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Entry
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- *605514 - PROTOCADHERIN 15; PCDH15
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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">*605514</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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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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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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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="#biochemicalFeatures">Biochemical Features</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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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/605514">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=ENSG00000150275;t=ENST00000644397" 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=65217" 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=605514" 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=ENSG00000150275;t=ENST00000644397" 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_001142763,NM_001142764,NM_001142765,NM_001142766,NM_001142767,NM_001142768,NM_001142769,NM_001142770,NM_001142771,NM_001142772,NM_001142773,NM_001354404,NM_001354411,NM_001354420,NM_001354429,NM_001354430,NM_001384140,NM_033056,XM_047425663,XM_047425664" 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_001384140" 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=605514" 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=05698&isoform_id=05698_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/PCDH15" 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/14581464,15072441,38679262,57997201,115387123,116242702,119574536,119574537,193785246,194591873,194591875,194591877,218505775,218505777,218505779,218505781,218505783,218505785,218505787,218505789,218505791,218505793,218505798,1229732604,1231802440,1231802442,1231802444,1237938304,1847613777,2217278412,2217278414,2462520740,2462520742" 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/Q96QU1" 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=65217" 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=ENSG00000150275;t=ENST00000644397" 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=PCDH15" 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=PCDH15" 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+65217" 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/PCDH15" 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:65217" 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/65217" 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=chr10&hgg_gene=ENST00000644397.2&hgg_start=53802771&hgg_end=55627942&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:14674" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:14674" 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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=605514[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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=605514[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/PCDH15/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/ENSG00000150275" 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=PCDH15" 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=PCDH15" 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=PCDH15" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="#mimLocusSpecificDBsFold" id="mimLocusSpecificDBsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A gene-specific database of variation."><span id="mimLocusSpecificDBsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Locus Specific DBs</div>
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<div id="mimLocusSpecificDBsFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="http://www.LOVD.nl/PCDH15" title="Retinal and hearing impairment genetic mutation database PCDH15" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Retinal and hearing impair…</a></div><div style="margin-left: 0.5em;"><a href="http://www.retina-international.org/files/sci-news/pcdhmut.htm" title="Mutations of the Protocadherin 15 Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Mutations of the Protocadh…</a></div><div style="margin-left: 0.5em;"><a href="http://www.umd.be/PCDH15/" title="The UMD PCDH15 mutations database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">The UMD PCDH15 mutations d…</a></div><div style="margin-left: 0.5em;"><a href="https://research.cchmc.org/LOVD2/home.php?select_db=PCDH15" title="CCHMC Molecular Genetics Laboratory Mutation Database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">CCHMC Molecular Genetics L…</a></div>
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</div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=PCDH15&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/PA32999" 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:14674" 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/FBgn0039709.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:1891428" 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/PCDH15#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:1891428" 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/65217/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/OMIA002548/" 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=65217" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00000397;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-030616-3" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=PCDH15&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</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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605514
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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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PROTOCADHERIN 15; PCDH15
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=PCDH15" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">PCDH15</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/10/209?start=-3&limit=10&highlight=209">10q21.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr10:53802771-55627942&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'})">10:53,802,771-55,627,942</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover 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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<span class="hidden-sm hidden-xs pull-right">
|
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<a href="/clinicalSynopsis/table?mimNumber=609533,601067,602083" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
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</a>
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</span>
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="3">
|
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<span class="mim-font">
|
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<a href="/geneMap/10/209?start=-3&limit=10&highlight=209">
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10q21.1
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</a>
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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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Deafness, autosomal recessive 23
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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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<a href="/entry/609533"> 609533 </a>
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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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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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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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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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<p>Using a mouse Pcdh15 cDNA probe to screen a human genomic P1-derived artificial chromosome (PAC) library, Alagramam et al. (<a href="#5" class="mim-tip-reference" title="Alagramam, K. N., Murcia, C. L., Kwon, H. Y., Pawlowski, K. S., Wright, C. G., Woychik, R. P. <strong>The mouse Ames waltzer hearing-loss mutant is caused by mutation of Pcdh15, a novel protocadherin gene.</strong> Nature Genet. 27: 99-102, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11138007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11138007</a>] [<a href="https://doi.org/10.1038/83837" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11138007">2001</a>, <a href="#6" class="mim-tip-reference" title="Alagramam, K. N., Yuan, H., Kuehn, M. H., Murcia, C. L., Wayne, S., Srisailpathy, C. R. S., Lowry, R. B., Knaus, R., Van Laer, L., Bernier, F. P., Schwartz, S., Lee, C., Morton, C. C., Mullins, R. F., Ramesh, A., Van Camp, G., Hageman, G. S., Woychik, R. P., Smith, R. J. H. <strong>Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F.</strong> Hum. Molec. Genet. 10: 1709-1718, 2001. Note: Erratum: Hum. Molec. Genet. 10: 2603 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11487575/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11487575</a>] [<a href="https://doi.org/10.1093/hmg/10.16.1709" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11487575">2001</a>) identified the human PCDH15 gene. The CDH15 cDNA contains an open reading frame (ORF) that encodes 1,955 amino acids (<a href="#5" class="mim-tip-reference" title="Alagramam, K. N., Murcia, C. L., Kwon, H. Y., Pawlowski, K. S., Wright, C. G., Woychik, R. P. <strong>The mouse Ames waltzer hearing-loss mutant is caused by mutation of Pcdh15, a novel protocadherin gene.</strong> Nature Genet. 27: 99-102, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11138007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11138007</a>] [<a href="https://doi.org/10.1038/83837" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11138007">Alagramam et al., 2001</a>). The predicted protein has 11 cadherin repeats, 1 transmembrane domain and a cytoplasmic domain that contains 2 proline-rich regions. By Northern blot analysis, <a href="#6" class="mim-tip-reference" title="Alagramam, K. N., Yuan, H., Kuehn, M. H., Murcia, C. L., Wayne, S., Srisailpathy, C. R. S., Lowry, R. B., Knaus, R., Van Laer, L., Bernier, F. P., Schwartz, S., Lee, C., Morton, C. C., Mullins, R. F., Ramesh, A., Van Camp, G., Hageman, G. S., Woychik, R. P., Smith, R. J. H. <strong>Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F.</strong> Hum. Molec. Genet. 10: 1709-1718, 2001. Note: Erratum: Hum. Molec. Genet. 10: 2603 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11487575/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11487575</a>] [<a href="https://doi.org/10.1093/hmg/10.16.1709" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11487575">Alagramam et al. (2001)</a> demonstrated PCDH15 expression in human adult brain, lung, and kidney. Expression in human fetal brain was assumed since the human PCDH15 cDNA was obtained by screening a fetal brain library. Additional experiments by RT-PCR and direct sequencing revealed expression in other human adult tissues and human fetal cochlea. Immunohistochemistry detected PCDH15 expression in the inner and outer synaptic layers and the nerve fiber layer in human adult and fetal retinas. Additional reactivity in the region of the outer limiting membrane/photoreceptor cell inner segments was observed in adult but not fetal retina. In human fetal cochlea, <a href="#6" class="mim-tip-reference" title="Alagramam, K. N., Yuan, H., Kuehn, M. H., Murcia, C. L., Wayne, S., Srisailpathy, C. R. S., Lowry, R. B., Knaus, R., Van Laer, L., Bernier, F. P., Schwartz, S., Lee, C., Morton, C. C., Mullins, R. F., Ramesh, A., Van Camp, G., Hageman, G. S., Woychik, R. P., Smith, R. J. H. <strong>Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F.</strong> Hum. Molec. Genet. 10: 1709-1718, 2001. Note: Erratum: Hum. Molec. Genet. 10: 2603 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11487575/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11487575</a>] [<a href="https://doi.org/10.1093/hmg/10.16.1709" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11487575">Alagramam et al. (2001)</a> detected PCDH15 expression in the supporting cells and outer sulcus cells, as well as in the spiral ganglion. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11487575+11138007" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using RT-PCR, <a href="#4" class="mim-tip-reference" title="Alagramam, K. N., Miller, N. D., Adappa, N. D., Pitts, D. R., Heaphy, J. C., Yuan, H., Smith, R. J. <strong>Promoter, alternative splice forms, and genomic structure of protocadherin 15.</strong> Genomics 90: 482-492, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17706913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17706913</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17706913[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ygeno.2007.06.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17706913">Alagramam et al. (2007)</a> identified 2 minor splice variants of mouse Pcdh15, one that skipped exon 2 and another that skipped exons 2 and 4. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17706913" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The PCSH15 gene encodes encodes a variety of isoforms with 3 to 11 ectodomains, a transmembrane domain, and a C-terminal cytoplasmic domain (CD). <a href="#2" class="mim-tip-reference" title="Ahmed, Z. M., Riazuddin, S., Aye, S., Ali, R. A., Venselaar, H., Anwar, S., Belyantseva, P. P., Qasim, M., Riazuddin, S., Friedman, T. B. <strong>Gene structure and mutant alleles of PCDH15: nonsyndromic deafness DFNB23 and type 1 Usher syndrome.</strong> Hum. Genet. 124: 215-223, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18719945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18719945</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18719945[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/10.1007/s00439-008-0543-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18719945">Ahmed et al. (2008)</a> identified 4 additional exons in the PCDH15 gene, which encode 2 novel conserved cytoplasmic domains CD2 and CD3. The amino acid sequences of CD1, CD2, and CD3 are entirely different. PCDH15-CD1 showed a limited pattern of expression and was detected in human testis, retina, and cochlea. PCDH15-CD2 expression was present in the human heart, kidney, thymus, spleen, testis, retina and cochlea. PCDH15-CD3 was widely transcribed and detected in almost all of 18 tissues tested. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18719945" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>The human PCDH15 gene contains 33 exons and spans approximately 1.6 Mb of genomic DNA (<a href="#3" class="mim-tip-reference" title="Ahmed, Z. M., Riazuddin, S., Bernstein, S. L., Ahmed, Z., Khan, S., Griffith, A. J., Morell, R. J., Friedman, T. B., Riazuddin, S., Wilcox, E. R. <strong>Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F.</strong> Am. J. Hum. Genet. 69: 25-34, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11398101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11398101</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11398101[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/10.1086/321277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11398101">Ahmed et al., 2001</a>). Only the first 2 exons are situated in the Usher syndrome type IF (USH1F; <a href="/entry/602083">602083</a>) critical region defined by one of the Pakistani families studied. The start codon is at 396 bp in exon 2 and the stop codon is at 6,263 bp in exon 33. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11398101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Ahmed, Z. M., Riazuddin, S., Bernstein, S. L., Ahmed, Z., Khan, S., Griffith, A. J., Morell, R. J., Friedman, T. B., Riazuddin, S., Wilcox, E. R. <strong>Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F.</strong> Am. J. Hum. Genet. 69: 25-34, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11398101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11398101</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11398101[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/10.1086/321277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11398101">Ahmed et al. (2001)</a> stated that 3 genes are nested in the introns of PCDH15: calcium/calmodulin-dependent protein kinase type II, presumably CAMKG (<a href="/entry/602123">602123</a>), known to map to 10q22; N-deacetylase/N-sulfotransferase 2 (NDST2; <a href="/entry/603268">603268</a>), which maps to 10q22; and plasminogen-activator, urokinase (PLAU; <a href="/entry/191840">191840</a>), previously thought to reside in 10q24. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11398101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Alagramam, K. N., Miller, N. D., Adappa, N. D., Pitts, D. R., Heaphy, J. C., Yuan, H., Smith, R. J. <strong>Promoter, alternative splice forms, and genomic structure of protocadherin 15.</strong> Genomics 90: 482-492, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17706913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17706913</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17706913[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ygeno.2007.06.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17706913">Alagramam et al. (2007)</a> determined that the promoter region of the PCDH15 gene contains a CpG island, but no TATAA or CAAT sequences. They identified suppressor and enhancer elements within the PCDH15 promoter. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17706913" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Ahmed, Z. M., Riazuddin, S., Aye, S., Ali, R. A., Venselaar, H., Anwar, S., Belyantseva, P. P., Qasim, M., Riazuddin, S., Friedman, T. B. <strong>Gene structure and mutant alleles of PCDH15: nonsyndromic deafness DFNB23 and type 1 Usher syndrome.</strong> Hum. Genet. 124: 215-223, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18719945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18719945</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18719945[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/10.1007/s00439-008-0543-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18719945">Ahmed et al. (2008)</a> identified 4 additional exons in the PCDH15 gene, for a total of 39 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18719945" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Alagramam, K. N., Murcia, C. L., Kwon, H. Y., Pawlowski, K. S., Wright, C. G., Woychik, R. P. <strong>The mouse Ames waltzer hearing-loss mutant is caused by mutation of Pcdh15, a novel protocadherin gene.</strong> Nature Genet. 27: 99-102, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11138007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11138007</a>] [<a href="https://doi.org/10.1038/83837" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11138007">Alagramam et al. (2001)</a> mapped the PCDH15 gene to chromosome 10q21-q22. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11138007" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#6" class="mim-tip-reference" title="Alagramam, K. N., Yuan, H., Kuehn, M. H., Murcia, C. L., Wayne, S., Srisailpathy, C. R. S., Lowry, R. B., Knaus, R., Van Laer, L., Bernier, F. P., Schwartz, S., Lee, C., Morton, C. C., Mullins, R. F., Ramesh, A., Van Camp, G., Hageman, G. S., Woychik, R. P., Smith, R. J. H. <strong>Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F.</strong> Hum. Molec. Genet. 10: 1709-1718, 2001. Note: Erratum: Hum. Molec. Genet. 10: 2603 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11487575/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11487575</a>] [<a href="https://doi.org/10.1093/hmg/10.16.1709" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11487575">Alagramam et al. (2001)</a> demonstrated PCDH15 expression in both retina and cochlea by RT-PCR and immunohistochemistry. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11487575" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Ahmed, Z. M., Riazuddin, S., Ahmad, J., Bernstein, S. L., Guo, Y., Sabar, M. F., Sieving, P., Riazuddin, S., Griffith, A. J., Friedman, T. B., Belyantseva, I. A., Wilcox, E. R. <strong>PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23.</strong> Hum. Molec. Genet. 12: 3215-3223, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14570705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14570705</a>] [<a href="https://doi.org/10.1093/hmg/ddg358" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14570705">Ahmed et al. (2003)</a> localized protocadherin-15 to inner ear hair cell stereocilia and to retinal photoreceptors by immunocytochemistry. The results further strengthened the importance of protocadherin-15 in the morphogenesis and cohesion of stereocilia bundles and retinal photoreceptor cell maintenance or function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14570705" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#10" class="mim-tip-reference" title="Kazmierczak, P., Sakaguchi, H., Tokita, J., Wilson-Kubalek, E. M., Milligan, R. A., Muller, U., Kachar, B. <strong>Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells.</strong> Nature 449: 87-91, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17805295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17805295</a>] [<a href="https://doi.org/10.1038/nature06091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17805295">Kazmierczak et al. (2007)</a> demonstrated that CDH23 (<a href="/entry/605516">605516</a>) and PCDH15, 2 cadherins linked to inherited forms of deafness in humans, interact to form tip links, extracellular filaments that connect the stereocilia and are thought to gate the mechanoelectrical transduction channel. Immunohistochemical studies using rodent hair cells showed that CDH23 and PCDH15 localized to the upper and lower part of tip links, respectively. The amino termini of the 2 cadherins colocalized on tip link filaments. Biochemical experiments showed that CDH23 homodimers interact in trans with PCDH15 homodimers to form a filament with structural similarity to tip links. Ions that affected tip link integrity and a mutation in PCDH15 that causes a recessive form of deafness (see DFNB23, <a href="/entry/609533">609533</a>) disrupted interactions between CDH23 and PCDH15. <a href="#10" class="mim-tip-reference" title="Kazmierczak, P., Sakaguchi, H., Tokita, J., Wilson-Kubalek, E. M., Milligan, R. A., Muller, U., Kachar, B. <strong>Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells.</strong> Nature 449: 87-91, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17805295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17805295</a>] [<a href="https://doi.org/10.1038/nature06091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17805295">Kazmierczak et al. (2007)</a> concluded that their studies defined the molecular composition of tip links and provided a conceptual base for exploring the mechanisms of sensory impairment associated with mutations in CDH23 and PCDH15. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17805295" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#13" class="mim-tip-reference" title="Sotomayor, M., Weihofen, W. A., Gaudet, R., Corey, D. P. <strong>Structure of a force-conveying cadherin bond essential for inner-ear mechanotransduction.</strong> Nature 492: 128-132, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23135401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23135401</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23135401[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/nature11590" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23135401">Sotomayor et al. (2012)</a> combined crystallography, molecular dynamics simulations, and binding experiments to characterize the protocadherin-15-cadherin-23 (<a href="/entry/605516">605516</a>) bond. They found a unique cadherin interaction mechanism in which the 2 most N-terminal cadherin repeats (extracellular cadherin repeats 1 and 2) of each protein interact to form an overlapped, antiparallel heterodimer. Simulations predicted that this tip-link bond is mechanically strong enough to resist forces in hair cells. In addition, the complex was shown to become unstable in response to calcium removal owing to increased flexure of calcium-free cadherin repeats. Finally, <a href="#13" class="mim-tip-reference" title="Sotomayor, M., Weihofen, W. A., Gaudet, R., Corey, D. P. <strong>Structure of a force-conveying cadherin bond essential for inner-ear mechanotransduction.</strong> Nature 492: 128-132, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23135401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23135401</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23135401[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/nature11590" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23135401">Sotomayor et al. (2012)</a> used structures and biochemical measurements to study the molecular mechanisms by which deafness mutations disrupt tip-link function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23135401" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#3" class="mim-tip-reference" title="Ahmed, Z. M., Riazuddin, S., Bernstein, S. L., Ahmed, Z., Khan, S., Griffith, A. J., Morell, R. J., Friedman, T. B., Riazuddin, S., Wilcox, E. R. <strong>Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F.</strong> Am. J. Hum. Genet. 69: 25-34, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11398101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11398101</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11398101[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/10.1086/321277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11398101">Ahmed et al. (2001)</a> identified truncating mutations in the PCDH15 gene (<a href="#0001">605514.0001</a>-<a href="#0002">605514.0002</a>) in affected members of 2 families segregating Usher syndrome type IF (USH1F; <a href="/entry/602083">602083</a>). Northern blot analysis showed expression in the retina, consistent with the pathogenetic role of the PCDH15 gene in retinitis pigmentosa associated with USH1F. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11398101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 cell culture studies, <a href="#12" class="mim-tip-reference" title="Rebibo-Sabbah, A., Nudelman, I., Ahmed, Z. M., Baasov, T., Ben-Yosef, T. <strong>In vitro and ex vivo suppression by aminoglycosides of PCDH15 nonsense mutations underlying type 1 Usher syndrome.</strong> Hum. Genet. 122: 373-381, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17653769/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17653769</a>] [<a href="https://doi.org/10.1007/s00439-007-0410-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17653769">Rebibo-Sabbah et al. (2007)</a> demonstrated that aminoglycosides suppressed translation of several PCDH15 nonsense mutations identified in patients with Usher syndrome type 1F. The aminoglycosides resulted in variable full-length protein levels resulting from partial read-through of the nonsense mutations. <a href="#12" class="mim-tip-reference" title="Rebibo-Sabbah, A., Nudelman, I., Ahmed, Z. M., Baasov, T., Ben-Yosef, T. <strong>In vitro and ex vivo suppression by aminoglycosides of PCDH15 nonsense mutations underlying type 1 Usher syndrome.</strong> Hum. Genet. 122: 373-381, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17653769/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17653769</a>] [<a href="https://doi.org/10.1007/s00439-007-0410-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17653769">Rebibo-Sabbah et al. (2007)</a> postulated that such treatment could potentially delay the progression of retinitis pigmentosa in patients with the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17653769" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Ahmed, Z. M., Riazuddin, S., Aye, S., Ali, R. A., Venselaar, H., Anwar, S., Belyantseva, P. P., Qasim, M., Riazuddin, S., Friedman, T. B. <strong>Gene structure and mutant alleles of PCDH15: nonsyndromic deafness DFNB23 and type 1 Usher syndrome.</strong> Hum. Genet. 124: 215-223, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18719945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18719945</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18719945[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/10.1007/s00439-008-0543-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18719945">Ahmed et al. (2008)</a> identified mutations in the PCDH15 gene in 7 of 12 consanguineous Pakistani families with USH1. Six mutations were novel (see, e.g., <a href="#0009">605514.0009</a>). The remaining 5 families showed linkage to chromosome 10q21, but no pathogenic mutations in the PCDH15 gene were identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18719945" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Autosomal Recessive Deafness 23</em></strong></p><p>
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<a href="#1" class="mim-tip-reference" title="Ahmed, Z. M., Riazuddin, S., Ahmad, J., Bernstein, S. L., Guo, Y., Sabar, M. F., Sieving, P., Riazuddin, S., Griffith, A. J., Friedman, T. B., Belyantseva, I. A., Wilcox, E. R. <strong>PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23.</strong> Hum. Molec. Genet. 12: 3215-3223, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14570705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14570705</a>] [<a href="https://doi.org/10.1093/hmg/ddg358" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14570705">Ahmed et al. (2003)</a> demonstrated that nonsyndromic autosomal recessive deanfess-23 (DFNB23; <a href="/entry/609533">609533</a>) is caused by biallelic mutation in the PCDH15 gene (see <a href="#0006">605514.0006</a>-<a href="#0007">605514.0007</a>). They suggested a genotype-phenotype correlation in which hypomorphic alleles of the PCDH15 gene cause nonsyndromic hearing loss, whereas more severe mutations in this gene result in USH1F. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14570705" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Usher Syndrome Type ID/F</em></strong></p><p>
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<a href="#14" class="mim-tip-reference" title="Zheng, Q. Y., Yan, D., Ouyang, X. M., Du, L. L., Yu, H., Chang, B., Johnson, K. R., Liu, X. Z. <strong>Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans.</strong> Hum. Molec. Genet. 14: 103-111, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15537665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15537665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15537665[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddi010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15537665">Zheng et al. (2005)</a> reported 3 families with Usher syndrome type I (see <a href="/entry/601067">601067</a>) in which affected members carried mutations in both CDH23 (<a href="/entry/605516">605516</a>) and PCDH15, thus supporting a digenic model for some individuals with this phenotype. Based on an animal model, the authors concluded that CDH23 and PCDH15 play an essential long-term role in maintaining the normal organization of the stereocilia bundle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15537665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>The neuroepithelia of the inner ear contain hair cells that function as mechanoreceptors to transduce sound and motion signals. Mutations affecting these neuroepithelia cause deafness and vestibular dysfunction in humans. Ames waltzer (av) is a recessive mutation in mice that causes deafness and a balance disorder associated with degeneration of inner ear neuroepithelia. <a href="#5" class="mim-tip-reference" title="Alagramam, K. N., Murcia, C. L., Kwon, H. Y., Pawlowski, K. S., Wright, C. G., Woychik, R. P. <strong>The mouse Ames waltzer hearing-loss mutant is caused by mutation of Pcdh15, a novel protocadherin gene.</strong> Nature Genet. 27: 99-102, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11138007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11138007</a>] [<a href="https://doi.org/10.1038/83837" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11138007">Alagramam et al. (2001)</a> identified Pcdh15 as the gene that harbors the av mutation in mice. Cochlear hair cells in the av mutants showed abnormal stereocilia by 10 days after birth. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11138007" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Zheng, Q. Y., Yan, D., Ouyang, X. M., Du, L. L., Yu, H., Chang, B., Johnson, K. R., Liu, X. Z. <strong>Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans.</strong> Hum. Molec. Genet. 14: 103-111, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15537665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15537665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15537665[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddi010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15537665">Zheng et al. (2005)</a> generated mice that were heterozygous for both Cdh23(v-2J) (<a href="/entry/605516">605516</a>) and Pcdh15(av-3J) mutations on a uniform C57BL/6J background. Significant levels of hearing loss were detected in these mice when compared to age-matched single heterozygous animals or normal controls, which supported a digenic model of hearing loss. Cytoarchitectural defects in the cochlea of digenic heterozygotes, including degeneration of the stereocilia and a base-apex loss of hair cells and spiral ganglion cells, were consistent with the observed age-related hearing loss of these mice beginning with the high frequencies. The authors noted that while hearing loss was progressive in these animals, humans with heterozygosity for both CDH23 and PCDH15 mutations are congenitally deaf. <a href="#14" class="mim-tip-reference" title="Zheng, Q. Y., Yan, D., Ouyang, X. M., Du, L. L., Yu, H., Chang, B., Johnson, K. R., Liu, X. Z. <strong>Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans.</strong> Hum. Molec. Genet. 14: 103-111, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15537665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15537665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15537665[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddi010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15537665">Zheng et al. (2005)</a> concluded that CDH23 and PCDH15 play an essential long-term role in maintaining the normal organization of the stereocilia bundle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15537665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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> rs1307471318 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1307471318;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/rs1307471318?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=rs1307471318" 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=rs1307471318" 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 consanguineous Pakistani family segregating Usher syndrome type IF (USH1F; <a href="/entry/602083">602083</a>), <a href="#3" class="mim-tip-reference" title="Ahmed, Z. M., Riazuddin, S., Bernstein, S. L., Ahmed, Z., Khan, S., Griffith, A. J., Morell, R. J., Friedman, T. B., Riazuddin, S., Wilcox, E. R. <strong>Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F.</strong> Am. J. Hum. Genet. 69: 25-34, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11398101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11398101</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11398101[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/10.1086/321277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11398101">Ahmed et al. (2001)</a> found a homozygous IVS27-2A-G splice site mutation in the PCDH15 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11398101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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> rs137853001 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853001;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/rs137853001?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=rs137853001" 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=rs137853001" 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 consanguineous Pakistani family, <a href="#3" class="mim-tip-reference" title="Ahmed, Z. M., Riazuddin, S., Bernstein, S. L., Ahmed, Z., Khan, S., Griffith, A. J., Morell, R. J., Friedman, T. B., Riazuddin, S., Wilcox, E. R. <strong>Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F.</strong> Am. J. Hum. Genet. 69: 25-34, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11398101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11398101</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11398101[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/10.1086/321277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11398101">Ahmed et al. (2001)</a> identified a homozygous arg3-to-ter (R3X) missense mutation in the PCDH15 gene as the cause of Usher syndrome type IF (USH1F; <a href="/entry/602083">602083</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11398101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 Hutterite family from Alberta segregating Usher syndrome type IF (USH1F; <a href="/entry/602083">602083</a>), <a href="#6" class="mim-tip-reference" title="Alagramam, K. N., Yuan, H., Kuehn, M. H., Murcia, C. L., Wayne, S., Srisailpathy, C. R. S., Lowry, R. B., Knaus, R., Van Laer, L., Bernier, F. P., Schwartz, S., Lee, C., Morton, C. C., Mullins, R. F., Ramesh, A., Van Camp, G., Hageman, G. S., Woychik, R. P., Smith, R. J. H. <strong>Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F.</strong> Hum. Molec. Genet. 10: 1709-1718, 2001. Note: Erratum: Hum. Molec. Genet. 10: 2603 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11487575/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11487575</a>] [<a href="https://doi.org/10.1093/hmg/10.16.1709" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11487575">Alagramam et al. (2001)</a> identified a homozygous 1-bp deletion of T at nucleotide 1471 in exon 10 of the PCDH15 gene, creating a frameshift and premature stop codon after amino acid 419 in exon 11. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11487575" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Among 1,524 Schmiedeleut (S-leut) Hutterites from the United States, <a href="#8" class="mim-tip-reference" title="Chong, J. X., Ouwenga, R., Anderson, R. L., Waggoner, D. J., Ober, C. <strong>A population-based study of autosomal-recessive disease-causing mutations in a founder population.</strong> Am. J. Hum. Genet. 91: 608-620, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22981120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22981120</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22981120[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.08.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22981120">Chong et al. (2012)</a> found 38 heterozygotes and no homozygotes for the 1471delT mutation in the PCDH15 gene, for a frequency of 0.025, or 1 in 40. This is a private mutation in the Hutterite population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22981120" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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> rs111033260 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033260;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/rs111033260?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=rs111033260" 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=rs111033260" 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=RCV000005218 OR RCV000055970 OR RCV000218809 OR RCV000269122 OR RCV000477806 OR RCV000824735 OR RCV001004803 OR RCV001030749 OR RCV004734497" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005218, RCV000055970, RCV000218809, RCV000269122, RCV000477806, RCV000824735, RCV001004803, RCV001030749, RCV004734497" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005218...</a>
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<p><a href="#7" class="mim-tip-reference" title="Ben-Yosef, T., Ness, S. L., Madeo, A. C., Bar-Lev, A., Wolfman, J. H., Ahmed, Z. M., Desnick, R. J., Willner, J. P., Avraham, K. B., Ostrer, H., Oddoux, C., Griffith, A. J., Friedman, T. B. <strong>A mutation of PCDH15 among Ashkenazi Jews with the type 1 Usher syndrome.</strong> New Eng. J. Med. 348: 1664-1670, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12711741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12711741</a>] [<a href="https://doi.org/10.1056/NEJMoa021502" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12711741">Ben-Yosef et al. (2003)</a> identified a homozygous arg245-to-ter (R245X) mutation in the PCDH15 gene in cases of Usher syndrome type I (USH1F; <a href="/entry/602083">602083</a>) in Ashkenazi Jews. The R245X carrier frequencies (0.79 to 2.48%) were similar to the carrier frequencies of other genetic disorders for which routine screening is performed in this population, such as Tay-Sachs disease (3-4%), Gaucher disease (4-6%), and Canavan disease (1-2%). No R245X carriers were detected among other Jewish or non-Jewish population controls, indicating that this mutation may be unique to Ashkenazi Jews. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12711741" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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> rs113363047 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs113363047;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/rs113363047?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=rs113363047" 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=rs113363047" 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=RCV000039764 OR RCV000215699 OR RCV000514811 OR RCV001272395 OR RCV002277128 OR RCV002490550" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000039764, RCV000215699, RCV000514811, RCV001272395, RCV002277128, RCV002490550" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000039764...</a>
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<p>In a patient from the U.S. with Usher syndrome type IF (USH1F; <a href="/entry/602083">602083</a>), <a href="#11" class="mim-tip-reference" title="Ouyang, X. M., Yan, D., Du, L. L., Hejtmancik, J. F., Jacobson, S. G., Nance, W. E., Li, A. R., Angeli, S., Kaiser, M., Newton, V., Brown, S. D. M., Balkany, T., Liu, X. Z. <strong>Characterization of Usher syndrome type I gene mutations in an Usher syndrome patient population.</strong> Hum. Genet. 116: 292-299, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15660226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15660226</a>] [<a href="https://doi.org/10.1007/s00439-004-1227-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15660226">Ouyang et al. (2005)</a> identified heterozygosity for a 3-bp deletion (5601-5603delAAC) in exon 33 of the PCDH15 gene, resulting in deletion of threonine-1867. The 3-bp deletion was identified in compound heterozygosity with a PCDH15 missense mutation in another patient with USH1F. The mutation accounted for 2 (33%) of 6 mutant alleles identified by <a href="#11" class="mim-tip-reference" title="Ouyang, X. M., Yan, D., Du, L. L., Hejtmancik, J. F., Jacobson, S. G., Nance, W. E., Li, A. R., Angeli, S., Kaiser, M., Newton, V., Brown, S. D. M., Balkany, T., Liu, X. Z. <strong>Characterization of Usher syndrome type I gene mutations in an Usher syndrome patient population.</strong> Hum. Genet. 116: 292-299, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15660226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15660226</a>] [<a href="https://doi.org/10.1007/s00439-004-1227-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15660226">Ouyang et al. (2005)</a> at the PCDH15 locus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15660226" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Zheng, Q. Y., Yan, D., Ouyang, X. M., Du, L. L., Yu, H., Chang, B., Johnson, K. R., Liu, X. Z. <strong>Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans.</strong> Hum. Molec. Genet. 14: 103-111, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15537665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15537665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15537665[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddi010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15537665">Zheng et al. (2005)</a> identified 2 patients with a diagnosis of Usher syndrome type I (see <a href="/entry/601067">601067</a>) who carried this deletion in heterozygosity, in combination with an additional mutation in the CDH23 gene: a single-basepair deletion (193delC; <a href="/entry/605516#0011">605516.0011</a>) and a missense mutation (T1209A; <a href="/entry/605516#0013">605516.0013</a>), respectively. The T1209A mutation in the CDH23 gene was later reclassified as a variant of unknown function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15537665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 DEAFNESS, AUTOSOMAL RECESSIVE 23</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">rs137853002 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853002;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=rs137853002" 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=rs137853002" 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=RCV000005221" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005221" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005221</a>
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<p>In affected members of a family with severe to profound sensorineural hearing loss and no history of nyctalopia (DFNB23; <a href="/entry/609533">609533</a>), <a href="#1" class="mim-tip-reference" title="Ahmed, Z. M., Riazuddin, S., Ahmad, J., Bernstein, S. L., Guo, Y., Sabar, M. F., Sieving, P., Riazuddin, S., Griffith, A. J., Friedman, T. B., Belyantseva, I. A., Wilcox, E. R. <strong>PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23.</strong> Hum. Molec. Genet. 12: 3215-3223, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14570705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14570705</a>] [<a href="https://doi.org/10.1093/hmg/ddg358" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14570705">Ahmed et al. (2003)</a> identified a homozygous 785G-A transition in exon 8 of the PCDH15 gene, resulting in a gly262-to-asp (G262D) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14570705" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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> rs137853003 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853003;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/rs137853003?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=rs137853003" 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=rs137853003" 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=RCV000005222 OR RCV000211736 OR RCV003234893" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005222, RCV000211736, RCV003234893" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005222...</a>
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<p>In a family segregating profound autosomal recessive deafness (DFNB23; <a href="/entry/609533">609533</a>), <a href="#1" class="mim-tip-reference" title="Ahmed, Z. M., Riazuddin, S., Ahmad, J., Bernstein, S. L., Guo, Y., Sabar, M. F., Sieving, P., Riazuddin, S., Griffith, A. J., Friedman, T. B., Belyantseva, I. A., Wilcox, E. R. <strong>PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23.</strong> Hum. Molec. Genet. 12: 3215-3223, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14570705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14570705</a>] [<a href="https://doi.org/10.1093/hmg/ddg358" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14570705">Ahmed et al. (2003)</a> found that affected individuals were homozygous for a 400C-G transversion in exon 5 of the PCDH15 gene, resulting in an arg134-to-gly substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14570705" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs397517451 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397517451;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=rs397517451" 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=rs397517451" 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=RCV000005223 OR RCV000039705 OR RCV000219366 OR RCV000824736 OR RCV001008080" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005223, RCV000039705, RCV000219366, RCV000824736, RCV001008080" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005223...</a>
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<p>In a proband with a diagnosis of Usher syndrome type I (see <a href="/entry/601067">601067</a>), <a href="#14" class="mim-tip-reference" title="Zheng, Q. Y., Yan, D., Ouyang, X. M., Du, L. L., Yu, H., Chang, B., Johnson, K. R., Liu, X. Z. <strong>Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans.</strong> Hum. Molec. Genet. 14: 103-111, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15537665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15537665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15537665[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddi010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15537665">Zheng et al. (2005)</a> detected a 1-bp deletion in exon 2 of the PCDH15 gene (16delT) in compound heterozygosity with a mutation in the CDH23 gene (R3189W; <a href="/entry/605516#0012">605516.0012</a>). The proband's brother, who had normal hearing, carried the 16delT mutation in heterozygosity. The PCDH15 16delT mutation causes a frameshift leading to an altered amino acid sequence from codon 6, followed by a premature termination at codon 11 in the predicted signal peptide of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15537665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 USHER SYNDROME, TYPE IF</strong>
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PCDH15, SER647TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137853004 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853004;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=rs137853004" 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=rs137853004" 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=RCV000005224" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005224" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005224</a>
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<p>In affected members of a consanguineous Pakistani family with Usher syndrome type IF (USH1F; <a href="/entry/602083">602083</a>), <a href="#2" class="mim-tip-reference" title="Ahmed, Z. M., Riazuddin, S., Aye, S., Ali, R. A., Venselaar, H., Anwar, S., Belyantseva, P. P., Qasim, M., Riazuddin, S., Friedman, T. B. <strong>Gene structure and mutant alleles of PCDH15: nonsyndromic deafness DFNB23 and type 1 Usher syndrome.</strong> Hum. Genet. 124: 215-223, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18719945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18719945</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18719945[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/10.1007/s00439-008-0543-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18719945">Ahmed et al. (2008)</a> identified a homozygous 1940C-G transversion in the PCDH15 gene, resulting in a ser647-to-ter (S647X) substitution predicted to truncate the protein in the EC6 domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18719945" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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> rs267606932 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606932;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/rs267606932?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=rs267606932" 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=rs267606932" 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=RCV000005225 OR RCV001851963 OR RCV002513133 OR RCV005042067" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005225, RCV001851963, RCV002513133, RCV005042067" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005225...</a>
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<p>In affected members of a consanguineous family from Newfoundland, Canada, with isolated deafness (DFNB23; <a href="/entry/609533">609533</a>), <a href="#9" class="mim-tip-reference" title="Doucette, L., Merner, N. D., Cooke, S., Ives, E., Galutira, D., Walsh, V., Walsh, T., MacLaren, L., Cater, T., Fernandez, B., Green, J. S., Wilcox, E. R., Shotland, L. I., Li, X. C., Lee, M., King, M.-C., Young, T.-L. <strong>Profound, prelingual nonsyndromic deafness maps to chromosome 10q21 and is caused by a novel missense mutation in the Usher syndrome type IF gene PCDH15.</strong> Europ. J. Hum. Genet. 17: 554-564, 2009. Note: Erratum: Europ. J. Hum. Genet. 17: 1363 only, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19107147/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19107147</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19107147[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/ejhg.2008.231" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19107147">Doucette et al. (2009)</a> identified a homozygous 1583T-A transversion in the PCDH15 gene, resulting in a val528-to-asp (V528D) substitution in the highly conserved fifth ectodomain region. The hearing loss was neurosensory, prelingual, and severe to profound. Ancestors of the family had migrated from England in the early 1800s to settle a fishing 'outport' on Newfoundland's southern coast. Detailed examination of 2 homozygous carriers in middle age showed no evidence of Usher syndrome and no vestibular abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19107147" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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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Ahmed, Z. M., Riazuddin, S., Ahmad, J., Bernstein, S. L., Guo, Y., Sabar, M. F., Sieving, P., Riazuddin, S., Griffith, A. J., Friedman, T. B., Belyantseva, I. A., Wilcox, E. R.
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<strong>PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23.</strong>
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Hum. Molec. Genet. 12: 3215-3223, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14570705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14570705</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14570705" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddg358" target="_blank">Full Text</a>]
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Ahmed, Z. M., Riazuddin, S., Aye, S., Ali, R. A., Venselaar, H., Anwar, S., Belyantseva, P. P., Qasim, M., Riazuddin, S., Friedman, T. B.
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<strong>Gene structure and mutant alleles of PCDH15: nonsyndromic deafness DFNB23 and type 1 Usher syndrome.</strong>
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Hum. Genet. 124: 215-223, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18719945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18719945</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18719945[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=18719945" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s00439-008-0543-3" target="_blank">Full Text</a>]
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<a id="Ahmed2001" class="mim-anchor"></a>
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Ahmed, Z. M., Riazuddin, S., Bernstein, S. L., Ahmed, Z., Khan, S., Griffith, A. J., Morell, R. J., Friedman, T. B., Riazuddin, S., Wilcox, E. R.
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<strong>Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F.</strong>
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Am. J. Hum. Genet. 69: 25-34, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11398101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11398101</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11398101[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=11398101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/321277" target="_blank">Full Text</a>]
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Alagramam, K. N., Miller, N. D., Adappa, N. D., Pitts, D. R., Heaphy, J. C., Yuan, H., Smith, R. J.
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<strong>Promoter, alternative splice forms, and genomic structure of protocadherin 15.</strong>
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Genomics 90: 482-492, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17706913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17706913</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17706913[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=17706913" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ygeno.2007.06.007" target="_blank">Full Text</a>]
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Alagramam, K. N., Murcia, C. L., Kwon, H. Y., Pawlowski, K. S., Wright, C. G., Woychik, R. P.
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<strong>The mouse Ames waltzer hearing-loss mutant is caused by mutation of Pcdh15, a novel protocadherin gene.</strong>
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Nature Genet. 27: 99-102, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11138007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11138007</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11138007" 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/10.1038/83837" target="_blank">Full Text</a>]
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Alagramam, K. N., Yuan, H., Kuehn, M. H., Murcia, C. L., Wayne, S., Srisailpathy, C. R. S., Lowry, R. B., Knaus, R., Van Laer, L., Bernier, F. P., Schwartz, S., Lee, C., Morton, C. C., Mullins, R. F., Ramesh, A., Van Camp, G., Hageman, G. S., Woychik, R. P., Smith, R. J. H.
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<strong>Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F.</strong>
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Hum. Molec. Genet. 10: 1709-1718, 2001. Note: Erratum: Hum. Molec. Genet. 10: 2603 only, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11487575/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11487575</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11487575" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/10.16.1709" target="_blank">Full Text</a>]
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Ben-Yosef, T., Ness, S. L., Madeo, A. C., Bar-Lev, A., Wolfman, J. H., Ahmed, Z. M., Desnick, R. J., Willner, J. P., Avraham, K. B., Ostrer, H., Oddoux, C., Griffith, A. J., Friedman, T. B.
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<strong>A mutation of PCDH15 among Ashkenazi Jews with the type 1 Usher syndrome.</strong>
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New Eng. J. Med. 348: 1664-1670, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12711741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12711741</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12711741" 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/10.1056/NEJMoa021502" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Chong2012" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Chong, J. X., Ouwenga, R., Anderson, R. L., Waggoner, D. J., Ober, C.
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<strong>A population-based study of autosomal-recessive disease-causing mutations in a founder population.</strong>
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Am. J. Hum. Genet. 91: 608-620, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22981120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22981120</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22981120[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=22981120" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2012.08.007" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Doucette2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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|
Doucette, L., Merner, N. D., Cooke, S., Ives, E., Galutira, D., Walsh, V., Walsh, T., MacLaren, L., Cater, T., Fernandez, B., Green, J. S., Wilcox, E. R., Shotland, L. I., Li, X. C., Lee, M., King, M.-C., Young, T.-L.
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<strong>Profound, prelingual nonsyndromic deafness maps to chromosome 10q21 and is caused by a novel missense mutation in the Usher syndrome type IF gene PCDH15.</strong>
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Europ. J. Hum. Genet. 17: 554-564, 2009. Note: Erratum: Europ. J. Hum. Genet. 17: 1363 only, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19107147/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19107147</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19107147[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=19107147" 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/ejhg.2008.231" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Kazmierczak2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Kazmierczak, P., Sakaguchi, H., Tokita, J., Wilson-Kubalek, E. M., Milligan, R. A., Muller, U., Kachar, B.
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|
<strong>Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells.</strong>
|
|
Nature 449: 87-91, 2007.
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|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17805295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17805295</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17805295" 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/nature06091" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Ouyang2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ouyang, X. M., Yan, D., Du, L. L., Hejtmancik, J. F., Jacobson, S. G., Nance, W. E., Li, A. R., Angeli, S., Kaiser, M., Newton, V., Brown, S. D. M., Balkany, T., Liu, X. Z.
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<strong>Characterization of Usher syndrome type I gene mutations in an Usher syndrome patient population.</strong>
|
|
Hum. Genet. 116: 292-299, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15660226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15660226</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15660226" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s00439-004-1227-2" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Rebibo-Sabbah2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Rebibo-Sabbah, A., Nudelman, I., Ahmed, Z. M., Baasov, T., Ben-Yosef, T.
|
|
<strong>In vitro and ex vivo suppression by aminoglycosides of PCDH15 nonsense mutations underlying type 1 Usher syndrome.</strong>
|
|
Hum. Genet. 122: 373-381, 2007.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17653769/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17653769</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17653769" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s00439-007-0410-7" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Sotomayor2012" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sotomayor, M., Weihofen, W. A., Gaudet, R., Corey, D. P.
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<strong>Structure of a force-conveying cadherin bond essential for inner-ear mechanotransduction.</strong>
|
|
Nature 492: 128-132, 2012.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23135401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23135401</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23135401[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=23135401" 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/nature11590" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="Zheng2005" class="mim-anchor"></a>
|
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<div class="">
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<p class="mim-text-font">
|
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Zheng, Q. Y., Yan, D., Ouyang, X. M., Du, L. L., Yu, H., Chang, B., Johnson, K. R., Liu, X. Z.
|
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<strong>Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans.</strong>
|
|
Hum. Molec. Genet. 14: 103-111, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15537665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15537665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15537665[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=15537665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddi010" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
|
|
<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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Ada Hamosh - updated : 2/7/2013
|
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</span>
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</div>
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</div>
|
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
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Ada Hamosh - updated : 1/7/2013<br>Cassandra L. Kniffin - updated : 11/2/2010<br>Cassandra L. Kniffin - updated : 3/30/2009<br>Patricia A. Hartz - updated : 11/7/2007<br>George E. Tiller - updated : 10/31/2007<br>Ada Hamosh - updated : 10/16/2007<br>Victor A. McKusick - updated : 8/12/2005<br>Victor A. McKusick - updated : 3/31/2005<br>Victor A. McKusick - updated : 5/28/2003<br>George E. Tiller - updated : 12/26/2001<br>Victor A. McKusick - updated : 8/15/2001
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
|
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Creation Date:
|
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</span>
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
Victor A. McKusick : 1/2/2001
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
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</span>
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
carol : 02/27/2024
|
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</span>
|
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</div>
|
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</div>
|
|
<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">
|
|
carol : 02/16/2015<br>carol : 8/19/2013<br>alopez : 2/13/2013<br>terry : 2/7/2013<br>alopez : 1/7/2013<br>terry : 1/7/2013<br>joanna : 12/13/2012<br>carol : 2/29/2012<br>carol : 5/5/2011<br>carol : 5/5/2011<br>wwang : 12/7/2010<br>ckniffin : 11/2/2010<br>wwang : 4/10/2009<br>ckniffin : 3/30/2009<br>wwang : 5/21/2008<br>ckniffin : 4/14/2008<br>alopez : 3/18/2008<br>alopez : 3/18/2008<br>mgross : 11/7/2007<br>alopez : 11/6/2007<br>terry : 10/31/2007<br>alopez : 10/18/2007<br>alopez : 10/18/2007<br>terry : 10/16/2007<br>carol : 2/28/2007<br>carol : 8/15/2005<br>carol : 8/15/2005<br>terry : 8/12/2005<br>wwang : 4/6/2005<br>wwang : 4/1/2005<br>terry : 3/31/2005<br>cwells : 6/5/2003<br>terry : 5/28/2003<br>carol : 4/18/2003<br>cwells : 1/4/2002<br>cwells : 12/26/2001<br>cwells : 9/6/2001<br>cwells : 8/23/2001<br>terry : 8/15/2001<br>carol : 1/23/2001<br>mgross : 1/2/2001
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
|
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<h3>
|
|
<span class="mim-font">
|
|
<strong>*</strong> 605514
|
|
</span>
|
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</h3>
|
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</div>
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|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
PROTOCADHERIN 15; PCDH15
|
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|
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</span>
|
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</h3>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: PCDH15</em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
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<p>
|
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<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 10q21.1
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 10:53,802,771-55,627,942 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
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<div>
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<br />
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</div>
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
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</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
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</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
10q21.1
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Deafness, autosomal recessive 23
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
609533
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Usher syndrome, type 1D/F digenic
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
601067
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive; Digenic recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Usher syndrome, type 1F
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
602083
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>Using a mouse Pcdh15 cDNA probe to screen a human genomic P1-derived artificial chromosome (PAC) library, Alagramam et al. (2001, 2001) identified the human PCDH15 gene. The CDH15 cDNA contains an open reading frame (ORF) that encodes 1,955 amino acids (Alagramam et al., 2001). The predicted protein has 11 cadherin repeats, 1 transmembrane domain and a cytoplasmic domain that contains 2 proline-rich regions. By Northern blot analysis, Alagramam et al. (2001) demonstrated PCDH15 expression in human adult brain, lung, and kidney. Expression in human fetal brain was assumed since the human PCDH15 cDNA was obtained by screening a fetal brain library. Additional experiments by RT-PCR and direct sequencing revealed expression in other human adult tissues and human fetal cochlea. Immunohistochemistry detected PCDH15 expression in the inner and outer synaptic layers and the nerve fiber layer in human adult and fetal retinas. Additional reactivity in the region of the outer limiting membrane/photoreceptor cell inner segments was observed in adult but not fetal retina. In human fetal cochlea, Alagramam et al. (2001) detected PCDH15 expression in the supporting cells and outer sulcus cells, as well as in the spiral ganglion. </p><p>Using RT-PCR, Alagramam et al. (2007) identified 2 minor splice variants of mouse Pcdh15, one that skipped exon 2 and another that skipped exons 2 and 4. </p><p>The PCSH15 gene encodes encodes a variety of isoforms with 3 to 11 ectodomains, a transmembrane domain, and a C-terminal cytoplasmic domain (CD). Ahmed et al. (2008) identified 4 additional exons in the PCDH15 gene, which encode 2 novel conserved cytoplasmic domains CD2 and CD3. The amino acid sequences of CD1, CD2, and CD3 are entirely different. PCDH15-CD1 showed a limited pattern of expression and was detected in human testis, retina, and cochlea. PCDH15-CD2 expression was present in the human heart, kidney, thymus, spleen, testis, retina and cochlea. PCDH15-CD3 was widely transcribed and detected in almost all of 18 tissues tested. </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>The human PCDH15 gene contains 33 exons and spans approximately 1.6 Mb of genomic DNA (Ahmed et al., 2001). Only the first 2 exons are situated in the Usher syndrome type IF (USH1F; 602083) critical region defined by one of the Pakistani families studied. The start codon is at 396 bp in exon 2 and the stop codon is at 6,263 bp in exon 33. </p><p>Ahmed et al. (2001) stated that 3 genes are nested in the introns of PCDH15: calcium/calmodulin-dependent protein kinase type II, presumably CAMKG (602123), known to map to 10q22; N-deacetylase/N-sulfotransferase 2 (NDST2; 603268), which maps to 10q22; and plasminogen-activator, urokinase (PLAU; 191840), previously thought to reside in 10q24. </p><p>Alagramam et al. (2007) determined that the promoter region of the PCDH15 gene contains a CpG island, but no TATAA or CAAT sequences. They identified suppressor and enhancer elements within the PCDH15 promoter. </p><p>Ahmed et al. (2008) identified 4 additional exons in the PCDH15 gene, for a total of 39 exons. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Alagramam et al. (2001) mapped the PCDH15 gene to chromosome 10q21-q22. </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>Alagramam et al. (2001) demonstrated PCDH15 expression in both retina and cochlea by RT-PCR and immunohistochemistry. </p><p>Ahmed et al. (2003) localized protocadherin-15 to inner ear hair cell stereocilia and to retinal photoreceptors by immunocytochemistry. The results further strengthened the importance of protocadherin-15 in the morphogenesis and cohesion of stereocilia bundles and retinal photoreceptor cell maintenance or function. </p><p>Kazmierczak et al. (2007) demonstrated that CDH23 (605516) and PCDH15, 2 cadherins linked to inherited forms of deafness in humans, interact to form tip links, extracellular filaments that connect the stereocilia and are thought to gate the mechanoelectrical transduction channel. Immunohistochemical studies using rodent hair cells showed that CDH23 and PCDH15 localized to the upper and lower part of tip links, respectively. The amino termini of the 2 cadherins colocalized on tip link filaments. Biochemical experiments showed that CDH23 homodimers interact in trans with PCDH15 homodimers to form a filament with structural similarity to tip links. Ions that affected tip link integrity and a mutation in PCDH15 that causes a recessive form of deafness (see DFNB23, 609533) disrupted interactions between CDH23 and PCDH15. Kazmierczak et al. (2007) concluded that their studies defined the molecular composition of tip links and provided a conceptual base for exploring the mechanisms of sensory impairment associated with mutations in CDH23 and PCDH15. </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>Biochemical Features</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Crystal Structure</em></strong></p><p>
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Sotomayor et al. (2012) combined crystallography, molecular dynamics simulations, and binding experiments to characterize the protocadherin-15-cadherin-23 (605516) bond. They found a unique cadherin interaction mechanism in which the 2 most N-terminal cadherin repeats (extracellular cadherin repeats 1 and 2) of each protein interact to form an overlapped, antiparallel heterodimer. Simulations predicted that this tip-link bond is mechanically strong enough to resist forces in hair cells. In addition, the complex was shown to become unstable in response to calcium removal owing to increased flexure of calcium-free cadherin repeats. Finally, Sotomayor et al. (2012) used structures and biochemical measurements to study the molecular mechanisms by which deafness mutations disrupt tip-link function. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Usher Syndrome Type IF</em></strong></p><p>
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Ahmed et al. (2001) identified truncating mutations in the PCDH15 gene (605514.0001-605514.0002) in affected members of 2 families segregating Usher syndrome type IF (USH1F; 602083). Northern blot analysis showed expression in the retina, consistent with the pathogenetic role of the PCDH15 gene in retinitis pigmentosa associated with USH1F. </p><p>In cell culture studies, Rebibo-Sabbah et al. (2007) demonstrated that aminoglycosides suppressed translation of several PCDH15 nonsense mutations identified in patients with Usher syndrome type 1F. The aminoglycosides resulted in variable full-length protein levels resulting from partial read-through of the nonsense mutations. Rebibo-Sabbah et al. (2007) postulated that such treatment could potentially delay the progression of retinitis pigmentosa in patients with the disorder. </p><p>Ahmed et al. (2008) identified mutations in the PCDH15 gene in 7 of 12 consanguineous Pakistani families with USH1. Six mutations were novel (see, e.g., 605514.0009). The remaining 5 families showed linkage to chromosome 10q21, but no pathogenic mutations in the PCDH15 gene were identified. </p><p><strong><em>Autosomal Recessive Deafness 23</em></strong></p><p>
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Ahmed et al. (2003) demonstrated that nonsyndromic autosomal recessive deanfess-23 (DFNB23; 609533) is caused by biallelic mutation in the PCDH15 gene (see 605514.0006-605514.0007). They suggested a genotype-phenotype correlation in which hypomorphic alleles of the PCDH15 gene cause nonsyndromic hearing loss, whereas more severe mutations in this gene result in USH1F. </p><p><strong><em>Usher Syndrome Type ID/F</em></strong></p><p>
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Zheng et al. (2005) reported 3 families with Usher syndrome type I (see 601067) in which affected members carried mutations in both CDH23 (605516) and PCDH15, thus supporting a digenic model for some individuals with this phenotype. Based on an animal model, the authors concluded that CDH23 and PCDH15 play an essential long-term role in maintaining the normal organization of the stereocilia bundle. </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>The neuroepithelia of the inner ear contain hair cells that function as mechanoreceptors to transduce sound and motion signals. Mutations affecting these neuroepithelia cause deafness and vestibular dysfunction in humans. Ames waltzer (av) is a recessive mutation in mice that causes deafness and a balance disorder associated with degeneration of inner ear neuroepithelia. Alagramam et al. (2001) identified Pcdh15 as the gene that harbors the av mutation in mice. Cochlear hair cells in the av mutants showed abnormal stereocilia by 10 days after birth. </p><p>Zheng et al. (2005) generated mice that were heterozygous for both Cdh23(v-2J) (605516) and Pcdh15(av-3J) mutations on a uniform C57BL/6J background. Significant levels of hearing loss were detected in these mice when compared to age-matched single heterozygous animals or normal controls, which supported a digenic model of hearing loss. Cytoarchitectural defects in the cochlea of digenic heterozygotes, including degeneration of the stereocilia and a base-apex loss of hair cells and spiral ganglion cells, were consistent with the observed age-related hearing loss of these mice beginning with the high frequencies. The authors noted that while hearing loss was progressive in these animals, humans with heterozygosity for both CDH23 and PCDH15 mutations are congenitally deaf. Zheng et al. (2005) concluded that CDH23 and PCDH15 play an essential long-term role in maintaining the normal organization of the stereocilia bundle. </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>10 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 USHER SYNDROME, TYPE IF</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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PCDH15, IVS27, A-G, -2
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<br />
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SNP: rs1307471318,
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gnomAD: rs1307471318,
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ClinVar: RCV000005215
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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 consanguineous Pakistani family segregating Usher syndrome type IF (USH1F; 602083), Ahmed et al. (2001) found a homozygous IVS27-2A-G splice site mutation in the PCDH15 gene. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 USHER SYNDROME, TYPE IF</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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PCDH15, ARG3TER
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<br />
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SNP: rs137853001,
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gnomAD: rs137853001,
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ClinVar: RCV000005216, RCV000770851, RCV000808283, RCV000824737, RCV005041988
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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 consanguineous Pakistani family, Ahmed et al. (2001) identified a homozygous arg3-to-ter (R3X) missense mutation in the PCDH15 gene as the cause of Usher syndrome type IF (USH1F; 602083). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 USHER SYNDROME, TYPE IF</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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PCDH15, 1-BP DEL, 1471T ({dbSNP rs199469706})
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<br />
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SNP: rs199469706,
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gnomAD: rs199469706,
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ClinVar: RCV000005217, RCV001198734, RCV001381510, RCV003472980, RCV005041989
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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 Hutterite family from Alberta segregating Usher syndrome type IF (USH1F; 602083), Alagramam et al. (2001) identified a homozygous 1-bp deletion of T at nucleotide 1471 in exon 10 of the PCDH15 gene, creating a frameshift and premature stop codon after amino acid 419 in exon 11. </p><p>Among 1,524 Schmiedeleut (S-leut) Hutterites from the United States, Chong et al. (2012) found 38 heterozygotes and no homozygotes for the 1471delT mutation in the PCDH15 gene, for a frequency of 0.025, or 1 in 40. This is a private mutation in the Hutterite population. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 USHER SYNDROME, TYPE IF</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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PCDH15, ARG245TER
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<br />
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SNP: rs111033260,
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gnomAD: rs111033260,
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ClinVar: RCV000005218, RCV000055970, RCV000218809, RCV000269122, RCV000477806, RCV000824735, RCV001004803, RCV001030749, RCV004734497
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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>Ben-Yosef et al. (2003) identified a homozygous arg245-to-ter (R245X) mutation in the PCDH15 gene in cases of Usher syndrome type I (USH1F; 602083) in Ashkenazi Jews. The R245X carrier frequencies (0.79 to 2.48%) were similar to the carrier frequencies of other genetic disorders for which routine screening is performed in this population, such as Tay-Sachs disease (3-4%), Gaucher disease (4-6%), and Canavan disease (1-2%). No R245X carriers were detected among other Jewish or non-Jewish population controls, indicating that this mutation may be unique to Ashkenazi Jews. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0005 USHER SYNDROME, TYPE IF</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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USHER SYNDROME, TYPE ID/F, DIGENIC, 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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PCDH15, 3-BP DEL, 5601AAC
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<br />
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SNP: rs113363047,
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gnomAD: rs113363047,
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ClinVar: RCV000039764, RCV000215699, RCV000514811, RCV001272395, RCV002277128, RCV002490550
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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 from the U.S. with Usher syndrome type IF (USH1F; 602083), Ouyang et al. (2005) identified heterozygosity for a 3-bp deletion (5601-5603delAAC) in exon 33 of the PCDH15 gene, resulting in deletion of threonine-1867. The 3-bp deletion was identified in compound heterozygosity with a PCDH15 missense mutation in another patient with USH1F. The mutation accounted for 2 (33%) of 6 mutant alleles identified by Ouyang et al. (2005) at the PCDH15 locus. </p><p>Zheng et al. (2005) identified 2 patients with a diagnosis of Usher syndrome type I (see 601067) who carried this deletion in heterozygosity, in combination with an additional mutation in the CDH23 gene: a single-basepair deletion (193delC; 605516.0011) and a missense mutation (T1209A; 605516.0013), respectively. The T1209A mutation in the CDH23 gene was later reclassified as a variant of unknown function. </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>.0006 DEAFNESS, AUTOSOMAL RECESSIVE 23</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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PCDH15, GLY262ASP
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<br />
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SNP: rs137853002,
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ClinVar: RCV000005221
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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 affected members of a family with severe to profound sensorineural hearing loss and no history of nyctalopia (DFNB23; 609533), Ahmed et al. (2003) identified a homozygous 785G-A transition in exon 8 of the PCDH15 gene, resulting in a gly262-to-asp (G262D) substitution. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0007 DEAFNESS, AUTOSOMAL RECESSIVE 23</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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PCDH15, ARG134GLY
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<br />
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SNP: rs137853003,
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gnomAD: rs137853003,
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ClinVar: RCV000005222, RCV000211736, RCV003234893
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</span>
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<span class="mim-text-font">
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<p>In a family segregating profound autosomal recessive deafness (DFNB23; 609533), Ahmed et al. (2003) found that affected individuals were homozygous for a 400C-G transversion in exon 5 of the PCDH15 gene, resulting in an arg134-to-gly substitution. </p>
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<h4>
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<span class="mim-font">
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<strong>.0008 USHER SYNDROME, TYPE ID/F, DIGENIC</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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PCDH15, 1-BP DEL, 16T
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<br />
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SNP: rs397517451,
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ClinVar: RCV000005223, RCV000039705, RCV000219366, RCV000824736, RCV001008080
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<p>In a proband with a diagnosis of Usher syndrome type I (see 601067), Zheng et al. (2005) detected a 1-bp deletion in exon 2 of the PCDH15 gene (16delT) in compound heterozygosity with a mutation in the CDH23 gene (R3189W; 605516.0012). The proband's brother, who had normal hearing, carried the 16delT mutation in heterozygosity. The PCDH15 16delT mutation causes a frameshift leading to an altered amino acid sequence from codon 6, followed by a premature termination at codon 11 in the predicted signal peptide of the protein. </p>
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<h4>
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<span class="mim-font">
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<strong>.0009 USHER SYNDROME, TYPE IF</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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PCDH15, SER647TER
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<br />
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SNP: rs137853004,
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ClinVar: RCV000005224
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</span>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a consanguineous Pakistani family with Usher syndrome type IF (USH1F; 602083), Ahmed et al. (2008) identified a homozygous 1940C-G transversion in the PCDH15 gene, resulting in a ser647-to-ter (S647X) substitution predicted to truncate the protein in the EC6 domain. </p>
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</span>
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0010 DEAFNESS, AUTOSOMAL RECESSIVE 23</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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PCDH15, VAL528ASP
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<br />
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SNP: rs267606932,
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gnomAD: rs267606932,
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ClinVar: RCV000005225, RCV001851963, RCV002513133, RCV005042067
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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 affected members of a consanguineous family from Newfoundland, Canada, with isolated deafness (DFNB23; 609533), Doucette et al. (2009) identified a homozygous 1583T-A transversion in the PCDH15 gene, resulting in a val528-to-asp (V528D) substitution in the highly conserved fifth ectodomain region. The hearing loss was neurosensory, prelingual, and severe to profound. Ancestors of the family had migrated from England in the early 1800s to settle a fishing 'outport' on Newfoundland's southern coast. Detailed examination of 2 homozygous carriers in middle age showed no evidence of Usher syndrome and no vestibular abnormalities. </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>REFERENCES</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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<ol>
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<li>
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<p class="mim-text-font">
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Ahmed, Z. M., Riazuddin, S., Ahmad, J., Bernstein, S. L., Guo, Y., Sabar, M. F., Sieving, P., Riazuddin, S., Griffith, A. J., Friedman, T. B., Belyantseva, I. A., Wilcox, E. R.
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<strong>PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23.</strong>
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Hum. Molec. Genet. 12: 3215-3223, 2003.
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[PubMed: 14570705]
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[Full Text: https://doi.org/10.1093/hmg/ddg358]
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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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Ahmed, Z. M., Riazuddin, S., Aye, S., Ali, R. A., Venselaar, H., Anwar, S., Belyantseva, P. P., Qasim, M., Riazuddin, S., Friedman, T. B.
|
|
<strong>Gene structure and mutant alleles of PCDH15: nonsyndromic deafness DFNB23 and type 1 Usher syndrome.</strong>
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Hum. Genet. 124: 215-223, 2008.
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[PubMed: 18719945]
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[Full Text: https://doi.org/10.1007/s00439-008-0543-3]
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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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Ahmed, Z. M., Riazuddin, S., Bernstein, S. L., Ahmed, Z., Khan, S., Griffith, A. J., Morell, R. J., Friedman, T. B., Riazuddin, S., Wilcox, E. R.
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|
<strong>Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F.</strong>
|
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Am. J. Hum. Genet. 69: 25-34, 2001.
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[PubMed: 11398101]
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[Full Text: https://doi.org/10.1086/321277]
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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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Alagramam, K. N., Miller, N. D., Adappa, N. D., Pitts, D. R., Heaphy, J. C., Yuan, H., Smith, R. J.
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<strong>Promoter, alternative splice forms, and genomic structure of protocadherin 15.</strong>
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Genomics 90: 482-492, 2007.
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[PubMed: 17706913]
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[Full Text: https://doi.org/10.1016/j.ygeno.2007.06.007]
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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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Alagramam, K. N., Murcia, C. L., Kwon, H. Y., Pawlowski, K. S., Wright, C. G., Woychik, R. P.
|
|
<strong>The mouse Ames waltzer hearing-loss mutant is caused by mutation of Pcdh15, a novel protocadherin gene.</strong>
|
|
Nature Genet. 27: 99-102, 2001.
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[PubMed: 11138007]
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[Full Text: https://doi.org/10.1038/83837]
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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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Alagramam, K. N., Yuan, H., Kuehn, M. H., Murcia, C. L., Wayne, S., Srisailpathy, C. R. S., Lowry, R. B., Knaus, R., Van Laer, L., Bernier, F. P., Schwartz, S., Lee, C., Morton, C. C., Mullins, R. F., Ramesh, A., Van Camp, G., Hageman, G. S., Woychik, R. P., Smith, R. J. H.
|
|
<strong>Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F.</strong>
|
|
Hum. Molec. Genet. 10: 1709-1718, 2001. Note: Erratum: Hum. Molec. Genet. 10: 2603 only, 2001.
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[PubMed: 11487575]
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[Full Text: https://doi.org/10.1093/hmg/10.16.1709]
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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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Ben-Yosef, T., Ness, S. L., Madeo, A. C., Bar-Lev, A., Wolfman, J. H., Ahmed, Z. M., Desnick, R. J., Willner, J. P., Avraham, K. B., Ostrer, H., Oddoux, C., Griffith, A. J., Friedman, T. B.
|
|
<strong>A mutation of PCDH15 among Ashkenazi Jews with the type 1 Usher syndrome.</strong>
|
|
New Eng. J. Med. 348: 1664-1670, 2003.
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[PubMed: 12711741]
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[Full Text: https://doi.org/10.1056/NEJMoa021502]
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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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Chong, J. X., Ouwenga, R., Anderson, R. L., Waggoner, D. J., Ober, C.
|
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<strong>A population-based study of autosomal-recessive disease-causing mutations in a founder population.</strong>
|
|
Am. J. Hum. Genet. 91: 608-620, 2012.
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[PubMed: 22981120]
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[Full Text: https://doi.org/10.1016/j.ajhg.2012.08.007]
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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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Doucette, L., Merner, N. D., Cooke, S., Ives, E., Galutira, D., Walsh, V., Walsh, T., MacLaren, L., Cater, T., Fernandez, B., Green, J. S., Wilcox, E. R., Shotland, L. I., Li, X. C., Lee, M., King, M.-C., Young, T.-L.
|
|
<strong>Profound, prelingual nonsyndromic deafness maps to chromosome 10q21 and is caused by a novel missense mutation in the Usher syndrome type IF gene PCDH15.</strong>
|
|
Europ. J. Hum. Genet. 17: 554-564, 2009. Note: Erratum: Europ. J. Hum. Genet. 17: 1363 only, 2009.
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[PubMed: 19107147]
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[Full Text: https://doi.org/10.1038/ejhg.2008.231]
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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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Kazmierczak, P., Sakaguchi, H., Tokita, J., Wilson-Kubalek, E. M., Milligan, R. A., Muller, U., Kachar, B.
|
|
<strong>Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells.</strong>
|
|
Nature 449: 87-91, 2007.
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[PubMed: 17805295]
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[Full Text: https://doi.org/10.1038/nature06091]
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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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Ouyang, X. M., Yan, D., Du, L. L., Hejtmancik, J. F., Jacobson, S. G., Nance, W. E., Li, A. R., Angeli, S., Kaiser, M., Newton, V., Brown, S. D. M., Balkany, T., Liu, X. Z.
|
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<strong>Characterization of Usher syndrome type I gene mutations in an Usher syndrome patient population.</strong>
|
|
Hum. Genet. 116: 292-299, 2005.
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[PubMed: 15660226]
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[Full Text: https://doi.org/10.1007/s00439-004-1227-2]
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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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Rebibo-Sabbah, A., Nudelman, I., Ahmed, Z. M., Baasov, T., Ben-Yosef, T.
|
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<strong>In vitro and ex vivo suppression by aminoglycosides of PCDH15 nonsense mutations underlying type 1 Usher syndrome.</strong>
|
|
Hum. Genet. 122: 373-381, 2007.
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[PubMed: 17653769]
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[Full Text: https://doi.org/10.1007/s00439-007-0410-7]
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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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Sotomayor, M., Weihofen, W. A., Gaudet, R., Corey, D. P.
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<strong>Structure of a force-conveying cadherin bond essential for inner-ear mechanotransduction.</strong>
|
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Nature 492: 128-132, 2012.
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[PubMed: 23135401]
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[Full Text: https://doi.org/10.1038/nature11590]
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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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Zheng, Q. Y., Yan, D., Ouyang, X. M., Du, L. L., Yu, H., Chang, B., Johnson, K. R., Liu, X. Z.
|
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<strong>Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans.</strong>
|
|
Hum. Molec. Genet. 14: 103-111, 2005.
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[PubMed: 15537665]
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[Full Text: https://doi.org/10.1093/hmg/ddi010]
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</p>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<div class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Contributors:
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</span>
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</div>
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<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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Ada Hamosh - updated : 2/7/2013<br>Ada Hamosh - updated : 1/7/2013<br>Cassandra L. Kniffin - updated : 11/2/2010<br>Cassandra L. Kniffin - updated : 3/30/2009<br>Patricia A. Hartz - updated : 11/7/2007<br>George E. Tiller - updated : 10/31/2007<br>Ada Hamosh - updated : 10/16/2007<br>Victor A. McKusick - updated : 8/12/2005<br>Victor A. McKusick - updated : 3/31/2005<br>Victor A. McKusick - updated : 5/28/2003<br>George E. Tiller - updated : 12/26/2001<br>Victor A. McKusick - updated : 8/15/2001
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</span>
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</div>
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 1/2/2001
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Edit History:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 02/27/2024<br>carol : 02/16/2015<br>carol : 8/19/2013<br>alopez : 2/13/2013<br>terry : 2/7/2013<br>alopez : 1/7/2013<br>terry : 1/7/2013<br>joanna : 12/13/2012<br>carol : 2/29/2012<br>carol : 5/5/2011<br>carol : 5/5/2011<br>wwang : 12/7/2010<br>ckniffin : 11/2/2010<br>wwang : 4/10/2009<br>ckniffin : 3/30/2009<br>wwang : 5/21/2008<br>ckniffin : 4/14/2008<br>alopez : 3/18/2008<br>alopez : 3/18/2008<br>mgross : 11/7/2007<br>alopez : 11/6/2007<br>terry : 10/31/2007<br>alopez : 10/18/2007<br>alopez : 10/18/2007<br>terry : 10/16/2007<br>carol : 2/28/2007<br>carol : 8/15/2005<br>carol : 8/15/2005<br>terry : 8/12/2005<br>wwang : 4/6/2005<br>wwang : 4/1/2005<br>terry : 3/31/2005<br>cwells : 6/5/2003<br>terry : 5/28/2003<br>carol : 4/18/2003<br>cwells : 1/4/2002<br>cwells : 12/26/2001<br>cwells : 9/6/2001<br>cwells : 8/23/2001<br>terry : 8/15/2001<br>carol : 1/23/2001<br>mgross : 1/2/2001
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