year-old boy with a mild clinical phenotype of mucolipidosis III, <a href="#20" class="mim-tip-reference" title="Tiede, S., Muschol, N., Reutter, G., Cantz, M., Ullrich, K., Braulke, T. <strong>Missense mutations in N-acetylglucosamine-1-phosphotransferase alpha/beta subunit gene in a patient with mucolipidosis III and a mild clinical phenotype.</strong> Am. J. Med. Genet. 137A: 235-240, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16094673/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16094673</a>] [<a href="https://doi.org/10.1002/ajmg.a.30868" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16094673">Tiede et al. (2005)</a> identified homozygosity for an asp407-to-ala substitution in the GNPTAB gene (<a href="#0002">607840.0002</a>). The patient was also homozygous for an ala663-to-gly substitution in the GNPTAB that was deemed a polymorphism because it was found in 5% of normal alleles. Both parents were heterozygous for both mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16094673" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 unrelated Korean girls with mucolipidosis II (<a href="/entry/252500">252500</a>) and 2 unrelated Korean girls with mucolipidosis IIIA, <a href="#16" class="mim-tip-reference" title="Paik, K. H., Song, S. M., Ki, C. S., Yu, H.-W., Kim, J. S., Min, K. H., Chang, S. H., Yoo, E. J., Lee, I. J., Kwan, E. K., Han, S. J., Jin, D.-K. <strong>Identification of mutations in the GNPTA (MGC4170) gene coding for GlcNAc-phosphotransferase alpha/beta subunits in Korean patients with mucolipidosis type II or type IIIA.</strong> Hum. Mutat. 26: 308-314, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16116615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16116615</a>] [<a href="https://doi.org/10.1002/humu.20205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16116615">Paik et al. (2005)</a> identified compound heterozygosity for 7 different mutations in the GNPTAB gene (<a href="#0003">607840.0003</a>-<a href="#0009">607840.0009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16116615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 6 patients with clinically and biochemically diagnosed mucolipidosis II, <a href="#21" class="mim-tip-reference" title="Tiede, S., Storch, S., Lubke, T., Henrissat, B., Bargal, R., Raas-Rothschild, A., Braulke, T. <strong>Mucolipidosis II is caused by mutations in GNPTA encoding the alpha/beta GlcNAc-1-phosphotransferase.</strong> Nature Med. 11: 1109-1112, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16200072/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16200072</a>] [<a href="https://doi.org/10.1038/nm1305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16200072">Tiede et al. (2005)</a> identified homozygosity or compound heterozygosity for 7 mutations in the GNPTAB gene, all resulting in premature translational termination (e.g., <a href="#0010">607840.0010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16200072" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To determine whether mucolipidosis II, or I-cell disease, and mucolipidosis IIIA, or classic pseudo-Hurler polydystrophy, are caused by mutations in the gene encoding the alpha/beta-subunits precursor gene, <a href="#12" class="mim-tip-reference" title="Kudo, M., Brem, M. S., Canfield, W. M. <strong>Mucolipidosis II (I-cell disease) and mucolipidosis IIIA (classical pseudo-Hurler polydystrophy) are caused by mutations in the GlcNAc-phosphotransferase alpha/beta-subunits precursor gene.</strong> Am. J. Hum. Genet. 78: 451-463, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16465621/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16465621</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16465621[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/500849" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16465621">Kudo et al. (2006)</a> sequenced GNPTAB exons and flanking intronic sequences and measured GlcNAc-phosphotransferase activity in patient fibroblasts. They identified 15 different mutations in GNPTAB from 18 pedigrees with one or the other of these 2 diseases and demonstrated that these 2 diseases are allelic. Mutations in both alleles were identified in each case, which demonstrated that GNPTAB mutations are the cause of both diseases. Some pedigrees had identical mutations. A 2-bp deletion (<a href="#0011">607840.0011</a>), resulting in a frameshift and premature termination, predominated and was found in both ML II and ML IIIA. This mutation was found in combination with severe mutations (i.e., mutations preventing the generation of active enzyme) in ML II and with mild mutations (i.e., mutations allowing the generation of active enzyme) in ML IIIA. Some cases of ML II and ML IIIA were the result of mutations that cause aberrant splicing. Substitutions were within the invariant splice site sequence in ML II and were outside it in ML IIIA. When the mutations were analyzed along with GlcNAc-phosphotransferase activity, it was possible to distinguish with confidence these 2 related but distinct disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16465621" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Bargal, R., Zeigler, M., Abu-Libdeh, B., Zuri, V., Mandel, H., Neriah, Z. B., Stewart, F., Elcioglu, N., Hindi, T., Le Merrer, M., Bach, G., Raas-Rothschild, A. <strong>When mucolipidosis III meets mucolipidosis II: GNPTA gene mutations in 24 patients.</strong> Molec. Genet. Metab. 88: 359-363, 2006. Note: Erratum: Molec. Genet. Metab. 91: 299 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16630736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16630736</a>] [<a href="https://doi.org/10.1016/j.ymgme.2006.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16630736">Bargal et al. (2006)</a> studied GNPTAB mutations in 24 patients. They suggested that there is a clinical continuum between ML III and ML II, and the classification of these diseases should be based on the age of onset, clinical symptoms, and severity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16630736" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Associations Pending Confirmation</em></strong></p><p>
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In affected members of a large consanguineous 6-generation Pakistani family with stuttering (STUT2; <a href="/entry/609261">609261</a>) showing linkage to chromosome 12q, <a href="#10" class="mim-tip-reference" title="Kang, C., Riazuddin, S., Mundorff, J., Krasnewich, D., Friedman, P., Mullikin, J. C., Drayna, D. <strong>Mutations in the lysosomal enzyme-targeting pathway and persistent stuttering.</strong> New Eng. J. Med. 362: 677-685, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20147709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20147709</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20147709[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1056/NEJMoa0902630" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20147709">Kang et al. (2010)</a> identified a glu1200-to-lys (E1200K) variant in the GNPTAB gene. Thirteen affected individuals were heterozygous, and 12 were homozygous. However, the variant did not completely segregate with the disorder: 3 noncarriers were affected, and 2 homozygous E1200K carriers and 9 heterozygous E1200K carriers were unaffected. <a href="#10" class="mim-tip-reference" title="Kang, C., Riazuddin, S., Mundorff, J., Krasnewich, D., Friedman, P., Mullikin, J. C., Drayna, D. <strong>Mutations in the lysosomal enzyme-targeting pathway and persistent stuttering.</strong> New Eng. J. Med. 362: 677-685, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20147709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20147709</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20147709[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1056/NEJMoa0902630" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20147709">Kang et al. (2010)</a> suggested nonpenetrance in these individuals. The authors identified 3 additional variants in the GNPTAB gene in 4 additional unrelated individuals with stuttering. None of the individuals had features of mucolipidosis. Study of additional families and individuals identified the E1200K variant in 3 other Pakistani families with stuttering, in 1 North American patient of Asian Indian ancestry, and in 1 Pakistani control. The E1200K variant was not found in 192 chromosomes from unaffected Pakistani controls or in 552 chromosomes from North American controls. By studying other genes in the lysosomal enzyme-targeting pathway, <a href="#10" class="mim-tip-reference" title="Kang, C., Riazuddin, S., Mundorff, J., Krasnewich, D., Friedman, P., Mullikin, J. C., Drayna, D. <strong>Mutations in the lysosomal enzyme-targeting pathway and persistent stuttering.</strong> New Eng. J. Med. 362: 677-685, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20147709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20147709</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20147709[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1056/NEJMoa0902630" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20147709">Kang et al. (2010)</a> identified 3 variants each in the GNPTG (<a href="/entry/607838">607838</a>) and NAGPA (<a href="/entry/607985">607985</a>) genes that were found in 11 of 270 North American/British patients with stuttering but not in 276 controls. <a href="#10" class="mim-tip-reference" title="Kang, C., Riazuddin, S., Mundorff, J., Krasnewich, D., Friedman, P., Mullikin, J. C., Drayna, D. <strong>Mutations in the lysosomal enzyme-targeting pathway and persistent stuttering.</strong> New Eng. J. Med. 362: 677-685, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20147709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20147709</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20147709[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1056/NEJMoa0902630" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20147709">Kang et al. (2010)</a> concluded that variations in genes governing lysosomal metabolism may be susceptibility factors for nonsyndromic persistent stuttering. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20147709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By haplotype analysis of 8 unrelated individuals who were heterozygous or homozygous for the G1200K variant, <a href="#9" class="mim-tip-reference" title="Fedyna, A., Drayna, D., Kang, C. <strong>Characterization of a mutation commonly associated with persistent stuttering: evidence for a founder mutation.</strong> J. Hum. Genet. 56: 80-82, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20944643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20944643</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20944643[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/10.1038/jhg.2010.125" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20944643">Fedyna et al. (2011)</a> determined that it arose as a founder allele 572 generations, or 14,300 years ago. Haplotype analysis identified a common 6.67-kb haplotype containing the variant. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20944643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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="#15" class="mim-tip-reference" title="Otomo, T., Muramatsu, T., Yorifuji, T., Okuyama, T., Nakabayashi, H., Fukao, T., Ohura, T., Yoshino, M., Tanaka, A., Okamoto, N., Inui, K., Ozono, K., Sakai, N. <strong>Mucolipidosis II and III alpha/beta: mutation analysis of 40 Japanese patients showed genotype-phenotype correlation.</strong> J. Hum. Genet. 54: 145-151, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19197337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19197337</a>] [<a href="https://doi.org/10.1038/jhg.2009.3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19197337">Otomo et al. (2009)</a> identified 18 GNPTAB mutations, including 14 novel mutations, among 25 unrelated Japanese patients with ML II and 15 Japanese patients with ML III. The most common mutations were R1189X (<a href="#0004">607840.0004</a>), which was found in 41% of alleles, and F374L (<a href="#0015">607840.0015</a>), which was found in 10% of alleles. Homozygotes or compound heterozygotes of nonsense and frameshift mutations contributed to the more severe phenotype. In all, 73 GNPTAB mutations were detected in the 80 alleles. In a review of the reported clinical features, most ML II patients had impairment in standing alone, walking without support, and speaking single words compared to those with ML III. The frequencies of heart murmur, inguinal hernia, and hepatomegaly and/or splenomegaly did not differ between ML II and III patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19197337" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Encarnacao, M., Lacerda, L., Costa, R., Prata, M. J., Coutinho, M. F., Ribeiro, H., Lopes, L., Pineda, M., Ignatius, J., Galvez, H., Mustonen, A., Vieira, P., Lima, M. R., Alves, S. <strong>Molecular analysis of the GNPTAB and GNPTG genes in 13 patients with mucolipidosis type II or type III - identification of eight novel mutations.</strong> Clin. Genet. 76: 76-84, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19659762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19659762</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2009.01185.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19659762">Encarnacao et al. (2009)</a> identified GNPTAB mutations in 9 mostly Portuguese patients with ML II. Eight of 9 patients had a nonsense or frameshift mutation, the most common being a 2-bp deletion (<a href="#0011">607840.0011</a>) that was found in 45% of the mutant alleles; one patient with ML II was homozygous for a missense mutation. Three additional patients with a less severe phenotype consistent with ML III had missense mutations. <a href="#8" class="mim-tip-reference" title="Encarnacao, M., Lacerda, L., Costa, R., Prata, M. J., Coutinho, M. F., Ribeiro, H., Lopes, L., Pineda, M., Ignatius, J., Galvez, H., Mustonen, A., Vieira, P., Lima, M. R., Alves, S. <strong>Molecular analysis of the GNPTAB and GNPTG genes in 13 patients with mucolipidosis type II or type III - identification of eight novel mutations.</strong> Clin. Genet. 76: 76-84, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19659762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19659762</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2009.01185.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19659762">Encarnacao et al. (2009)</a> concluded that patients with ML II alpha/beta are almost all associated with the presence of nonsense or frameshift mutations in homozygosity, whereas the presence of at least 1 mild mutation in the GNPTAB gene is associated with ML III alpha/beta. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19659762" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Cathey, S. S., Leroy, J. G., Wood, T., Eaves, K., Simensen, R. J., Kudo, M., Stevenson, R. E., Friez, M. J. <strong>Phenotype and genotype in mucolipidoses II and III alpha/beta: a study of 61 probands.</strong> J. Med. Genet. 47: 38-48, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19617216/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19617216</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19617216[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/10.1136/jmg.2009.067736" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19617216">Cathey et al. (2010)</a> identified 51 pathogenic changes in the GNPTAB gene, including 42 novel mutations, among 61 probands mostly from the U.S. with ML II or ML III. Thirty-four probands, including 13 with ML II, 14 with ML III, and 7 with an intermediate phenotype, were studied in detail. Those with ML II had a more severe phenotype, with evidence of craniofacial and orthopedic problems at birth, severe psychomotor retardation, and enzyme activity of less than 1% of control values. Growth, speech, ambulation, and cognitive function were impaired. Those with ML III had enzyme activity of 1 to 10% of control values, minimal delays in milestones, and later onset of skeletal problems. ML II was associated with frameshift or truncating mutations, whereas ML III was associated with hypomorphic mutations. The most common mutation was 3503delTC (<a href="#0011">607840.0011</a>), found in 18 ML II and 4 ML III patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19617216" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 an N-ethyl-N-nitrosourea mutagenesis screen, <a href="#17" class="mim-tip-reference" title="Paton, L., Bitoun, E., Kenyon, J., Priestman, D. A., Oliver, P. L., Edwards, B., Platt, F. M., Davies, K. E. <strong>A novel mouse model of a patient mucolipidosis II mutation recapitulates disease pathology.</strong> J. Biol. Chem. 289: 26709-26721, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25107912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25107912</a>] [<a href="https://doi.org/10.1074/jbc.M114.586156" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25107912">Paton et al. (2014)</a> identified a line of mice with a novel mutation, termed Nymphe (nym), that caused growth retardation and ataxic gate. They identified the nym mutation as a c.2601T-A transversion in exon 13 of the Gnptab gene, resulting in a tyr867-to-ter (Y867X) substitution in the Gnptab preprotein prior to the cleavage signal between the alpha and beta subunits. The mutation resulted in a truncated alpha subunit, complete lack of the beta subunit, and retention of the alpha subunit in the endoplasmic reticulum. Whereas nym/+ mice appeared normal, nym/nym mutants had facial and skeletal abnormalities from birth, reduced fertility, progressive ataxia and motor incoordination, and elevated mortality. Nym/nym serum had abnormally high activity of lysosomal hydrolases, and tissues showed inclusion bodies indicative of lysosomal storage. Nym/nym brain showed atrophy, with progressive loss of cerebellar Purkinje cells. <a href="#17" class="mim-tip-reference" title="Paton, L., Bitoun, E., Kenyon, J., Priestman, D. A., Oliver, P. L., Edwards, B., Platt, F. M., Davies, K. E. <strong>A novel mouse model of a patient mucolipidosis II mutation recapitulates disease pathology.</strong> J. Biol. Chem. 289: 26709-26721, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25107912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25107912</a>] [<a href="https://doi.org/10.1074/jbc.M114.586156" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25107912">Paton et al. (2014)</a> concluded that the nym mutation produces a mouse model that recapitulates the human pathology of mucolipidosis II. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25107912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Barnes, T. D., Wozniak, D. F., Gutierrez, J., Han, T.-U., Drayna, D., Holy, T. E. <strong>A mutation associated with stuttering alters mouse pup ultrasonic vocalizations.</strong> Curr. Biol. 26: 1009-1018, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27151663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27151663</a>] [<a href="https://doi.org/10.1016/j.cub.2016.02.068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27151663">Barnes et al. (2016)</a> engineered mice to carry a homozygous glu1179-to-lys mutation in the Gnptab gene, which is homologous to the glu1200-to-lys mutation in human GNPTAB. Compared with wildtype pups, pups with the mutation emitted fewer vocalizations per unit time when separated from their dam. They also showed longer pauses between vocalizations and were more stereotyped in their vocalizations than wildtype littermates. Gnptab missense pups were similar to wildtype on an extensive battery of nonvocal behaviors. Speech from people who stutter showed similar abnormalities when compared with control speech. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27151663" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=607840[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs281865025 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865025;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs281865025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs281865025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a 47-year-old female who presented with dilated cardiomyopathy and mild neuropathy and was found to have mucolipidosis III (<a href="/entry/252600">252600</a>), <a href="#19" class="mim-tip-reference" title="Steet, R. A., Hullin, R., Kudo, M., Martinelli, M., Bosshard, N. U., Schaffner, T., Kornfeld, S. Steinmann, B. <strong>A splicing mutation in the alpha/beta GlcNAc-1-phosphotransferase gene results in an adult onset form of mucolipidosis III associated with sensory neuropathy and cardiomyopathy.</strong> Am. J. Med. Genet. 132A: 369-375, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15633164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15633164</a>] [<a href="https://doi.org/10.1002/ajmg.a.30498" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15633164">Steet et al. (2005)</a> identified a homozygous G-A transition in the last nucleotide of exon 7 of the GNPTAB gene, resulting in skipping of exon 7 and the production of a minimal amount of functional enzyme. The patient exhibited none of the connective tissue anomalies characteristic of mucolipidosis III, and the authors stated that this was the first example of the disease presenting in an adult patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15633164" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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>.0002 MUCOLIPIDOSIS III ALPHA/BETA</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">rs137852895 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852895;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852895" 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=RCV000002889" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002889" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002889</a>
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<p>In a 14-year-old boy with a mild clinical phenotype of mucolipidosis III (<a href="/entry/252600">252600</a>), <a href="#20" class="mim-tip-reference" title="Tiede, S., Muschol, N., Reutter, G., Cantz, M., Ullrich, K., Braulke, T. <strong>Missense mutations in N-acetylglucosamine-1-phosphotransferase alpha/beta subunit gene in a patient with mucolipidosis III and a mild clinical phenotype.</strong> Am. J. Med. Genet. 137A: 235-240, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16094673/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16094673</a>] [<a href="https://doi.org/10.1002/ajmg.a.30868" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16094673">Tiede et al. (2005)</a> identified homozygosity for a 1220A-C transversion in exon 10 of the GNPTAB gene, resulting in an asp407-to-ala (D407A) substitution. Both parents were heterozygous for the mutation, which was not found in 200 normal alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16094673" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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">rs137852896 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852896;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852896" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852896" 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=RCV000002890 OR RCV001380992" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002890, RCV001380992" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002890...</a>
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<p>In a 1-year-old Korean girl with mucolipidosis II (<a href="/entry/252500">252500</a>), <a href="#16" class="mim-tip-reference" title="Paik, K. H., Song, S. M., Ki, C. S., Yu, H.-W., Kim, J. S., Min, K. H., Chang, S. H., Yoo, E. J., Lee, I. J., Kwan, E. K., Han, S. J., Jin, D.-K. <strong>Identification of mutations in the GNPTA (MGC4170) gene coding for GlcNAc-phosphotransferase alpha/beta subunits in Korean patients with mucolipidosis type II or type IIIA.</strong> Hum. Mutat. 26: 308-314, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16116615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16116615</a>] [<a href="https://doi.org/10.1002/humu.20205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16116615">Paik et al. (2005)</a> identified compound heterozygosity for a 310C-T transition in exon 3 and a 3565C-T transition in exon 19 of the GNPTAB gene, resulting in a gln104-to-ter (Q104X) and an arg1189-to-ter (R1189X; <a href="#0004">607840.0004</a>) substitution, respectively. The patient had growth retardation, developmental delay, hypotonia, severe skeletal deformity with hip subluxation, gum hypertrophy, and severe mitral and aortic valve prolapse with regurgitation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16116615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 MUCOLIPIDOSIS II ALPHA/BETA</strong>
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MUCOLIPIDOSIS III ALPHA/BETA, INCLUDED
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852897 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852897;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/rs137852897?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=rs137852897" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852897" 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=RCV000002891 OR RCV000002892 OR RCV000664622 OR RCV000723447 OR RCV001193438 OR RCV003398424" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002891, RCV000002892, RCV000664622, RCV000723447, RCV001193438, RCV003398424" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002891...</a>
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<p>For discussion of the arg1189-to-ter (R1189X) mutation in the GNPTAB gene that was found in compound heterozygous state in a patient with mucolipidosis II (<a href="/entry/252500">252500</a>) by <a href="#16" class="mim-tip-reference" title="Paik, K. H., Song, S. M., Ki, C. S., Yu, H.-W., Kim, J. S., Min, K. H., Chang, S. H., Yoo, E. J., Lee, I. J., Kwan, E. K., Han, S. J., Jin, D.-K. <strong>Identification of mutations in the GNPTA (MGC4170) gene coding for GlcNAc-phosphotransferase alpha/beta subunits in Korean patients with mucolipidosis type II or type IIIA.</strong> Hum. Mutat. 26: 308-314, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16116615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16116615</a>] [<a href="https://doi.org/10.1002/humu.20205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16116615">Paik et al. (2005)</a>, see <a href="#0003">607840.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16116615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Otomo, T., Muramatsu, T., Yorifuji, T., Okuyama, T., Nakabayashi, H., Fukao, T., Ohura, T., Yoshino, M., Tanaka, A., Okamoto, N., Inui, K., Ozono, K., Sakai, N. <strong>Mucolipidosis II and III alpha/beta: mutation analysis of 40 Japanese patients showed genotype-phenotype correlation.</strong> J. Hum. Genet. 54: 145-151, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19197337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19197337</a>] [<a href="https://doi.org/10.1038/jhg.2009.3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19197337">Otomo et al. (2009)</a> identified a 3565C-T transition in the GNPTAB gene, resulting in an arg1189-to-ter (R1189X) substitution in 33 (41%) of 80 mutant GNPTAB alleles from 40 unrelated Japanese patients with mucolipidosis II or mucolipidosis III (<a href="/entry/252600">252600</a>). Patients with the more severe mucolipidosis II tended to have the R1189X mutation in homozygosity or in compound heterozygosity with a truncating mutation. None of the patients with the less severe mucolipidosis III carried R1189X in homozygosity; most were compound heterozygous for R1189X and F374L (<a href="#0015">607840.0015</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19197337" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0005" class="mim-anchor"></a>
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<strong>.0005 MUCOLIPIDOSIS II ALPHA/BETA</strong>
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GNPTAB, SER1058TER
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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> rs137852898 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852898;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/rs137852898?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=rs137852898" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852898" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002893" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002893" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002893</a>
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<p>In a 2-year-old Korean girl with mucolipidosis II (<a href="/entry/252500">252500</a>), <a href="#16" class="mim-tip-reference" title="Paik, K. H., Song, S. M., Ki, C. S., Yu, H.-W., Kim, J. S., Min, K. H., Chang, S. H., Yoo, E. J., Lee, I. J., Kwan, E. K., Han, S. J., Jin, D.-K. <strong>Identification of mutations in the GNPTA (MGC4170) gene coding for GlcNAc-phosphotransferase alpha/beta subunits in Korean patients with mucolipidosis type II or type IIIA.</strong> Hum. Mutat. 26: 308-314, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16116615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16116615</a>] [<a href="https://doi.org/10.1002/humu.20205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16116615">Paik et al. (2005)</a> identified compound heterozygosity for a 3173C-G transversion in exon 16 and a 2-bp deletion (3474delTA) in exon 19 of the GNPTAB gene, resulting in a ser1058-to-ter (S1058X) substitution and a frameshift leading to premature termination (<a href="#0006">607840.0006</a>), respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16116615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<span class="mim-font">
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<strong>.0006 MUCOLIPIDOSIS II ALPHA/BETA</strong>
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GNPTAB, 2-BP DEL, 3474TA
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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> rs281865038 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865038;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/rs281865038?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=rs281865038" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs281865038" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002894" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002894" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002894</a>
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<p>For discussion of the 2-bp deletion in the GNPTAB gene (3474delTA) that was found in compound heterozygous state in a patient with mucolipidosis II (<a href="/entry/252500">252500</a>) by <a href="#16" class="mim-tip-reference" title="Paik, K. H., Song, S. M., Ki, C. S., Yu, H.-W., Kim, J. S., Min, K. H., Chang, S. H., Yoo, E. J., Lee, I. J., Kwan, E. K., Han, S. J., Jin, D.-K. <strong>Identification of mutations in the GNPTA (MGC4170) gene coding for GlcNAc-phosphotransferase alpha/beta subunits in Korean patients with mucolipidosis type II or type IIIA.</strong> Hum. Mutat. 26: 308-314, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16116615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16116615</a>] [<a href="https://doi.org/10.1002/humu.20205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16116615">Paik et al. (2005)</a>, see <a href="#0005">607840.0005</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16116615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0007" class="mim-anchor"></a>
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<strong>.0007 MUCOLIPIDOSIS II ALPHA/BETA</strong>
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GNPTAB, TRP894TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852899 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852899;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852899" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852899" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002895" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002895" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002895</a>
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<p>In a 1-year-old Korean girl with mucolipidosis II (<a href="/entry/252500">252500</a>), <a href="#16" class="mim-tip-reference" title="Paik, K. H., Song, S. M., Ki, C. S., Yu, H.-W., Kim, J. S., Min, K. H., Chang, S. H., Yoo, E. J., Lee, I. J., Kwan, E. K., Han, S. J., Jin, D.-K. <strong>Identification of mutations in the GNPTA (MGC4170) gene coding for GlcNAc-phosphotransferase alpha/beta subunits in Korean patients with mucolipidosis type II or type IIIA.</strong> Hum. Mutat. 26: 308-314, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16116615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16116615</a>] [<a href="https://doi.org/10.1002/humu.20205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16116615">Paik et al. (2005)</a> identified compound heterozygosity for a 2681G-A transition in exon 13 of the GNPTAB gene resulting in a trp894-to-ter (W894X) substitution and an R1189X mutation (<a href="#0004">607840.0004</a>). The patient had growth retardation, developmental delay, gum hypertrophy, joint restriction, coxa valga, and coronary artery atresia requiring coronary artery bypass surgery. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16116615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0008" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0008 MUCOLIPIDOSIS III ALPHA/BETA</strong>
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GNPTAB, IVS13, G-A, +1
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs281865031 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865031;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/rs281865031?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=rs281865031" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs281865031" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000031976 OR RCV000664616 OR RCV001193439 OR RCV001274138 OR RCV001293695 OR RCV001572905 OR RCV004528068" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000031976, RCV000664616, RCV001193439, RCV001274138, RCV001293695, RCV001572905, RCV004528068" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000031976...</a>
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<p>In 2 Korean girls with mucolipidosis IIIA (<a href="/entry/252600">252600</a>), <a href="#16" class="mim-tip-reference" title="Paik, K. H., Song, S. M., Ki, C. S., Yu, H.-W., Kim, J. S., Min, K. H., Chang, S. H., Yoo, E. J., Lee, I. J., Kwan, E. K., Han, S. J., Jin, D.-K. <strong>Identification of mutations in the GNPTA (MGC4170) gene coding for GlcNAc-phosphotransferase alpha/beta subunits in Korean patients with mucolipidosis type II or type IIIA.</strong> Hum. Mutat. 26: 308-314, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16116615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16116615</a>] [<a href="https://doi.org/10.1002/humu.20205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16116615">Paik et al. (2005)</a> identified compound heterozygosity for a splice site mutation, a 2715+1G-A transition in intron 13 of the GNPTAB gene, with an R1189X mutation (<a href="#0004">607840.0004</a>) and a 2-bp deletion (2574delGA) in exon 13 (<a href="#0009">607840.0009</a>), respectively. The 2574delGA mutation results in premature termination. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16116615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs281865029 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865029;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/rs281865029?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=rs281865029" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs281865029" 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=RCV000031974 OR RCV000671157" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000031974, RCV000671157" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000031974...</a>
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<p>For discussion of the 2-bp deletion in the GNPTAB gene (2574delGA) that was found in compound heterozygous state in patients with mucolipidosis IIIA (<a href="/entry/252600">252600</a>) by <a href="#16" class="mim-tip-reference" title="Paik, K. H., Song, S. M., Ki, C. S., Yu, H.-W., Kim, J. S., Min, K. H., Chang, S. H., Yoo, E. J., Lee, I. J., Kwan, E. K., Han, S. J., Jin, D.-K. <strong>Identification of mutations in the GNPTA (MGC4170) gene coding for GlcNAc-phosphotransferase alpha/beta subunits in Korean patients with mucolipidosis type II or type IIIA.</strong> Hum. Mutat. 26: 308-314, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16116615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16116615</a>] [<a href="https://doi.org/10.1002/humu.20205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16116615">Paik et al. (2005)</a>, see <a href="#0008">607840.0008</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16116615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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">rs281865027 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865027;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs281865027" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs281865027" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a patient with mucolipidosis II (<a href="/entry/252500">252500</a>), <a href="#21" class="mim-tip-reference" title="Tiede, S., Storch, S., Lubke, T., Henrissat, B., Bargal, R., Raas-Rothschild, A., Braulke, T. <strong>Mucolipidosis II is caused by mutations in GNPTA encoding the alpha/beta GlcNAc-1-phosphotransferase.</strong> Nature Med. 11: 1109-1112, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16200072/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16200072</a>] [<a href="https://doi.org/10.1038/nm1305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16200072">Tiede et al. (2005)</a> identified homozygosity for a 1-bp insertion in exon 13 of the GNPTAB gene, resulting in a premature termination directly after the putative second Notch repeat-like domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16200072" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs34002892 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs34002892;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/rs34002892?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=rs34002892" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs34002892" 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=RCV000002899 OR RCV000002900 OR RCV000082192 OR RCV000623507 OR RCV000678389 OR RCV004528069" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002899, RCV000002900, RCV000082192, RCV000623507, RCV000678389, RCV004528069" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002899...</a>
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<p>In 8 of 9 pedigrees with mucolipidosis II (<a href="/entry/252500">252500</a>) and 5 of 7 with mucolipidosis IIIA (<a href="/entry/252600">252600</a>), <a href="#12" class="mim-tip-reference" title="Kudo, M., Brem, M. S., Canfield, W. M. <strong>Mucolipidosis II (I-cell disease) and mucolipidosis IIIA (classical pseudo-Hurler polydystrophy) are caused by mutations in the GlcNAc-phosphotransferase alpha/beta-subunits precursor gene.</strong> Am. J. Hum. Genet. 78: 451-463, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16465621/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16465621</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16465621[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/500849" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16465621">Kudo et al. (2006)</a> identified a frameshift mutation in the GNPTAB gene consisting of deletion of 2 nucleotides (3665_3666delTC based on numbering of the first base in the initiation codon of a BAC clone) beginning at leu1168 and leading to premature termination at amino acid 1172 (Leu1168fsTer1172). This mutation was the most frequent in their study and was found in both the homozygous and compound heterozygous state, in combination with severe mutations (i.e., mutations preventing the generation of active enzyme) in ML II and with mild mutations (i.e., mutations allowing the generation of active enzyme) in ML IIIA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16465621" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 27 parents of 16 deceased French Canadian children with mucolipidosis II alpha/beta, <a href="#18" class="mim-tip-reference" title="Plante, M., Claveau, S., Lepage, P., Lavoie, E.-M., Brunet, S., Roquis, D., Morin, C., Vezina, H., Laprise, C. <strong>Mucolipidosis II: a single causal mutation in the N-acetylglucosamine-1-phosphotransferase gene (GNPTAB) in a French Canadian founder population.</strong> Clin. Genet. 73: 236-244, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18190596/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18190596</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00954.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18190596">Plante et al. (2008)</a> identified the 2-bp deletion (which they referred to as 3503_3504delTC based on numbering of the first nucleotide of the start codon as +1; <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs34002892;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs34002892</a>) in exon 19 of the GNPTAB gene, resulting in a frameshift and premature termination. All parents carried the mutation in the heterozygous state, indicating that the children were likely homozygous. Genealogic data showed 6 founders (3 couples) with a high probability of having introduced the mutation in the population; all originated from France and were married in the Quebec region in the second half of the 17th century. <a href="#18" class="mim-tip-reference" title="Plante, M., Claveau, S., Lepage, P., Lavoie, E.-M., Brunet, S., Roquis, D., Morin, C., Vezina, H., Laprise, C. <strong>Mucolipidosis II: a single causal mutation in the N-acetylglucosamine-1-phosphotransferase gene (GNPTAB) in a French Canadian founder population.</strong> Clin. Genet. 73: 236-244, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18190596/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18190596</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00954.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18190596">Plante et al. (2008)</a> noted that the carrier rate of mucolipidosis II is estimated to be 1 in 39 in the Saguenay-Lac-Saint-Jean region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18190596" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Encarnacao, M., Lacerda, L., Costa, R., Prata, M. J., Coutinho, M. F., Ribeiro, H., Lopes, L., Pineda, M., Ignatius, J., Galvez, H., Mustonen, A., Vieira, P., Lima, M. R., Alves, S. <strong>Molecular analysis of the GNPTAB and GNPTG genes in 13 patients with mucolipidosis type II or type III - identification of eight novel mutations.</strong> Clin. Genet. 76: 76-84, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19659762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19659762</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2009.01185.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19659762">Encarnacao et al. (2009)</a> identified GNPTAB mutations in 9 mostly Portuguese patients with ML II. Eight of 9 patients had a nonsense or frameshift mutation, the most common being the 2-bp deletion (3503delTC) that was found in 45% of the mutant alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19659762" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By haplotype analysis of 44 carriers of the 3503delTC mutation from various populations, <a href="#7" class="mim-tip-reference" title="Coutinho, M. F., Encarnacao, M., Gomes, R., da Silva Santos, L., Martins, S., Sirois-Gagnon, D., Bargal, R., Filocamo, M., Raas-Rothschild, A., Tappino, B., Laprise, C., Cury, G. K., Schwartz, I. V., Artigalas, O., Prata, M. J., Alves, S. <strong>Origin and spread of a common deletion causing mucolipidosis type II: insights from patterns of haplotypic diversity.</strong> Clin. Genet. 80: 273-280, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20880125/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20880125</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2010.01539.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20880125">Coutinho et al. (2011)</a> found that 59 (97%) of 61 mutant chromosomes shared a common haplotype covering 4 of the 5 polymorphic markers analyzed, indicating a strong founder effect. The 2 remaining chromosomes, both from Italian patients, differed by alleles only at 1 marker. A common haplotype encompassing the 3503delTC mutation was shared by individuals of Italian, Arab-Muslim, Turkish, Argentinian, Brazilian, Irish Traveller, Portuguese, and Canadian origin. The mutation was estimated to have occurred about 2,063 years ago, most likely in a peri-Mediterranean region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20880125" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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> rs34940801 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs34940801;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/rs34940801?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=rs34940801" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs34940801" 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=RCV000002901 OR RCV001328325 OR RCV001381208 OR RCV001781170" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002901, RCV001328325, RCV001381208, RCV001781170" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002901...</a>
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<p>In a patient with type II mucolipidosis (<a href="/entry/252500">252500</a>), <a href="#12" class="mim-tip-reference" title="Kudo, M., Brem, M. S., Canfield, W. M. <strong>Mucolipidosis II (I-cell disease) and mucolipidosis IIIA (classical pseudo-Hurler polydystrophy) are caused by mutations in the GlcNAc-phosphotransferase alpha/beta-subunits precursor gene.</strong> Am. J. Hum. Genet. 78: 451-463, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16465621/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16465621</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16465621[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/500849" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16465621">Kudo et al. (2006)</a> described a splice site mutation in the GNPTAB gene, IVS17+1G-A, that was predicted to cause skipping of exon 17 and a frameshift beginning at pro1084 and ending with premature termination at residue 1085 (P1084fsX1085). This mutation was found in compound heterozygosity with the FS1172 mutation (<a href="#0011">607840.0011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16465621" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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 MUCOLIPIDOSIS III ALPHA/BETA</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> rs34788341 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs34788341;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/rs34788341?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=rs34788341" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs34788341" 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=RCV000002902 OR RCV000031982 OR RCV000032336 OR RCV000665095 OR RCV001781171" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002902, RCV000031982, RCV000032336, RCV000665095, RCV001781171" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002902...</a>
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<p>In a family with 2 affected sibs and in 2 patients with mucolipidosis IIIA (<a href="/entry/252900">252900</a>), <a href="#12" class="mim-tip-reference" title="Kudo, M., Brem, M. S., Canfield, W. M. <strong>Mucolipidosis II (I-cell disease) and mucolipidosis IIIA (classical pseudo-Hurler polydystrophy) are caused by mutations in the GlcNAc-phosphotransferase alpha/beta-subunits precursor gene.</strong> Am. J. Hum. Genet. 78: 451-463, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16465621/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16465621</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16465621[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/500849" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16465621">Kudo et al. (2006)</a> described a donor splice site mutation in intron 17 of the GNPTAB gene, IVS17+6T-G, that results in skipping of exon 17 and a frameshift with a premature termination at residue 1085 (Pro1084fsTer1172). This same result was observed in another intron 17 splice site mutation in a patient with ML II (<a href="#0012">607840.0012</a>). The former intron 17 splice site mutation was designated type I and the latter type II. Although the mRNA sequences derived from these 2 mutations are the same, the GlcNAc-phosphotransferase activities and clinical outcomes are different; fibroblasts with the type I mutation exhibited less than 0.1% activity, whereas those carrying the type II mutation exhibited 1 to 3% GlcNAc-phosphotransferase activity. That the type II mutation was located outside the invariant splice site was suggested as a possible cause of the greater activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16465621" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<span class="mim-font">
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<strong>.0014 MUCOLIPIDOSIS III ALPHA/BETA</strong>
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GNPTAB, LYS4GLN
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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> rs34159654 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs34159654;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/rs34159654?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=rs34159654" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs34159654" 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=RCV000002903 OR RCV000031965 OR RCV000669013" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002903, RCV000031965, RCV000669013" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002903...</a>
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<p>In a family and a unrelated single patient with mucolipidosis IIIA (<a href="/entry/252900">252900</a>), <a href="#12" class="mim-tip-reference" title="Kudo, M., Brem, M. S., Canfield, W. M. <strong>Mucolipidosis II (I-cell disease) and mucolipidosis IIIA (classical pseudo-Hurler polydystrophy) are caused by mutations in the GlcNAc-phosphotransferase alpha/beta-subunits precursor gene.</strong> Am. J. Hum. Genet. 78: 451-463, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16465621/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16465621</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16465621[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/500849" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16465621">Kudo et al. (2006)</a> identified an A-to-C transversion in exon 1 of the GNPTAB gene, resulting in a lys4-to-gln (K4Q) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16465621" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0015" class="mim-anchor"></a>
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<strong>.0015 MUCOLIPIDOSIS III ALPHA/BETA</strong>
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MUCOLIPIDOSIS II ALPHA/BETA, INCLUDED
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GNPTAB, PHE374LEU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852900 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852900;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852900" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852900" 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=RCV000002904 OR RCV000002905" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002904, RCV000002905" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002904...</a>
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<p><a href="#15" class="mim-tip-reference" title="Otomo, T., Muramatsu, T., Yorifuji, T., Okuyama, T., Nakabayashi, H., Fukao, T., Ohura, T., Yoshino, M., Tanaka, A., Okamoto, N., Inui, K., Ozono, K., Sakai, N. <strong>Mucolipidosis II and III alpha/beta: mutation analysis of 40 Japanese patients showed genotype-phenotype correlation.</strong> J. Hum. Genet. 54: 145-151, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19197337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19197337</a>] [<a href="https://doi.org/10.1038/jhg.2009.3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19197337">Otomo et al. (2009)</a> identified a 1120T-C transition in exon 10 of the GNPTAB gene, resulting in a phe374-to-leu (F374L) substitution in 7 of 15 unrelated Japanese patients with mucolipidosis III (<a href="/entry/252600">252600</a>). Most were in compound heterozygosity with R1189X (<a href="#0004">607840.0004</a>). Only 1 of 25 patients with a diagnosis of the more severe mucolipidosis II (<a href="/entry/252500">252500</a>) carried the F374L mutation; the second mutant allele in this patient was not identified. However, <a href="#15" class="mim-tip-reference" title="Otomo, T., Muramatsu, T., Yorifuji, T., Okuyama, T., Nakabayashi, H., Fukao, T., Ohura, T., Yoshino, M., Tanaka, A., Okamoto, N., Inui, K., Ozono, K., Sakai, N. <strong>Mucolipidosis II and III alpha/beta: mutation analysis of 40 Japanese patients showed genotype-phenotype correlation.</strong> J. Hum. Genet. 54: 145-151, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19197337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19197337</a>] [<a href="https://doi.org/10.1038/jhg.2009.3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19197337">Otomo et al. (2009)</a> stated that this patient had a relatively attenuated course, suggesting that F374L is associated with milder clinical manifestations. The F374L mutation occurred in 8 (10%) of 80 mutant alleles. Analysis of surrounding polymorphisms suggested a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19197337" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-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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Bao, M., Booth, J. L., Elmendorf, B. J., Canfield, W. M.
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<strong>Bovine UDP-N-acetylglucosamine:lysosomal-enzyme N-acetylglucosamine-1-phosphotransferase: I. Purification and subunit structure.</strong>
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J. Biol. Chem. 271: 31437-31445, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8940155/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8940155</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8940155" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.271.49.31437" target="_blank">Full Text</a>]
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Bao, M., Elmendorf, B. J., Booth, J. L., Drake, R. R., Canfield, W. M.
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<strong>Bovine UDP-N-acetylglucosamine:lysosomal-enzyme N-acetylglucosamine-1-phosphotransferase: II. Enzymatic characterization and identification of the catalytic subunit.</strong>
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J. Biol. Chem. 271: 31446-31451, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8940156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8940156</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8940156" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.271.49.31446" target="_blank">Full Text</a>]
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Bargal, R., Zeigler, M., Abu-Libdeh, B., Zuri, V., Mandel, H., Neriah, Z. B., Stewart, F., Elcioglu, N., Hindi, T., Le Merrer, M., Bach, G., Raas-Rothschild, A.
|
|
<strong>When mucolipidosis III meets mucolipidosis II: GNPTA gene mutations in 24 patients.</strong>
|
|
Molec. Genet. Metab. 88: 359-363, 2006. Note: Erratum: Molec. Genet. Metab. 91: 299 only, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16630736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16630736</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16630736" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.ymgme.2006.03.003" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Barnes2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Barnes, T. D., Wozniak, D. F., Gutierrez, J., Han, T.-U., Drayna, D., Holy, T. E.
|
|
<strong>A mutation associated with stuttering alters mouse pup ultrasonic vocalizations.</strong>
|
|
Curr. Biol. 26: 1009-1018, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27151663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27151663</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27151663" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.cub.2016.02.068" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Canfield1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Canfield, W. M., Bao, M., Pan, J., Brewer, A. D. K., Pan, H., Roe, B., Raas-Rothschild, A.
|
|
<strong>Mucolipidosis II and mucolipidosis IIIA are caused by mutations in the GlcNAc-phosphotransferase alpha/beta gene on chromosome 12p. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 63: A15 only, 1998.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Cathey2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cathey, S. S., Leroy, J. G., Wood, T., Eaves, K., Simensen, R. J., Kudo, M., Stevenson, R. E., Friez, M. J.
|
|
<strong>Phenotype and genotype in mucolipidoses II and III alpha/beta: a study of 61 probands.</strong>
|
|
J. Med. Genet. 47: 38-48, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19617216/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19617216</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19617216[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=19617216" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2009.067736" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Coutinho2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Coutinho, M. F., Encarnacao, M., Gomes, R., da Silva Santos, L., Martins, S., Sirois-Gagnon, D., Bargal, R., Filocamo, M., Raas-Rothschild, A., Tappino, B., Laprise, C., Cury, G. K., Schwartz, I. V., Artigalas, O., Prata, M. J., Alves, S.
|
|
<strong>Origin and spread of a common deletion causing mucolipidosis type II: insights from patterns of haplotypic diversity.</strong>
|
|
Clin. Genet. 80: 273-280, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20880125/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20880125</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20880125" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.2010.01539.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Encarnacao2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Encarnacao, M., Lacerda, L., Costa, R., Prata, M. J., Coutinho, M. F., Ribeiro, H., Lopes, L., Pineda, M., Ignatius, J., Galvez, H., Mustonen, A., Vieira, P., Lima, M. R., Alves, S.
|
|
<strong>Molecular analysis of the GNPTAB and GNPTG genes in 13 patients with mucolipidosis type II or type III - identification of eight novel mutations.</strong>
|
|
Clin. Genet. 76: 76-84, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19659762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19659762</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19659762" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.2009.01185.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Fedyna2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fedyna, A., Drayna, D., Kang, C.
|
|
<strong>Characterization of a mutation commonly associated with persistent stuttering: evidence for a founder mutation.</strong>
|
|
J. Hum. Genet. 56: 80-82, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20944643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20944643</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20944643[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=20944643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/jhg.2010.125" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Kang2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kang, C., Riazuddin, S., Mundorff, J., Krasnewich, D., Friedman, P., Mullikin, J. C., Drayna, D.
|
|
<strong>Mutations in the lysosomal enzyme-targeting pathway and persistent stuttering.</strong>
|
|
New Eng. J. Med. 362: 677-685, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20147709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20147709</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20147709[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=20147709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMoa0902630" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Kudo2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kudo, M., Bao, M., D'Souza, A., Ying, F., Pan, H., Roe, B. A., Canfield, W. M.
|
|
<strong>The alpha- and beta-subunits of the human UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase are encoded by a single cDNA.</strong>
|
|
J. Biol. Chem. 280: 36141-36149, 2005. Note: Erratum: J. Biol. Chem. 280: 42476 only, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16120602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16120602</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16120602" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M509008200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Kudo2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kudo, M., Brem, M. S., Canfield, W. M.
|
|
<strong>Mucolipidosis II (I-cell disease) and mucolipidosis IIIA (classical pseudo-Hurler polydystrophy) are caused by mutations in the GlcNAc-phosphotransferase alpha/beta-subunits precursor gene.</strong>
|
|
Am. J. Hum. Genet. 78: 451-463, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16465621/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16465621</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16465621[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=16465621" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/500849" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Marschner2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Marschner, K., Kollmann, K., Schweizer, M., Braulke, T., Pohl, S.
|
|
<strong>A key enzyme in the biogenesis of lysosomes is a protease that regulates cholesterol metabolism.</strong>
|
|
Science 333: 87-90, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21719679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21719679</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21719679" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1205677" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Mueller1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mueller, O. T., Wasmuth, J. J., Murray, J. C., Lozzio, C. B., Lovrien, E. W., Shows, T. B.
|
|
<strong>Chromosomal assignment of N-acetylglucosaminylphosphotransferase, the lysosomal hydrolase targeting enzyme deficient in mucolipidosis II and III. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 46: 664, 1987.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Otomo2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Otomo, T., Muramatsu, T., Yorifuji, T., Okuyama, T., Nakabayashi, H., Fukao, T., Ohura, T., Yoshino, M., Tanaka, A., Okamoto, N., Inui, K., Ozono, K., Sakai, N.
|
|
<strong>Mucolipidosis II and III alpha/beta: mutation analysis of 40 Japanese patients showed genotype-phenotype correlation.</strong>
|
|
J. Hum. Genet. 54: 145-151, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19197337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19197337</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19197337" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/jhg.2009.3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Paik2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Paik, K. H., Song, S. M., Ki, C. S., Yu, H.-W., Kim, J. S., Min, K. H., Chang, S. H., Yoo, E. J., Lee, I. J., Kwan, E. K., Han, S. J., Jin, D.-K.
|
|
<strong>Identification of mutations in the GNPTA (MGC4170) gene coding for GlcNAc-phosphotransferase alpha/beta subunits in Korean patients with mucolipidosis type II or type IIIA.</strong>
|
|
Hum. Mutat. 26: 308-314, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16116615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16116615</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16116615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.20205" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Paton2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Paton, L., Bitoun, E., Kenyon, J., Priestman, D. A., Oliver, P. L., Edwards, B., Platt, F. M., Davies, K. E.
|
|
<strong>A novel mouse model of a patient mucolipidosis II mutation recapitulates disease pathology.</strong>
|
|
J. Biol. Chem. 289: 26709-26721, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25107912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25107912</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25107912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M114.586156" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Plante2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Plante, M., Claveau, S., Lepage, P., Lavoie, E.-M., Brunet, S., Roquis, D., Morin, C., Vezina, H., Laprise, C.
|
|
<strong>Mucolipidosis II: a single causal mutation in the N-acetylglucosamine-1-phosphotransferase gene (GNPTAB) in a French Canadian founder population.</strong>
|
|
Clin. Genet. 73: 236-244, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18190596/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18190596</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18190596" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.2007.00954.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Steet2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Steet, R. A., Hullin, R., Kudo, M., Martinelli, M., Bosshard, N. U., Schaffner, T., Kornfeld, S. Steinmann, B.
|
|
<strong>A splicing mutation in the alpha/beta GlcNAc-1-phosphotransferase gene results in an adult onset form of mucolipidosis III associated with sensory neuropathy and cardiomyopathy.</strong>
|
|
Am. J. Med. Genet. 132A: 369-375, 2005.
|
|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15633164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15633164</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15633164" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.30498" target="_blank">Full Text</a>]
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<a id="20" class="mim-anchor"></a>
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<a id="Tiede2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tiede, S., Muschol, N., Reutter, G., Cantz, M., Ullrich, K., Braulke, T.
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<strong>Missense mutations in N-acetylglucosamine-1-phosphotransferase alpha/beta subunit gene in a patient with mucolipidosis III and a mild clinical phenotype.</strong>
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Am. J. Med. Genet. 137A: 235-240, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16094673/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16094673</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16094673" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.30868" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="21" class="mim-anchor"></a>
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<a id="Tiede2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tiede, S., Storch, S., Lubke, T., Henrissat, B., Bargal, R., Raas-Rothschild, A., Braulke, T.
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<strong>Mucolipidosis II is caused by mutations in GNPTA encoding the alpha/beta GlcNAc-1-phosphotransferase.</strong>
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Nature Med. 11: 1109-1112, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16200072/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16200072</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16200072" 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/nm1305" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="22" class="mim-anchor"></a>
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<a id="Vidgoff1982" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Vidgoff, J., Rowe, S., Stafford, R., Buist, N. R. M., Lovrien, E. W.
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<strong>Localization of the gene for I-cell disease (mucolipidosis II). (Abstract)</strong>
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Am. J. Hum. Genet. 34: 64A, 1982.
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Patricia A. Hartz - updated : 03/07/2018
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Patricia A. Hartz - updated : 07/19/2016<br>Cassandra L. Kniffin - updated : 10/4/2011<br>Ada Hamosh - updated : 9/1/2011<br>Cassandra L. Kniffin - updated : 2/14/2011<br>Cassandra L. Kniffin - updated : 6/15/2010<br>Cassandra L. Kniffin - updated : 5/25/2010<br>Cassandra L. Kniffin - updated : 3/8/2010<br>Cassandra L. Kniffin - updated : 5/27/2009<br>Cassandra L. Kniffin - updated : 5/6/2008<br>Cassandra L. Kniffin - updated : 3/13/2008<br>Ada Hamosh - updated : 6/28/2007<br>Victor A. McKusick - updated : 2/21/2006<br>Marla J. F. O'Neill - updated : 10/26/2005<br>Marla J. F. O'Neill - updated : 10/3/2005<br>Marla J. F. O'Neill - updated : 3/1/2005
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<a id="creationDate" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 5/30/2003
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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mgross : 03/07/2018
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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mgross : 03/07/2018<br>carol : 12/15/2017<br>joanna : 07/20/2016<br>alopez : 07/19/2016<br>carol : 08/17/2015<br>carol : 4/7/2015<br>mcolton : 4/6/2015<br>terry : 8/31/2012<br>carol : 10/27/2011<br>terry : 10/26/2011<br>carol : 10/11/2011<br>ckniffin : 10/4/2011<br>alopez : 9/6/2011<br>terry : 9/1/2011<br>terry : 3/10/2011<br>terry : 3/10/2011<br>wwang : 3/2/2011<br>ckniffin : 2/14/2011<br>wwang : 6/25/2010<br>ckniffin : 6/15/2010<br>wwang : 6/1/2010<br>ckniffin : 5/25/2010<br>ckniffin : 5/25/2010<br>wwang : 3/8/2010<br>ckniffin : 3/8/2010<br>wwang : 6/3/2009<br>ckniffin : 5/27/2009<br>wwang : 5/12/2008<br>ckniffin : 5/6/2008<br>wwang : 3/13/2008<br>alopez : 7/6/2007<br>terry : 6/28/2007<br>alopez : 3/8/2006<br>terry : 2/21/2006<br>wwang : 10/31/2005<br>terry : 10/26/2005<br>wwang : 10/10/2005<br>wwang : 10/7/2005<br>terry : 10/3/2005<br>carol : 3/30/2005<br>wwang : 3/7/2005<br>terry : 3/1/2005<br>carol : 5/30/2003
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<h3>
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<span class="mim-font">
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<strong>*</strong> 607840
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<div>
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<h3>
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<span class="mim-font">
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N-ACETYLGLUCOSAMINE-1-PHOSPHOTRANSFERASE, ALPHA/BETA SUBUNITS; GNPTAB
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</span>
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</h3>
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</div>
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<br />
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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GNPTA<br />
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MGC4170
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: GNPTAB</em></strong>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 65764006;
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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: 12q23.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 12:101,745,499-101,830,959 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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<tbody>
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<td rowspan="2">
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<span class="mim-font">
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12q23.2
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<td>
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<span class="mim-font">
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Mucolipidosis II alpha/beta
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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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252500
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<td>
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<span class="mim-font">
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Autosomal recessive
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</td>
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<td>
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<span class="mim-font">
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3
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<span class="mim-font">
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Mucolipidosis III alpha/beta
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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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252600
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>UDP-N-acetylglucosamine:lysosomal-enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase; EC 2.7.8.17) catalyzes the initial step in the synthesis of the mannose 6-phosphate determinant required for efficient intracellular targeting of newly synthesized lysosomal hydrolases to the lysosome. GlcNAc-phosphotransferase is an alpha-2/beta-2/gamma-2 hexameric complex. The GNPTAB gene encodes both the alpha and beta subunits; the gamma subunit is encoded by the GNPTG gene (607838).</p>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Bao et al. (1996, 1996) determined that bovine GlcNAc-phosphotransferase is a 54-kD alpha-2/beta-2/gamma-2 hexameric complex. Canfield et al. (1998) indicated that the alpha and beta subunits are derived from a single cDNA. The individual subunits are apparently generated by proteolytic processing at a lys-asp bond following synthesis of an alpha/beta precursor, generating a 928-amino acid N-terminal alpha subunit and a 328-amino acid C-terminal beta subunit. The gamma subunit is encoded by a separate gene (GNPTG; 607838). </p><p>By database analysis, Tiede et al. (2005) identified the human GNPTAB gene. The deduced 1256-amino acid protein has a predicted molecular mass of 144 kD. Hydrophobicity analysis showed 2 transmembrane domains and 19 potential N-glycosylation sites. Sequence comparisons showed that GNPTAB has a complex modular structure composed of at least 6 domains including an N-terminal domain with a putative nucleotide binding site, 2 Notch repeat-like domains, and a DMAP1 (605077) binding-like domain. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By database analysis, Tiede et al. (2005) determined that the GNPTAB gene contains 21 exons and spans 85 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>Vidgoff et al. (1982) found possible linkage of ML II to MN (111300) on 4q, with a lod score of 1.3. Mueller et al. (1987) determined the chromosome assignment of the structural gene altered in the common forms of ML II and ML III by linkage analysis, somatic cell hybrids, and gene dosage. Linkage data with ML II families indicated that the ML II locus is located between GC (139200) and MNS. The combined data indicated that GNPTA maps to 4q21-q23.</p><p>By genomic sequence analysis, Tiede et al. (2005) mapped the GNPTAB gene to chromosome 12q23.3. </p><p>Paton et al. (2014) stated that the mouse Gnptab gene maps to chromosome 10. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Canfield et al. (1998) found that in 4 of 4 patients with mucolipidosis II (ML II; 252500), the 6.2-kb alpha/beta transcript was absent. In 2 of 2 patients with mucolipidosis IIIA (252600), the alpha/beta transcript was present but greatly reduced. In all patients examined, the gamma transcript was present at normal levels.</p><p>By retroviral transduction of fibroblasts from an individual with mucolipidosis II, Tiede et al. (2005) demonstrated expression and localization of GNPTAB in the Golgi apparatus, accompanied by correction of the hypersecretion of lysosomal enzymes. Tiede et al. (2005) concluded that GNPTAB encodes a subunit of GlcNAc-phosphotransferase that is defective in individuals with ML II. </p><p>Kudo et al. (2005) cloned the cDNA and genomic DNA encoding the alpha/beta-subunits precursor gene (GNPTAB). With the cloning of the gamma-subunit gene (GNPTG; 607838), it could be concluded that GlcNAc-phosphotransferase is the product of 2 genes, an uncommon exception to the Garrod-Beadle principle of 1 enzyme-1 gene. </p><p>Marschner et al. (2011) found that the alpha/beta subunit of the N-acetylglucosamine-1-phosphotransferase complex is cleaved by the site-1 protease (S1P; 603355) that activates sterol regulatory element-binding proteins in response to cholesterol deprivation. S1P-deficient cells failed to activate the alpha/beta subunit precursor and exhibited a mucolipidosis II-like phenotype. Thus, Marschner et al. (2011) concluded that S1P functions in the biogenesis of lysosomes, and that lipid-independent phenotypes of S1P deficiency may be caused by lysosomal dysfunction. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In a 47-year-old female who presented with dilated cardiomyopathy and mild neuropathy and was found to have mucolipidosis III (252600), Steet et al. (2005) identified a homozygous splice site mutation of the GNPTAB gene (607840.0001). </p><p>In a 14-year-old boy with a mild clinical phenotype of mucolipidosis III, Tiede et al. (2005) identified homozygosity for an asp407-to-ala substitution in the GNPTAB gene (607840.0002). The patient was also homozygous for an ala663-to-gly substitution in the GNPTAB that was deemed a polymorphism because it was found in 5% of normal alleles. Both parents were heterozygous for both mutations. </p><p>In 3 unrelated Korean girls with mucolipidosis II (252500) and 2 unrelated Korean girls with mucolipidosis IIIA, Paik et al. (2005) identified compound heterozygosity for 7 different mutations in the GNPTAB gene (607840.0003-607840.0009). </p><p>In 6 patients with clinically and biochemically diagnosed mucolipidosis II, Tiede et al. (2005) identified homozygosity or compound heterozygosity for 7 mutations in the GNPTAB gene, all resulting in premature translational termination (e.g., 607840.0010). </p><p>To determine whether mucolipidosis II, or I-cell disease, and mucolipidosis IIIA, or classic pseudo-Hurler polydystrophy, are caused by mutations in the gene encoding the alpha/beta-subunits precursor gene, Kudo et al. (2006) sequenced GNPTAB exons and flanking intronic sequences and measured GlcNAc-phosphotransferase activity in patient fibroblasts. They identified 15 different mutations in GNPTAB from 18 pedigrees with one or the other of these 2 diseases and demonstrated that these 2 diseases are allelic. Mutations in both alleles were identified in each case, which demonstrated that GNPTAB mutations are the cause of both diseases. Some pedigrees had identical mutations. A 2-bp deletion (607840.0011), resulting in a frameshift and premature termination, predominated and was found in both ML II and ML IIIA. This mutation was found in combination with severe mutations (i.e., mutations preventing the generation of active enzyme) in ML II and with mild mutations (i.e., mutations allowing the generation of active enzyme) in ML IIIA. Some cases of ML II and ML IIIA were the result of mutations that cause aberrant splicing. Substitutions were within the invariant splice site sequence in ML II and were outside it in ML IIIA. When the mutations were analyzed along with GlcNAc-phosphotransferase activity, it was possible to distinguish with confidence these 2 related but distinct disorders. </p><p>Bargal et al. (2006) studied GNPTAB mutations in 24 patients. They suggested that there is a clinical continuum between ML III and ML II, and the classification of these diseases should be based on the age of onset, clinical symptoms, and severity. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
|
|
In affected members of a large consanguineous 6-generation Pakistani family with stuttering (STUT2; 609261) showing linkage to chromosome 12q, Kang et al. (2010) identified a glu1200-to-lys (E1200K) variant in the GNPTAB gene. Thirteen affected individuals were heterozygous, and 12 were homozygous. However, the variant did not completely segregate with the disorder: 3 noncarriers were affected, and 2 homozygous E1200K carriers and 9 heterozygous E1200K carriers were unaffected. Kang et al. (2010) suggested nonpenetrance in these individuals. The authors identified 3 additional variants in the GNPTAB gene in 4 additional unrelated individuals with stuttering. None of the individuals had features of mucolipidosis. Study of additional families and individuals identified the E1200K variant in 3 other Pakistani families with stuttering, in 1 North American patient of Asian Indian ancestry, and in 1 Pakistani control. The E1200K variant was not found in 192 chromosomes from unaffected Pakistani controls or in 552 chromosomes from North American controls. By studying other genes in the lysosomal enzyme-targeting pathway, Kang et al. (2010) identified 3 variants each in the GNPTG (607838) and NAGPA (607985) genes that were found in 11 of 270 North American/British patients with stuttering but not in 276 controls. Kang et al. (2010) concluded that variations in genes governing lysosomal metabolism may be susceptibility factors for nonsyndromic persistent stuttering. </p><p>By haplotype analysis of 8 unrelated individuals who were heterozygous or homozygous for the G1200K variant, Fedyna et al. (2011) determined that it arose as a founder allele 572 generations, or 14,300 years ago. Haplotype analysis identified a common 6.67-kb haplotype containing the variant. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Genotype/Phenotype Correlations</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Otomo et al. (2009) identified 18 GNPTAB mutations, including 14 novel mutations, among 25 unrelated Japanese patients with ML II and 15 Japanese patients with ML III. The most common mutations were R1189X (607840.0004), which was found in 41% of alleles, and F374L (607840.0015), which was found in 10% of alleles. Homozygotes or compound heterozygotes of nonsense and frameshift mutations contributed to the more severe phenotype. In all, 73 GNPTAB mutations were detected in the 80 alleles. In a review of the reported clinical features, most ML II patients had impairment in standing alone, walking without support, and speaking single words compared to those with ML III. The frequencies of heart murmur, inguinal hernia, and hepatomegaly and/or splenomegaly did not differ between ML II and III patients. </p><p>Encarnacao et al. (2009) identified GNPTAB mutations in 9 mostly Portuguese patients with ML II. Eight of 9 patients had a nonsense or frameshift mutation, the most common being a 2-bp deletion (607840.0011) that was found in 45% of the mutant alleles; one patient with ML II was homozygous for a missense mutation. Three additional patients with a less severe phenotype consistent with ML III had missense mutations. Encarnacao et al. (2009) concluded that patients with ML II alpha/beta are almost all associated with the presence of nonsense or frameshift mutations in homozygosity, whereas the presence of at least 1 mild mutation in the GNPTAB gene is associated with ML III alpha/beta. </p><p>Cathey et al. (2010) identified 51 pathogenic changes in the GNPTAB gene, including 42 novel mutations, among 61 probands mostly from the U.S. with ML II or ML III. Thirty-four probands, including 13 with ML II, 14 with ML III, and 7 with an intermediate phenotype, were studied in detail. Those with ML II had a more severe phenotype, with evidence of craniofacial and orthopedic problems at birth, severe psychomotor retardation, and enzyme activity of less than 1% of control values. Growth, speech, ambulation, and cognitive function were impaired. Those with ML III had enzyme activity of 1 to 10% of control values, minimal delays in milestones, and later onset of skeletal problems. ML II was associated with frameshift or truncating mutations, whereas ML III was associated with hypomorphic mutations. The most common mutation was 3503delTC (607840.0011), found in 18 ML II and 4 ML III patients. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In an N-ethyl-N-nitrosourea mutagenesis screen, Paton et al. (2014) identified a line of mice with a novel mutation, termed Nymphe (nym), that caused growth retardation and ataxic gate. They identified the nym mutation as a c.2601T-A transversion in exon 13 of the Gnptab gene, resulting in a tyr867-to-ter (Y867X) substitution in the Gnptab preprotein prior to the cleavage signal between the alpha and beta subunits. The mutation resulted in a truncated alpha subunit, complete lack of the beta subunit, and retention of the alpha subunit in the endoplasmic reticulum. Whereas nym/+ mice appeared normal, nym/nym mutants had facial and skeletal abnormalities from birth, reduced fertility, progressive ataxia and motor incoordination, and elevated mortality. Nym/nym serum had abnormally high activity of lysosomal hydrolases, and tissues showed inclusion bodies indicative of lysosomal storage. Nym/nym brain showed atrophy, with progressive loss of cerebellar Purkinje cells. Paton et al. (2014) concluded that the nym mutation produces a mouse model that recapitulates the human pathology of mucolipidosis II. </p><p>Barnes et al. (2016) engineered mice to carry a homozygous glu1179-to-lys mutation in the Gnptab gene, which is homologous to the glu1200-to-lys mutation in human GNPTAB. Compared with wildtype pups, pups with the mutation emitted fewer vocalizations per unit time when separated from their dam. They also showed longer pauses between vocalizations and were more stereotyped in their vocalizations than wildtype littermates. Gnptab missense pups were similar to wildtype on an extensive battery of nonvocal behaviors. Speech from people who stutter showed similar abnormalities when compared with control speech. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>15 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 MUCOLIPIDOSIS III ALPHA/BETA, ATYPICAL</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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GNPTAB, G-A, EX7
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<br />
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SNP: rs281865025,
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ClinVar: RCV000002888, RCV000031990, RCV001377361, RCV001731275, RCV001831508
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In a 47-year-old female who presented with dilated cardiomyopathy and mild neuropathy and was found to have mucolipidosis III (252600), Steet et al. (2005) identified a homozygous G-A transition in the last nucleotide of exon 7 of the GNPTAB gene, resulting in skipping of exon 7 and the production of a minimal amount of functional enzyme. The patient exhibited none of the connective tissue anomalies characteristic of mucolipidosis III, and the authors stated that this was the first example of the disease presenting in an adult patient. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0002 MUCOLIPIDOSIS III ALPHA/BETA</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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GNPTAB, ASP407GLY
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<br />
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SNP: rs137852895,
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ClinVar: RCV000002889
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a 14-year-old boy with a mild clinical phenotype of mucolipidosis III (252600), Tiede et al. (2005) identified homozygosity for a 1220A-C transversion in exon 10 of the GNPTAB gene, resulting in an asp407-to-ala (D407A) substitution. Both parents were heterozygous for the mutation, which was not found in 200 normal alleles. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 MUCOLIPIDOSIS II ALPHA/BETA</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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GNPTAB, GLN104TER
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<br />
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|
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SNP: rs137852896,
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|
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ClinVar: RCV000002890, RCV001380992
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</span>
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|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 1-year-old Korean girl with mucolipidosis II (252500), Paik et al. (2005) identified compound heterozygosity for a 310C-T transition in exon 3 and a 3565C-T transition in exon 19 of the GNPTAB gene, resulting in a gln104-to-ter (Q104X) and an arg1189-to-ter (R1189X; 607840.0004) substitution, respectively. The patient had growth retardation, developmental delay, hypotonia, severe skeletal deformity with hip subluxation, gum hypertrophy, and severe mitral and aortic valve prolapse with regurgitation. </p>
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|
</span>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 MUCOLIPIDOSIS II ALPHA/BETA</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
MUCOLIPIDOSIS III ALPHA/BETA, INCLUDED
|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
GNPTAB, ARG1189TER
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|
|
<br />
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|
|
SNP: rs137852897,
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|
|
gnomAD: rs137852897,
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|
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ClinVar: RCV000002891, RCV000002892, RCV000664622, RCV000723447, RCV001193438, RCV003398424
|
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|
|
</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg1189-to-ter (R1189X) mutation in the GNPTAB gene that was found in compound heterozygous state in a patient with mucolipidosis II (252500) by Paik et al. (2005), see 607840.0003. </p><p>Otomo et al. (2009) identified a 3565C-T transition in the GNPTAB gene, resulting in an arg1189-to-ter (R1189X) substitution in 33 (41%) of 80 mutant GNPTAB alleles from 40 unrelated Japanese patients with mucolipidosis II or mucolipidosis III (252600). Patients with the more severe mucolipidosis II tended to have the R1189X mutation in homozygosity or in compound heterozygosity with a truncating mutation. None of the patients with the less severe mucolipidosis III carried R1189X in homozygosity; most were compound heterozygous for R1189X and F374L (607840.0015). </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
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|
</div>
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</div>
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|
<div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 MUCOLIPIDOSIS II ALPHA/BETA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
GNPTAB, SER1058TER
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|
|
|
<br />
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|
|
|
SNP: rs137852898,
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|
|
|
gnomAD: rs137852898,
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|
|
|
|
|
ClinVar: RCV000002893
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|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 2-year-old Korean girl with mucolipidosis II (252500), Paik et al. (2005) identified compound heterozygosity for a 3173C-G transversion in exon 16 and a 2-bp deletion (3474delTA) in exon 19 of the GNPTAB gene, resulting in a ser1058-to-ter (S1058X) substitution and a frameshift leading to premature termination (607840.0006), respectively. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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|
<div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 MUCOLIPIDOSIS II ALPHA/BETA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
GNPTAB, 2-BP DEL, 3474TA
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|
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|
|
|
<br />
|
|
|
|
SNP: rs281865038,
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|
|
|
gnomAD: rs281865038,
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|
|
|
|
|
ClinVar: RCV000002894
|
|
|
|
|
|
</span>
|
|
</div>
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 2-bp deletion in the GNPTAB gene (3474delTA) that was found in compound heterozygous state in a patient with mucolipidosis II (252500) by Paik et al. (2005), see 607840.0005. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
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|
</div>
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</div>
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<div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MUCOLIPIDOSIS II ALPHA/BETA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
GNPTAB, TRP894TER
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|
|
|
<br />
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|
|
|
SNP: rs137852899,
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|
|
|
ClinVar: RCV000002895
|
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|
|
|
</span>
|
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</div>
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 1-year-old Korean girl with mucolipidosis II (252500), Paik et al. (2005) identified compound heterozygosity for a 2681G-A transition in exon 13 of the GNPTAB gene resulting in a trp894-to-ter (W894X) substitution and an R1189X mutation (607840.0004). The patient had growth retardation, developmental delay, gum hypertrophy, joint restriction, coxa valga, and coronary artery atresia requiring coronary artery bypass surgery. </p>
|
|
</span>
|
|
</div>
|
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 MUCOLIPIDOSIS III ALPHA/BETA</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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GNPTAB, IVS13, G-A, +1
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<br />
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|
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SNP: rs281865031,
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|
|
gnomAD: rs281865031,
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|
|
|
|
|
ClinVar: RCV000031976, RCV000664616, RCV001193439, RCV001274138, RCV001293695, RCV001572905, RCV004528068
|
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|
|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 Korean girls with mucolipidosis IIIA (252600), Paik et al. (2005) identified compound heterozygosity for a splice site mutation, a 2715+1G-A transition in intron 13 of the GNPTAB gene, with an R1189X mutation (607840.0004) and a 2-bp deletion (2574delGA) in exon 13 (607840.0009), respectively. The 2574delGA mutation results in premature termination. </p>
|
|
</span>
|
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</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 MUCOLIPIDOSIS III ALPHA/BETA</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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GNPTAB, 2-BP DEL, 2574GA
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<br />
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|
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SNP: rs281865029,
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gnomAD: rs281865029,
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ClinVar: RCV000031974, RCV000671157
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</span>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>For discussion of the 2-bp deletion in the GNPTAB gene (2574delGA) that was found in compound heterozygous state in patients with mucolipidosis IIIA (252600) by Paik et al. (2005), see 607840.0008. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0010 MUCOLIPIDOSIS II ALPHA/BETA</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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GNPTAB, 1-BP INS, 1625C
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<br />
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SNP: rs281865027,
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ClinVar: RCV000002898
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with mucolipidosis II (252500), Tiede et al. (2005) identified homozygosity for a 1-bp insertion in exon 13 of the GNPTAB gene, resulting in a premature termination directly after the putative second Notch repeat-like domain. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0011 MUCOLIPIDOSIS II ALPHA/BETA</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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MUCOLIPIDOSIS III ALPHA/BETA, INCLUDED
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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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GNPTAB, 2-BP DEL, 3503TC
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<br />
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SNP: rs34002892,
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gnomAD: rs34002892,
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ClinVar: RCV000002899, RCV000002900, RCV000082192, RCV000623507, RCV000678389, RCV004528069
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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 8 of 9 pedigrees with mucolipidosis II (252500) and 5 of 7 with mucolipidosis IIIA (252600), Kudo et al. (2006) identified a frameshift mutation in the GNPTAB gene consisting of deletion of 2 nucleotides (3665_3666delTC based on numbering of the first base in the initiation codon of a BAC clone) beginning at leu1168 and leading to premature termination at amino acid 1172 (Leu1168fsTer1172). This mutation was the most frequent in their study and was found in both the homozygous and compound heterozygous state, in combination with severe mutations (i.e., mutations preventing the generation of active enzyme) in ML II and with mild mutations (i.e., mutations allowing the generation of active enzyme) in ML IIIA. </p><p>In 27 parents of 16 deceased French Canadian children with mucolipidosis II alpha/beta, Plante et al. (2008) identified the 2-bp deletion (which they referred to as 3503_3504delTC based on numbering of the first nucleotide of the start codon as +1; rs34002892) in exon 19 of the GNPTAB gene, resulting in a frameshift and premature termination. All parents carried the mutation in the heterozygous state, indicating that the children were likely homozygous. Genealogic data showed 6 founders (3 couples) with a high probability of having introduced the mutation in the population; all originated from France and were married in the Quebec region in the second half of the 17th century. Plante et al. (2008) noted that the carrier rate of mucolipidosis II is estimated to be 1 in 39 in the Saguenay-Lac-Saint-Jean region. </p><p>Encarnacao et al. (2009) identified GNPTAB mutations in 9 mostly Portuguese patients with ML II. Eight of 9 patients had a nonsense or frameshift mutation, the most common being the 2-bp deletion (3503delTC) that was found in 45% of the mutant alleles. </p><p>By haplotype analysis of 44 carriers of the 3503delTC mutation from various populations, Coutinho et al. (2011) found that 59 (97%) of 61 mutant chromosomes shared a common haplotype covering 4 of the 5 polymorphic markers analyzed, indicating a strong founder effect. The 2 remaining chromosomes, both from Italian patients, differed by alleles only at 1 marker. A common haplotype encompassing the 3503delTC mutation was shared by individuals of Italian, Arab-Muslim, Turkish, Argentinian, Brazilian, Irish Traveller, Portuguese, and Canadian origin. The mutation was estimated to have occurred about 2,063 years ago, most likely in a peri-Mediterranean region. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0012 MUCOLIPIDOSIS II ALPHA/BETA</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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GNPTAB, IVS17DS, G-A, +1
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<br />
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SNP: rs34940801,
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gnomAD: rs34940801,
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ClinVar: RCV000002901, RCV001328325, RCV001381208, RCV001781170
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
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<p>In a patient with type II mucolipidosis (252500), Kudo et al. (2006) described a splice site mutation in the GNPTAB gene, IVS17+1G-A, that was predicted to cause skipping of exon 17 and a frameshift beginning at pro1084 and ending with premature termination at residue 1085 (P1084fsX1085). This mutation was found in compound heterozygosity with the FS1172 mutation (607840.0011). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 MUCOLIPIDOSIS III ALPHA/BETA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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GNPTAB, IVS17DS, T-G, +6
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<br />
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SNP: rs34788341,
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gnomAD: rs34788341,
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ClinVar: RCV000002902, RCV000031982, RCV000032336, RCV000665095, RCV001781171
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a family with 2 affected sibs and in 2 patients with mucolipidosis IIIA (252900), Kudo et al. (2006) described a donor splice site mutation in intron 17 of the GNPTAB gene, IVS17+6T-G, that results in skipping of exon 17 and a frameshift with a premature termination at residue 1085 (Pro1084fsTer1172). This same result was observed in another intron 17 splice site mutation in a patient with ML II (607840.0012). The former intron 17 splice site mutation was designated type I and the latter type II. Although the mRNA sequences derived from these 2 mutations are the same, the GlcNAc-phosphotransferase activities and clinical outcomes are different; fibroblasts with the type I mutation exhibited less than 0.1% activity, whereas those carrying the type II mutation exhibited 1 to 3% GlcNAc-phosphotransferase activity. That the type II mutation was located outside the invariant splice site was suggested as a possible cause of the greater activity. </p>
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</span>
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</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 MUCOLIPIDOSIS III ALPHA/BETA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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|
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GNPTAB, LYS4GLN
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<br />
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SNP: rs34159654,
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gnomAD: rs34159654,
|
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|
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ClinVar: RCV000002903, RCV000031965, RCV000669013
|
|
|
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|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family and a unrelated single patient with mucolipidosis IIIA (252900), Kudo et al. (2006) identified an A-to-C transversion in exon 1 of the GNPTAB gene, resulting in a lys4-to-gln (K4Q) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
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|
|
</div>
|
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 MUCOLIPIDOSIS III ALPHA/BETA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
MUCOLIPIDOSIS II ALPHA/BETA, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GNPTAB, PHE374LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852900,
|
|
|
|
|
|
|
|
ClinVar: RCV000002904, RCV000002905
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Otomo et al. (2009) identified a 1120T-C transition in exon 10 of the GNPTAB gene, resulting in a phe374-to-leu (F374L) substitution in 7 of 15 unrelated Japanese patients with mucolipidosis III (252600). Most were in compound heterozygosity with R1189X (607840.0004). Only 1 of 25 patients with a diagnosis of the more severe mucolipidosis II (252500) carried the F374L mutation; the second mutant allele in this patient was not identified. However, Otomo et al. (2009) stated that this patient had a relatively attenuated course, suggesting that F374L is associated with milder clinical manifestations. The F374L mutation occurred in 8 (10%) of 80 mutant alleles. Analysis of surrounding polymorphisms suggested a founder effect. </p>
|
|
</span>
|
|
</div>
|
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|
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<div>
|
|
<br />
|
|
</div>
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|
</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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|
|
|
<div>
|
|
<ol>
|
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<li>
|
|
<p class="mim-text-font">
|
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Bao, M., Booth, J. L., Elmendorf, B. J., Canfield, W. M.
|
|
<strong>Bovine UDP-N-acetylglucosamine:lysosomal-enzyme N-acetylglucosamine-1-phosphotransferase: I. Purification and subunit structure.</strong>
|
|
J. Biol. Chem. 271: 31437-31445, 1996.
|
|
|
|
|
|
[PubMed: 8940155]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.271.49.31437]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bao, M., Elmendorf, B. J., Booth, J. L., Drake, R. R., Canfield, W. M.
|
|
<strong>Bovine UDP-N-acetylglucosamine:lysosomal-enzyme N-acetylglucosamine-1-phosphotransferase: II. Enzymatic characterization and identification of the catalytic subunit.</strong>
|
|
J. Biol. Chem. 271: 31446-31451, 1996.
|
|
|
|
|
|
[PubMed: 8940156]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.271.49.31446]
|
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|
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|
</p>
|
|
</li>
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|
|
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<li>
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<p class="mim-text-font">
|
|
Bargal, R., Zeigler, M., Abu-Libdeh, B., Zuri, V., Mandel, H., Neriah, Z. B., Stewart, F., Elcioglu, N., Hindi, T., Le Merrer, M., Bach, G., Raas-Rothschild, A.
|
|
<strong>When mucolipidosis III meets mucolipidosis II: GNPTA gene mutations in 24 patients.</strong>
|
|
Molec. Genet. Metab. 88: 359-363, 2006. Note: Erratum: Molec. Genet. Metab. 91: 299 only, 2007.
|
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|
[PubMed: 16630736]
|
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|
|
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[Full Text: https://doi.org/10.1016/j.ymgme.2006.03.003]
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Barnes, T. D., Wozniak, D. F., Gutierrez, J., Han, T.-U., Drayna, D., Holy, T. E.
|
|
<strong>A mutation associated with stuttering alters mouse pup ultrasonic vocalizations.</strong>
|
|
Curr. Biol. 26: 1009-1018, 2016.
|
|
|
|
|
|
[PubMed: 27151663]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cub.2016.02.068]
|
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</p>
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|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Canfield, W. M., Bao, M., Pan, J., Brewer, A. D. K., Pan, H., Roe, B., Raas-Rothschild, A.
|
|
<strong>Mucolipidosis II and mucolipidosis IIIA are caused by mutations in the GlcNAc-phosphotransferase alpha/beta gene on chromosome 12p. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 63: A15 only, 1998.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cathey, S. S., Leroy, J. G., Wood, T., Eaves, K., Simensen, R. J., Kudo, M., Stevenson, R. E., Friez, M. J.
|
|
<strong>Phenotype and genotype in mucolipidoses II and III alpha/beta: a study of 61 probands.</strong>
|
|
J. Med. Genet. 47: 38-48, 2010.
|
|
|
|
|
|
[PubMed: 19617216]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2009.067736]
|
|
|
|
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</p>
|
|
</li>
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|
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<li>
|
|
<p class="mim-text-font">
|
|
Coutinho, M. F., Encarnacao, M., Gomes, R., da Silva Santos, L., Martins, S., Sirois-Gagnon, D., Bargal, R., Filocamo, M., Raas-Rothschild, A., Tappino, B., Laprise, C., Cury, G. K., Schwartz, I. V., Artigalas, O., Prata, M. J., Alves, S.
|
|
<strong>Origin and spread of a common deletion causing mucolipidosis type II: insights from patterns of haplotypic diversity.</strong>
|
|
Clin. Genet. 80: 273-280, 2011.
|
|
|
|
|
|
[PubMed: 20880125]
|
|
|
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|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2010.01539.x]
|
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Encarnacao, M., Lacerda, L., Costa, R., Prata, M. J., Coutinho, M. F., Ribeiro, H., Lopes, L., Pineda, M., Ignatius, J., Galvez, H., Mustonen, A., Vieira, P., Lima, M. R., Alves, S.
|
|
<strong>Molecular analysis of the GNPTAB and GNPTG genes in 13 patients with mucolipidosis type II or type III - identification of eight novel mutations.</strong>
|
|
Clin. Genet. 76: 76-84, 2009.
|
|
|
|
|
|
[PubMed: 19659762]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2009.01185.x]
|
|
|
|
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|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fedyna, A., Drayna, D., Kang, C.
|
|
<strong>Characterization of a mutation commonly associated with persistent stuttering: evidence for a founder mutation.</strong>
|
|
J. Hum. Genet. 56: 80-82, 2011.
|
|
|
|
|
|
[PubMed: 20944643]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/jhg.2010.125]
|
|
|
|
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|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kang, C., Riazuddin, S., Mundorff, J., Krasnewich, D., Friedman, P., Mullikin, J. C., Drayna, D.
|
|
<strong>Mutations in the lysosomal enzyme-targeting pathway and persistent stuttering.</strong>
|
|
New Eng. J. Med. 362: 677-685, 2010.
|
|
|
|
|
|
[PubMed: 20147709]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa0902630]
|
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|
|
</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Kudo, M., Bao, M., D'Souza, A., Ying, F., Pan, H., Roe, B. A., Canfield, W. M.
|
|
<strong>The alpha- and beta-subunits of the human UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase are encoded by a single cDNA.</strong>
|
|
J. Biol. Chem. 280: 36141-36149, 2005. Note: Erratum: J. Biol. Chem. 280: 42476 only, 2005.
|
|
|
|
|
|
[PubMed: 16120602]
|
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|
|
[Full Text: https://doi.org/10.1074/jbc.M509008200]
|
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</p>
|
|
</li>
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|
<li>
|
|
<p class="mim-text-font">
|
|
Kudo, M., Brem, M. S., Canfield, W. M.
|
|
<strong>Mucolipidosis II (I-cell disease) and mucolipidosis IIIA (classical pseudo-Hurler polydystrophy) are caused by mutations in the GlcNAc-phosphotransferase alpha/beta-subunits precursor gene.</strong>
|
|
Am. J. Hum. Genet. 78: 451-463, 2006.
|
|
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|
|
|
[PubMed: 16465621]
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|
|
[Full Text: https://doi.org/10.1086/500849]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Marschner, K., Kollmann, K., Schweizer, M., Braulke, T., Pohl, S.
|
|
<strong>A key enzyme in the biogenesis of lysosomes is a protease that regulates cholesterol metabolism.</strong>
|
|
Science 333: 87-90, 2011.
|
|
|
|
|
|
[PubMed: 21719679]
|
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|
|
[Full Text: https://doi.org/10.1126/science.1205677]
|
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|
</p>
|
|
</li>
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|
|
<li>
|
|
<p class="mim-text-font">
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Mueller, O. T., Wasmuth, J. J., Murray, J. C., Lozzio, C. B., Lovrien, E. W., Shows, T. B.
|
|
<strong>Chromosomal assignment of N-acetylglucosaminylphosphotransferase, the lysosomal hydrolase targeting enzyme deficient in mucolipidosis II and III. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 46: 664, 1987.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Otomo, T., Muramatsu, T., Yorifuji, T., Okuyama, T., Nakabayashi, H., Fukao, T., Ohura, T., Yoshino, M., Tanaka, A., Okamoto, N., Inui, K., Ozono, K., Sakai, N.
|
|
<strong>Mucolipidosis II and III alpha/beta: mutation analysis of 40 Japanese patients showed genotype-phenotype correlation.</strong>
|
|
J. Hum. Genet. 54: 145-151, 2009.
|
|
|
|
|
|
[PubMed: 19197337]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/jhg.2009.3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Paik, K. H., Song, S. M., Ki, C. S., Yu, H.-W., Kim, J. S., Min, K. H., Chang, S. H., Yoo, E. J., Lee, I. J., Kwan, E. K., Han, S. J., Jin, D.-K.
|
|
<strong>Identification of mutations in the GNPTA (MGC4170) gene coding for GlcNAc-phosphotransferase alpha/beta subunits in Korean patients with mucolipidosis type II or type IIIA.</strong>
|
|
Hum. Mutat. 26: 308-314, 2005.
|
|
|
|
|
|
[PubMed: 16116615]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20205]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Paton, L., Bitoun, E., Kenyon, J., Priestman, D. A., Oliver, P. L., Edwards, B., Platt, F. M., Davies, K. E.
|
|
<strong>A novel mouse model of a patient mucolipidosis II mutation recapitulates disease pathology.</strong>
|
|
J. Biol. Chem. 289: 26709-26721, 2014.
|
|
|
|
|
|
[PubMed: 25107912]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M114.586156]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
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<p class="mim-text-font">
|
|
Plante, M., Claveau, S., Lepage, P., Lavoie, E.-M., Brunet, S., Roquis, D., Morin, C., Vezina, H., Laprise, C.
|
|
<strong>Mucolipidosis II: a single causal mutation in the N-acetylglucosamine-1-phosphotransferase gene (GNPTAB) in a French Canadian founder population.</strong>
|
|
Clin. Genet. 73: 236-244, 2008.
|
|
|
|
|
|
[PubMed: 18190596]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2007.00954.x]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Steet, R. A., Hullin, R., Kudo, M., Martinelli, M., Bosshard, N. U., Schaffner, T., Kornfeld, S. Steinmann, B.
|
|
<strong>A splicing mutation in the alpha/beta GlcNAc-1-phosphotransferase gene results in an adult onset form of mucolipidosis III associated with sensory neuropathy and cardiomyopathy.</strong>
|
|
Am. J. Med. Genet. 132A: 369-375, 2005.
|
|
|
|
|
|
[PubMed: 15633164]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.30498]
|
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|
|
|
|
</p>
|
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</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Tiede, S., Muschol, N., Reutter, G., Cantz, M., Ullrich, K., Braulke, T.
|
|
<strong>Missense mutations in N-acetylglucosamine-1-phosphotransferase alpha/beta subunit gene in a patient with mucolipidosis III and a mild clinical phenotype.</strong>
|
|
Am. J. Med. Genet. 137A: 235-240, 2005.
|
|
|
|
|
|
[PubMed: 16094673]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.30868]
|
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Tiede, S., Storch, S., Lubke, T., Henrissat, B., Bargal, R., Raas-Rothschild, A., Braulke, T.
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<strong>Mucolipidosis II is caused by mutations in GNPTA encoding the alpha/beta GlcNAc-1-phosphotransferase.</strong>
|
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Nature Med. 11: 1109-1112, 2005.
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[PubMed: 16200072]
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[Full Text: https://doi.org/10.1038/nm1305]
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</p>
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Vidgoff, J., Rowe, S., Stafford, R., Buist, N. R. M., Lovrien, E. W.
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<strong>Localization of the gene for I-cell disease (mucolipidosis II). (Abstract)</strong>
|
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Am. J. Hum. Genet. 34: 64A, 1982.
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