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Entry
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- *605242 - USH1 PROTEIN NETWORK COMPONENT HARMONIN; USH1C
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- OMIM
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<p>
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<span class="h4">*605242</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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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="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/605242">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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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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<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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<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=ENSG00000006611;t=ENST00000005226" 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=10083" 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=605242" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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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=ENSG00000006611;t=ENST00000005226" 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_001297764,NM_005709,NM_153676,NR_123738,XM_011519832,XM_011519834,XM_017017072,XM_017017073,XM_017017074,XM_017017075,XM_047426219,XM_047426220,XM_047426221,XM_047426222" 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_153676" 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=605242" 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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<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=09241&isoform_id=09241_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/USH1C" 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/3170198,3170200,5152288,5231271,10437365,16359185,23342607,41281808,71480164,119588837,119588838,119588839,119588840,158255012,160113087,194374901,663071174,767965244,767965248,957950698,957950701,1034571581,1034571583,1034571586,1034571590,2133013111,2217280739,2217280742,2217280744,2217280746,2462522408,2462522410,2462522412,2462522414,2462522416,2462522418,2462522420,2462522422,2462522424,2462522426" 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/Q9Y6N9" 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 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=10083" 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=ENSG00000006611;t=ENST00000005226" 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=USH1C" 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=USH1C" 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+10083" 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/USH1C" 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:10083" 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/10083" 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=chr11&hgg_gene=ENST00000318024.9&hgg_start=17493900&hgg_end=17544416&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 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:12597" 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:12597" 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=605242[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=605242[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000006611" 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=USH1C" 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=USH1C" 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=USH1C" 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/USH1C" title="Retinal and hearing impairment genetic mutation database USH1C" 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/ush1cmut.htm" title="Mutations of the Harmonin Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Mutations of the Harmonin …</a></div><div style="margin-left: 0.5em;"><a href="http://www.umd.be/USH1C/" title="The UMD USH1C mutations database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">The UMD USH1C mutations da…</a></div><div style="margin-left: 0.5em;"><a href="https://research.cchmc.org/LOVD2/home.php?select_db=USH1C" 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=USH1C&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/PA37226" 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:12597" 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/FBgn0029835.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:1919338" 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/USH1C#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:1919338" 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/10083/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=10083" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-060312-41" 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=USH1C&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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605242
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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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USH1 PROTEIN NETWORK COMPONENT HARMONIN; USH1C
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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USH1C GENE<br />
|
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HARMONIN<br />
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PDZ DOMAIN-CONTAINING PROTEIN, 73-KD; PDZ73
|
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</span>
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=USH1C" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">USH1C</a></em></strong>
|
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</span>
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</p>
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/11/210?start=-3&limit=10&highlight=210">11p15.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr11:17493900-17544416&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'})">11:17,493,900-17,544,416</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>
|
|
<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>
|
|
Location
|
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</th>
|
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<th>
|
|
Phenotype
|
|
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|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=602092,276904" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
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</span>
|
|
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</th>
|
|
<th>
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|
Phenotype <br /> MIM number
|
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</th>
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<th>
|
|
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>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/11/210?start=-3&limit=10&highlight=210">
|
|
11p15.1
|
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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">
|
|
Deafness, autosomal recessive 18A
|
|
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/602092"> 602092 </a>
|
|
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
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|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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|
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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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</td>
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</tr>
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<tr>
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<td>
|
|
<span class="mim-font">
|
|
Usher syndrome, type 1C
|
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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/276904"> 276904 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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|
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</span>
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<p>By serologic expression cloning, <a href="#19" class="mim-tip-reference" title="Scanlan, M. J., Williamson, B., Jungbluth, A., Stockert, E., Arden, K. C., Viars, C. S., Gure, A. O., Gordan, J. D., Chen, Y.-T., Old, L. J. <strong>Isoforms of the human PDZ-73 protein exhibit differential tissue expression.</strong> Biochim. Biophys. Acta 1445: 39-52, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10209257/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10209257</a>] [<a href="https://doi.org/10.1016/s0167-4781(99)00033-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10209257">Scanlan et al. (1999)</a> cloned USH1C, which they designated PDZ73, from a metastatic colon cancer cDNA expression library. The deduced full-length 652-amino acid protein has a calculated molecular mass of about 73 kD. It contains an N-terminal domain followed by 2 PDZ domains; a coiled-coil region with a bipartite nuclear localization signal; a PEST degradation sequence; a third PDZ domain; and a C-terminal domain. PDZ73 also has an N-glycosylation site and 17 putative phosphorylation sites. <a href="#19" class="mim-tip-reference" title="Scanlan, M. J., Williamson, B., Jungbluth, A., Stockert, E., Arden, K. C., Viars, C. S., Gure, A. O., Gordan, J. D., Chen, Y.-T., Old, L. J. <strong>Isoforms of the human PDZ-73 protein exhibit differential tissue expression.</strong> Biochim. Biophys. Acta 1445: 39-52, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10209257/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10209257</a>] [<a href="https://doi.org/10.1016/s0167-4781(99)00033-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10209257">Scanlan et al. (1999)</a> identified several splice variants. One variant encodes a deduced 403-amino acid protein with a calculated molecular mass of about 45 kD. This variant lacks the C-terminal half of the full-length protein, including the PEST sequence, the third PDZ domain, and the C-terminal region. Another variant, which predominates in brain, encodes a putative 328-amino acid protein with a calculated molecular mass of about 37 kD. This variant lacks the N-terminal half of the full-length protein and begins with part of the coiled-coil domain. Northern blot analysis revealed expression of a major 2.4-kb transcript in small intestine, colon, pancreas, kidney, and liver, with lower levels in testis. Although the 2.4-kb transcript was expressed in whole brain, a 1.3-kb transcript, which encodes the 37-kD protein, predominated. Northern blot analysis of specific brain regions detected expression of the 1.3-kb transcript specifically in spinal cord and medulla. RT-PCR detected expression of the transcript corresponding to the 73-kD protein in 13 of 20 samples tested. Expression of the transcript corresponding to the 45-kD protein was detected only in colon, small intestine, testis, brain, and kidney. Other variants showed more restricted expression. Immunohistochemical localization of PDZ73 revealed expression in epithelial cells, specifically at the apical cell border of the small intestine, in proximal and distal cortical tubules of the kidney, and in the cytoplasm of colonic epithelium. <a href="#19" class="mim-tip-reference" title="Scanlan, M. J., Williamson, B., Jungbluth, A., Stockert, E., Arden, K. C., Viars, C. S., Gure, A. O., Gordan, J. D., Chen, Y.-T., Old, L. J. <strong>Isoforms of the human PDZ-73 protein exhibit differential tissue expression.</strong> Biochim. Biophys. Acta 1445: 39-52, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10209257/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10209257</a>] [<a href="https://doi.org/10.1016/s0167-4781(99)00033-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10209257">Scanlan et al. (1999)</a> believed that the protein stained in these sections represents the 45-kD isoform. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10209257" 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>Usher syndrome type I is an autosomal recessive sensory defect involving congenital profound sensorineural deafness, vestibular dysfunction, and blindness due to progressive retinitis pigmentosa. Usher syndrome type IC (USH1C; <a href="/entry/276904">276904</a>) is a subtype mapping to 11p14.3 that had been described in a population of Louisiana Acadians and in a Lebanese family. By studying a subtracted mouse cDNA library derived from inner ear sensory areas, <a href="#23" class="mim-tip-reference" title="Verpy, E., Leibovici, M., Zwaenepoel, I., Liu, X.-Z., Gal, A., Salem, N., Mansour, A., Blanchard, S., Kobayashi, I., Keats, B. J. B., Slim, R., Petit, C. <strong>A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C.</strong> Nature Genet. 26: 51-55, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973247</a>] [<a href="https://doi.org/10.1038/79171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973247">Verpy et al. (2000)</a> demonstrated that the gene responsible for Usher syndrome type IC encodes a PDZ domain-containing protein. They named the protein encoded by the USH1C gene 'harmonin,' from the Greek word 'harmonia,' meaning 'assembling.' They showed that, in the mouse inner ear, only the sensory hair cells express harmonin. The inner ear Ush1c transcripts predicted several harmonin isoforms, some containing an additional coiled-coil domain and a proline- and serine-rich region. Several of these transcripts were absent from the eye. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10973247" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Montell, C. <strong>A PDZ protein ushers in new links.</strong> Nature Genet. 26: 6-7, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973233/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973233</a>] [<a href="https://doi.org/10.1038/79186" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973233">Montell (2000)</a> reviewed the information on the USH1C gene provided by the report of <a href="#23" class="mim-tip-reference" title="Verpy, E., Leibovici, M., Zwaenepoel, I., Liu, X.-Z., Gal, A., Salem, N., Mansour, A., Blanchard, S., Kobayashi, I., Keats, B. J. B., Slim, R., Petit, C. <strong>A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C.</strong> Nature Genet. 26: 51-55, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973247</a>] [<a href="https://doi.org/10.1038/79171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973247">Verpy et al. (2000)</a> and <a href="#4" class="mim-tip-reference" title="Bitner-Glindzicz, M., Lindley, K. J., Rutland, P., Blaydon, D., Smith, V. V., Milla, P. J., Hussain, K., Furth-Lavi, J., Cosgrove, K. E., Shepherd, R. M., Barnes, P. D., O'Brien, R. E., Farndon, P. A., Sowden, J., Liu, X.-Z., Scanlan, M. J., Malcolm, S., Dunne, M. J., Aynsley-Green, A., Glaser, B. <strong>A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C gene.</strong> Nature Genet. 26: 56-60, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973248</a>] [<a href="https://doi.org/10.1038/79178" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973248">Bitner-Glindzicz et al. (2000)</a>. The organization of signaling and cytoskeletal proteins in complexes is coordinated by scaffold proteins composed of multiple protein interaction domains. One such module is the PDZ domain, so-called for the first 3 proteins known to contain it: PSD95 (<a href="/entry/602887">602887</a>), DLG (see <a href="/entry/604090">604090</a>), and ZO1 (<a href="/entry/601009">601009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10973233+10973247+10973248" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By genomic sequence analysis and FISH, <a href="#19" class="mim-tip-reference" title="Scanlan, M. J., Williamson, B., Jungbluth, A., Stockert, E., Arden, K. C., Viars, C. S., Gure, A. O., Gordan, J. D., Chen, Y.-T., Old, L. J. <strong>Isoforms of the human PDZ-73 protein exhibit differential tissue expression.</strong> Biochim. Biophys. Acta 1445: 39-52, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10209257/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10209257</a>] [<a href="https://doi.org/10.1016/s0167-4781(99)00033-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10209257">Scanlan et al. (1999)</a> mapped the PDZ73 gene to chromosome 11p15.4-p15.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10209257" 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="#21" class="mim-tip-reference" title="Siemens, J., Kazmierczak, P., Reynolds, A., Sticker, M., Littlewood-Evans, A., Muller, U. <strong>The Usher syndrome proteins cadherin 23 and harmonin form a complex by means of PDZ-domain interactions.</strong> Proc. Nat. Acad. Sci. 99: 14946-14951, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12407180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12407180</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12407180[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.232579599" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12407180">Siemens et al. (2002)</a> showed that harmonin and CDH23 (<a href="/entry/605516">605516</a>), another protein that is the site of mutations causing Usher syndrome, form a protein complex. Two PDZ domains in harmonin interact with 2 complementary binding surfaces in the CDH23 cytoplasmic domain. One of the binding surfaces is disrupted by sequences encoded by an alternatively spliced CDH23 exon that is expressed in the ear, but not in the retina. In the ear, CDH23 and harmonin are expressed in the stereocilia of hair cells, and in the retina within the photoreceptor cell layer. Because Cdh23-deficient mice have splayed stereocilia, <a href="#21" class="mim-tip-reference" title="Siemens, J., Kazmierczak, P., Reynolds, A., Sticker, M., Littlewood-Evans, A., Muller, U. <strong>The Usher syndrome proteins cadherin 23 and harmonin form a complex by means of PDZ-domain interactions.</strong> Proc. Nat. Acad. Sci. 99: 14946-14951, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12407180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12407180</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12407180[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.232579599" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12407180">Siemens et al. (2002)</a> suggested that CDH23 and harmonin are part of a transmembrane complex that connects stereocilia into a bundle, and that defects in the formation of this complex may disrupt stereocilia bundles and cause deafness in patients with Usher syndrome type I. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12407180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Boeda, B., El-Amraoui, A., Bahloul, A., Goodyear, R., Daviet, L., Blanchard, S., Perfettini, I., Fath, K. R., Shorte, S., Reiners, J., Houdusse, A., Legrain, P., Wolfrum, U., Richardson, G., Petit, C. <strong>Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle.</strong> EMBO J. 21: 6689-6699, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12485990/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12485990</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12485990[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/emboj/cdf689" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12485990">Boeda et al. (2002)</a> noted that defects in the MYO7A (<a href="/entry/276903">276903</a>), CDH23, and harmonin genes result in forms of Usher syndrome. They observed severely disorganized hair bundles in shaker-1 mice, which carry a mutation in the Myo7a gene. Immunohistochemical analysis of differentiating hair cells indicated that Cdh23 was distributed normally, but harmonin b was not. Using human and mouse cDNA constructs and cells, they confirmed interaction between harmonin and CDH23 in vitro and in vivo. They also provided evidence that harmonin b anchors CDH23 to the stereocilia microfilaments and interacts directly with MYO7A, which conveys harmonin b along the actin core of the developing stereocilia. <a href="#6" class="mim-tip-reference" title="Boeda, B., El-Amraoui, A., Bahloul, A., Goodyear, R., Daviet, L., Blanchard, S., Perfettini, I., Fath, K. R., Shorte, S., Reiners, J., Houdusse, A., Legrain, P., Wolfrum, U., Richardson, G., Petit, C. <strong>Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle.</strong> EMBO J. 21: 6689-6699, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12485990/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12485990</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12485990[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/emboj/cdf689" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12485990">Boeda et al. (2002)</a> proposed that the shaping of the hair bundle relies on a functional unit composed of MYO7A, harmonin b, and CDH23, and that the interaction of these proteins ensures the cohesion of the stereocilia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12485990" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By using cotransfection and immunolocalization techniques, <a href="#1" class="mim-tip-reference" title="Adato, A., Michel, V., Kikkawa, Y., Reiners, J., Alagramam, K. N., Weil, D., Yonekawa, H., Wolfrum, U., El-Amraoui, A., Petit, C. <strong>Interactions in the network of Usher syndrome type 1 proteins.</strong> Hum. Molec. Genet. 14: 347-356, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15590703/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15590703</a>] [<a href="https://doi.org/10.1093/hmg/ddi031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15590703">Adato et al. (2005)</a> documented the interaction between SANS (USH1G; <a href="/entry/607696">607696</a>) and harmonin, and also determined that SANS binds to myosin VIIa. The authors noted that harmonin b could interact with all harmonin isoforms and that harmonin bound to protocadherin-15 (PCDH15; <a href="/entry/605514">605514</a>). <a href="#1" class="mim-tip-reference" title="Adato, A., Michel, V., Kikkawa, Y., Reiners, J., Alagramam, K. N., Weil, D., Yonekawa, H., Wolfrum, U., El-Amraoui, A., Petit, C. <strong>Interactions in the network of Usher syndrome type 1 proteins.</strong> Hum. Molec. Genet. 14: 347-356, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15590703/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15590703</a>] [<a href="https://doi.org/10.1093/hmg/ddi031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15590703">Adato et al. (2005)</a> proposed that, via its binding to myosin VIIa and/or harmonin, SANS controls the hair bundle cohesion and proper development by regulating the traffic of USH1 proteins en route to the stereocilia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15590703" 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="Reiners, J., van Wijk, E., Marker, T., Zimmermann, U., Jurgens, K., Brinke, H., Overlack, N., Roepman, R., Knipper, M., Kremer, H., Wolfrum, U. <strong>Scaffold protein harmonin (USH1C) provides molecular links between Usher syndrome type 1 and type 2.</strong> Hum. Molec. Genet. 14: 3933-3943, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16301216/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16301216</a>] [<a href="https://doi.org/10.1093/hmg/ddi417" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16301216">Reiners et al. (2005)</a> demonstrated a molecular interaction between the scaffold protein harmonin, the USH2A protein usherin (<a href="/entry/608400">608400</a>), VLGR1 (USH2C; <a href="/entry/602851">602851</a>), and NBC3 (SLC4A7; <a href="/entry/603353">603353</a>). The authors pinpointed these interactions to the PDZ1 domain of harmonin and the PDZ-binding motifs at the C termini of the USH2 proteins and NBC3. USH2A, VLGR1, and NBC3 are coexpressed with the USH1 protein harmonin in the synaptic terminals of both retinal photoreceptors and inner ear hair cells. In hair cells, these USH proteins are also localized in the signal uptaking stereocilia. The authors concluded that the USH2 proteins and NBC3 are partners in the supramolecular USH protein network in the retina and inner ear. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16301216" 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="Bahloul, A., Michel, V., Hardelin, J.-P., Nouaille, S., Hoos, S., Houdusse, A., England, P., Petit, C. <strong>Cadherin-23, myosin VIIa and harmonin, encoded by Usher syndrome type I genes, for a ternary complex and interact with membrane phospholipids.</strong> Hum. Molec. Genet. 19: 3557-3565, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20639393/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20639393</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20639393[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/ddq271" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20639393">Bahloul et al. (2010)</a> found that both isoforms of mouse Cdh23 bound directly to the harmonin A isoform and to the tail of myosin-7a. The 3 proteins formed a complex that interacted with phosphatidylinositol 4,5-bisphosphate in synthetic liposomes. Knockout of Cdh23 in mice resulted in loss of harmonin from the apex of hair bundles in the organ of Corti and caused redistribution of a weakened myosin-7a signal along stereocilia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20639393" 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 patients with Usher syndrome type IC, <a href="#23" class="mim-tip-reference" title="Verpy, E., Leibovici, M., Zwaenepoel, I., Liu, X.-Z., Gal, A., Salem, N., Mansour, A., Blanchard, S., Kobayashi, I., Keats, B. J. B., Slim, R., Petit, C. <strong>A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C.</strong> Nature Genet. 26: 51-55, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973247</a>] [<a href="https://doi.org/10.1038/79171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973247">Verpy et al. (2000)</a> found a splice site mutation (<a href="#0001">605242.0001</a>), a frameshift mutation (<a href="#0002">605242.0002</a>), and the expansion of an intronic variable number of tandem repeats (VNTRs) (<a href="#0003">605242.0003</a>) in the USH1C gene. <a href="#23" class="mim-tip-reference" title="Verpy, E., Leibovici, M., Zwaenepoel, I., Liu, X.-Z., Gal, A., Salem, N., Mansour, A., Blanchard, S., Kobayashi, I., Keats, B. J. B., Slim, R., Petit, C. <strong>A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C.</strong> Nature Genet. 26: 51-55, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973247</a>] [<a href="https://doi.org/10.1038/79171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973247">Verpy et al. (2000)</a> proposed that mutation in the USH1C gene also underlies the form of nonsyndromic autosomal recessive neurosensory deafness designated DFNB18 (DFNB18A; <a href="/entry/602092">602092</a>), which maps to the same region of 11p. <a href="#13" class="mim-tip-reference" title="Ouyang, X. M., Xia, X. J., Verpy, E., Du, L. L., Pandya, A., Petit, C., Balkany, T., Nance, W. E., Liu, X. Z. <strong>Mutations in the alternatively spliced exons of USH1C cause non-syndromic recessive deafness.</strong> Hum. Genet. 111: 26-30, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12136232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12136232</a>] [<a href="https://doi.org/10.1007/s00439-002-0736-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12136232">Ouyang et al. (2002)</a> indeed found a family with profound deafness without retinitis pigmentosa due to a mutation in the USH1C gene (<a href="#0009">605242.0009</a>). <a href="#2" class="mim-tip-reference" title="Ahmed, Z. M., Smith, T. N., Riazuddin, S., Makishima, T., Ghosh, M., Bokhari, S., Menon, P. S. N., Deshmukh, D., Griffith, A. J., Riazuddin, S., Friedman, T. B., Wilcox, E. R. <strong>Nonsyndromic recessive deafness DFNB18 and Usher syndrome type IC are allelic mutations of USHIC.</strong> Hum. Genet. 110: 527-531, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12107438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12107438</a>] [<a href="https://doi.org/10.1007/s00439-002-0732-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12107438">Ahmed et al. (2002)</a> identified a splice site mutation in intron 12 of the harmonin gene (<a href="#0008">605242.0008</a>) in a family with DFNB18A. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12107438+10973247+12136232" 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="Bitner-Glindzicz, M., Lindley, K. J., Rutland, P., Blaydon, D., Smith, V. V., Milla, P. J., Hussain, K., Furth-Lavi, J., Cosgrove, K. E., Shepherd, R. M., Barnes, P. D., O'Brien, R. E., Farndon, P. A., Sowden, J., Liu, X.-Z., Scanlan, M. J., Malcolm, S., Dunne, M. J., Aynsley-Green, A., Glaser, B. <strong>A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C gene.</strong> Nature Genet. 26: 56-60, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973248</a>] [<a href="https://doi.org/10.1038/79178" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973248">Bitner-Glindzicz et al. (2000)</a> identified a partial deletion of the USH1C gene in a contiguous gene deletion syndrome (<a href="/entry/606528">606528</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10973248" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Ouyang, X. M., Hejtmancik, J. F., Jacobson, S. G., Xia, X. J., Li, A., Du, L. L., Newton, V., Kaiser, M., Balkany, T., Nance, W. E., Liu, X.-Z. <strong>USH1C: a rare cause of USH1 in a non-Acadian population and a founder effect of the Acadian allele.</strong> Clin. Genet. 63: 150-153, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12630964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12630964</a>] [<a href="https://doi.org/10.1046/j.0009-9163.2002.00004.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12630964">Ouyang et al. (2003)</a> determined the frequency of USH1C mutations as a cause of Usher syndrome type I by studying 128 probands, 7 from Acadian and 121 from non-Acadian populations. All 7 Acadian Usher syndrome type I patients were found to be homozygous for both the 216G-A mutation (<a href="#0004">605242.0004</a>) and the 9-repeat VNTR (<a href="#0003">605242.0003</a>), which the authors referred to as the Acadian alleles, confirming previous evidence for a founder effect by haplotype analysis. However, USH1C mutations were identified in only 2 of the non-Acadian probands (1.65%): 1 from Pakistan who was homozygous for a 1-bp insertion (238_239insC; <a href="#0002">605242.0002</a>) and 1 from Canada who was homozygous for the Acadian alleles. The affected haplotypes in the Canadian patient in comparison with the Acadian patients yielded evidence for a founder effect. <a href="#12" class="mim-tip-reference" title="Ouyang, X. M., Hejtmancik, J. F., Jacobson, S. G., Xia, X. J., Li, A., Du, L. L., Newton, V., Kaiser, M., Balkany, T., Nance, W. E., Liu, X.-Z. <strong>USH1C: a rare cause of USH1 in a non-Acadian population and a founder effect of the Acadian allele.</strong> Clin. Genet. 63: 150-153, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12630964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12630964</a>] [<a href="https://doi.org/10.1046/j.0009-9163.2002.00004.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12630964">Ouyang et al. (2003)</a> suggested that Usher syndrome type IC is a relatively rare form of Usher syndrome type I in non-Acadian populations, and that the high frequency of the 238_239insC mutation in the study of <a href="#24" class="mim-tip-reference" title="Zwaenepoel, I., Verpy, E., Blanchard, S., Meins, M., Apfelstedt-Sylla, E., Gal, A., Petit, C. <strong>Identification of three novel mutations in the USH1C gene and detection of thirty-one polymorphisms used for haplotype analysis.</strong> Hum. Mutat. 17: 34-41, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11139240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11139240</a>] [<a href="https://doi.org/10.1002/1098-1004(2001)17:1<34::AID-HUMU4>3.0.CO;2-O" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11139240">Zwaenepoel et al. (2001)</a> in Germany may reflect a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12630964+11139240" 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 the U.K., <a href="#5" class="mim-tip-reference" title="Blaydon, D. C., Mueller, R. F., Hutchin, T. P., Leroy, B. P., Bhattacharya, S. S., Bird, A. C., Malcolm, S., Bitner-Glindzicz, M. <strong>The contribution of USH1C mutations to syndromic and non-syndromic deafness in the UK.</strong> Clin. Genet. 63: 303-307, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12702164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12702164</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2003.00058.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12702164">Blaydon et al. (2003)</a> found no mutations in the USH1C gene in patients with nonsyndromic deafness but found more instances of USH1C mutations in Usher syndrome type I than had previously been thought to occur. The 238_239insC mutation (<a href="#0002">605242.0002</a>) was found in homozygous state in an Usher syndrome type I patient of Greek Cypriot origin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12702164" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a metaanalysis of gross insertions causing human genetic disease based on sequence data in the Human Gene Mutation Database, <a href="#7" class="mim-tip-reference" title="Chen, J.-M., Chuzhanova, N., Stenson, P. D., Ferec, C., Cooper, D. N. <strong>Meta-analysis of gross insertions causing human genetic disease: novel mutational mechanisms and the role of replication slippage.</strong> Hum. Mutat. 25: 207-221, 2005. Note: Erratum: Hum. Mutat. 25: 318 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15643617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15643617</a>] [<a href="https://doi.org/10.1002/humu.20133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15643617">Chen et al. (2005)</a> found an example of a 36-bp insertion in exon 9 of the USH1C gene, the origin of which was the mitochondrial chromosome. <a href="#22" class="mim-tip-reference" title="Turner, C., Killoran, C., Thomas, N. S. T., Rosenberg, M., Chuzhanova, N. A., Johnston, J., Kemel, Y., Cooper, D. N., Biesecker, L. G. <strong>Human genetic disease caused by de novo mitochondrial-nuclear DNA transfer.</strong> Hum. Genet. 112: 303-309, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12545275/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12545275</a>] [<a href="https://doi.org/10.1007/s00439-002-0892-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12545275">Turner et al. (2003)</a> reported a 72-bp insertion of mitochondrial DNA in the GLI3 gene (<a href="/entry/165240">165240</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12545275+15643617" 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 2 sibs from a Caucasian British family with hearing loss diagnosed at 4 years of age and retinitis pigmentosa of the 'sector' type, who were negative for pathogenic changes in 7 other Usher-associated genes, <a href="#16" class="mim-tip-reference" title="Saihan, Z., Stabej, P. L. Q., Robson, A. G., Rangesh, N., Holder, G. E., Moore, A. T., Steel, K. P., Luxon, L. M., Bitner-Glindzicz, M., Webster, A. R. <strong>Mutations in the USH1C gene associated with sector retinitis pigmentosa and hearing loss.</strong> Retina 31: 1708-1716, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21487335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21487335</a>] [<a href="https://doi.org/10.1097/IAE.0b013e31820d3fd1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21487335">Saihan et al. (2011)</a> identified compound heterozygosity for a missense mutation (R103H; <a href="#0011">605242.0011</a>) and a splice site mutation (<a href="#0012">605242.0012</a>) in the USH1C gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21487335" 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 12 patients from 8 Israeli families of Yemenite Jewish origin with retinitis pigmentosa and late-onset hearing loss, <a href="#9" class="mim-tip-reference" title="Khateb, S., Zelinger, L., Ben-Yosef, T., Merin, S., Crystal-Shalit, O., Gross, M., Banin, E., Sharon, D. <strong>Exome sequencing identifies a founder frameshift mutation in an alternative exon of USH1C as the cause of autosomal recessive retinitis pigmentosa with late-onset hearing loss.</strong> PLoS One 7: e51566, 2012. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23251578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23251578</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23251578[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/10.1371/journal.pone.0051566" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23251578">Khateb et al. (2012)</a> identified homozygosity for a 1-bp deletion in the USH1C gene (1220delG; <a href="#0013">605242.0013</a>). A carrier frequency of 0.008 for the 1220G mutation was found in the Israeli Yemenite Jewish population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23251578" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#8" class="mim-tip-reference" title="Johnson, K. R., Gagnon, L. H., Webb, L. S., Peters, L. L., Hawes, N. L., Chang, B., Zheng, Q. Y. <strong>Mouse models of USH1C and DFNB18: phenotypic and molecular analyses of two new spontaneous mutations of the Ush1c gene.</strong> Hum. Molec. Genet. 12: 3075-3086, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14519688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14519688</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14519688[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/ddg332" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14519688">Johnson et al. (2003)</a> mapped 2 recessive, allelic murine mutations causing circling behavior and deafness to the same region on chromosome 7. The 'deaf circler' (dfcr) mutation is a 12.8-kb intragenic deletion in Ush1c that eliminates 3 constitutive and 5 alternatively spliced exons. The 'deaf circler-2 Jackson' (dfcr-2J) mutation is a 1-bp deletion in an alternatively spliced exon of Ush1c that creates a transcriptional frameshift, changing 38 amino acid codons before introducing a premature stop codon. Both mutations cause congenital deafness and severe balance deficits due to inner ear dysfunction. The stereocilia of cochlear hair cells are disorganized and splayed in mutant mice, with subsequent degeneration of the hair cells and spiral ganglion cells. Harmonin had been shown to bind, by means of its PDZ-domains, with the products of other Usher syndrome genes, including Myo7a, Cdh23, and Sans. The complexes formed by these protein interactions are thought to be essential for maintaining the integrity of hair cell stereocilia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14519688" 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>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>13 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=605242[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1480243085 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1480243085;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/rs1480243085?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=rs1480243085" 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=rs1480243085" 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=RCV000005447 OR RCV001003246 OR RCV001383896 OR RCV003466820 OR RCV004814836 OR RCV005041990" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005447, RCV001003246, RCV001383896, RCV003466820, RCV004814836, RCV005041990" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005447...</a>
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<p>In patients with Usher syndrome type IC (<a href="/entry/276904">276904</a>) in a consanguineous Lebanese family (<a href="#17" class="mim-tip-reference" title="Saouda, M., Mansour, A., Moglabey, Y. B., Zir, E. E., Mustapha, M., Chaib, H., Nehme, A., Megarbane, A., Loiselet, J., Petit, C., Slim, R. <strong>The Usher syndrome in the Lebanese population and further refinement of the USH2A candidate region.</strong> Hum. Genet. 103: 193-198, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9760205/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9760205</a>] [<a href="https://doi.org/10.1007/s004390050806" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9760205">Saouda et al., 1998</a>), <a href="#23" class="mim-tip-reference" title="Verpy, E., Leibovici, M., Zwaenepoel, I., Liu, X.-Z., Gal, A., Salem, N., Mansour, A., Blanchard, S., Kobayashi, I., Keats, B. J. B., Slim, R., Petit, C. <strong>A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C.</strong> Nature Genet. 26: 51-55, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973247</a>] [<a href="https://doi.org/10.1038/79171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973247">Verpy et al. (2000)</a> identified deletion of 1 nucleotide at the intron 5/exon 6 junction of the USH1C gene. This mutation (IVS5-2delA) affected the invariant A of the acceptor splice site AG dinucleotide and was therefore expected to lead to aberrant splicing, such as a skipping of the 25-bp exon 6, creating a premature stop codon in exon 8. The same mutation was found in homozygous state in 8 Usher syndrome type I affected children from an unrelated Lebanese family. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9760205+10973247" 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> rs397515359 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397515359;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/rs397515359?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=rs397515359" 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=rs397515359" 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=RCV000005448 OR RCV000213574 OR RCV000505081 OR RCV000727619 OR RCV000787893 OR RCV000824775 OR RCV000984011 OR RCV001073457 OR RCV001291493 OR RCV004755713 OR RCV005003337" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005448, RCV000213574, RCV000505081, RCV000727619, RCV000787893, RCV000824775, RCV000984011, RCV001073457, RCV001291493, RCV004755713, RCV005003337" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005448...</a>
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<p>In a consanguineous Muslim family living in England with Usher syndrome type IC (<a href="/entry/276904">276904</a>) with 3 affected children, <a href="#23" class="mim-tip-reference" title="Verpy, E., Leibovici, M., Zwaenepoel, I., Liu, X.-Z., Gal, A., Salem, N., Mansour, A., Blanchard, S., Kobayashi, I., Keats, B. J. B., Slim, R., Petit, C. <strong>A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C.</strong> Nature Genet. 26: 51-55, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973247</a>] [<a href="https://doi.org/10.1038/79171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973247">Verpy et al. (2000)</a> found insertion of a C within a stretch of 6 consecutive cytosines (nucleotide positions 233-238) in exon 3 of the USH1C gene. This insertion (238_239insC) was expected to result in translation of 68 out-of-frame amino acids and protein termination at codon 148 in exon 5. <a href="#23" class="mim-tip-reference" title="Verpy, E., Leibovici, M., Zwaenepoel, I., Liu, X.-Z., Gal, A., Salem, N., Mansour, A., Blanchard, S., Kobayashi, I., Keats, B. J. B., Slim, R., Petit, C. <strong>A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C.</strong> Nature Genet. 26: 51-55, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973247</a>] [<a href="https://doi.org/10.1038/79171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973247">Verpy et al. (2000)</a> found the same 238_239insC mutation in 4 patients from Germany (all of European descent) with Usher syndrome but no detected mutations of MYO7A (<a href="/entry/276903">276903</a>). <a href="#4" class="mim-tip-reference" title="Bitner-Glindzicz, M., Lindley, K. J., Rutland, P., Blaydon, D., Smith, V. V., Milla, P. J., Hussain, K., Furth-Lavi, J., Cosgrove, K. E., Shepherd, R. M., Barnes, P. D., O'Brien, R. E., Farndon, P. A., Sowden, J., Liu, X.-Z., Scanlan, M. J., Malcolm, S., Dunne, M. J., Aynsley-Green, A., Glaser, B. <strong>A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C gene.</strong> Nature Genet. 26: 56-60, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973248</a>] [<a href="https://doi.org/10.1038/79178" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973248">Bitner-Glindzicz et al. (2000)</a> likewise found this insertion in a Pakistani family. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10973247+10973248" 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="#24" class="mim-tip-reference" title="Zwaenepoel, I., Verpy, E., Blanchard, S., Meins, M., Apfelstedt-Sylla, E., Gal, A., Petit, C. <strong>Identification of three novel mutations in the USH1C gene and detection of thirty-one polymorphisms used for haplotype analysis.</strong> Hum. Mutat. 17: 34-41, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11139240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11139240</a>] [<a href="https://doi.org/10.1002/1098-1004(2001)17:1<34::AID-HUMU4>3.0.CO;2-O" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11139240">Zwaenepoel et al. (2001)</a> found that all carriers of the 238_239insC mutation share a common haplotype. A different common haplotype was found in 2 carriers of the IVS1+1G-T mutation (<a href="#0005">605242.0005</a>). <a href="#24" class="mim-tip-reference" title="Zwaenepoel, I., Verpy, E., Blanchard, S., Meins, M., Apfelstedt-Sylla, E., Gal, A., Petit, C. <strong>Identification of three novel mutations in the USH1C gene and detection of thirty-one polymorphisms used for haplotype analysis.</strong> Hum. Mutat. 17: 34-41, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11139240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11139240</a>] [<a href="https://doi.org/10.1002/1098-1004(2001)17:1<34::AID-HUMU4>3.0.CO;2-O" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11139240">Zwaenepoel et al. (2001)</a> proposed a founder effect of these 2 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11139240" 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">rs55983148 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs55983148;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=rs55983148" 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=rs55983148" 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=RCV000005449 OR RCV000218261" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005449, RCV000218261" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005449...</a>
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<p>In Louisiana-Acadian patients with Usher syndrome type IC (<a href="/entry/276904">276904</a>), <a href="#23" class="mim-tip-reference" title="Verpy, E., Leibovici, M., Zwaenepoel, I., Liu, X.-Z., Gal, A., Salem, N., Mansour, A., Blanchard, S., Kobayashi, I., Keats, B. J. B., Slim, R., Petit, C. <strong>A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C.</strong> Nature Genet. 26: 51-55, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973247</a>] [<a href="https://doi.org/10.1038/79171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973247">Verpy et al. (2000)</a> found no mutation in the coding sequence of the harmonin gene; however, they detected an expansion of a variable number of tandem repeats (VNTR) of a 45-bp element in intron 5 of the USH1C gene. They detected no control individuals with 2 alleles bearing more than 6 repeats. In all but 1 of 11 Acadian patients, they found an allele with 9 tandem repeats in the homozygous state. These 10 individuals were from 7 families. The remaining Acadian patient carried the 9 tandem repeats on 1 chromosome and the 238_239insC mutation (<a href="#0002">605242.0002</a>) on the other. <a href="#23" class="mim-tip-reference" title="Verpy, E., Leibovici, M., Zwaenepoel, I., Liu, X.-Z., Gal, A., Salem, N., Mansour, A., Blanchard, S., Kobayashi, I., Keats, B. J. B., Slim, R., Petit, C. <strong>A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C.</strong> Nature Genet. 26: 51-55, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973247</a>] [<a href="https://doi.org/10.1038/79171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973247">Verpy et al. (2000)</a> proposed that this 405-bp intronic sequence composed of 9 tandem repeats was responsible for the disease in the Acadian population of Louisiana. The repeat expansion was predicted to inhibit transcription, as shown for the expanded GAA triplet repeats from intron 1 of the Friedreich ataxia gene (<a href="/entry/229300">229300</a>). Alternatively, it may cause abnormal posttranscriptional processing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10973247" 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="#18" class="mim-tip-reference" title="Savas, S., Frischhertz, B., Pelias, M. Z., Batzer, M. A., Deininger, P. L., Keats, B. J. B. <strong>The USH1C 216G-A mutation and the 9-repeat VNTR(t,t) allele are in complete linkage disequilibrium in the Acadian population.</strong> Hum. Genet. 110: 95-97, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11810303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11810303</a>] [<a href="https://doi.org/10.1007/s00439-001-0653-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11810303">Savas et al. (2002)</a> found that 43 of 44 Acadian patients with Usher syndrome were homozygous for both a 216G-A mutation (<a href="#0004">605242.0004</a>) and the 45-bp VNTR polymorphism in the USH1C gene. The remaining Acadian patient was a compound heterozygote for the 216G-A allele (with the intron 5 VNTR in cis) and 238_239insC (<a href="#0002">605242.0002</a>), an USH1C mutation found in other populations. The findings demonstrated that the VNTR polymorphism, designated 9VNTR(t,t), had complete linkage disequilibrium with the 216G-A mutation in the Acadian population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11810303" 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> rs151045328 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs151045328;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/rs151045328?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=rs151045328" 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=rs151045328" 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=RCV000005450 OR RCV000220605 OR RCV000504855 OR RCV000724016 OR RCV000763237 OR RCV000824776 OR RCV000984012 OR RCV004755714" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005450, RCV000220605, RCV000504855, RCV000724016, RCV000763237, RCV000824776, RCV000984012, RCV004755714" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005450...</a>
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<p>In cell lines from an Acadian family with Usher syndrome type IC (<a href="/entry/276904">276904</a>), <a href="#4" class="mim-tip-reference" title="Bitner-Glindzicz, M., Lindley, K. J., Rutland, P., Blaydon, D., Smith, V. V., Milla, P. J., Hussain, K., Furth-Lavi, J., Cosgrove, K. E., Shepherd, R. M., Barnes, P. D., O'Brien, R. E., Farndon, P. A., Sowden, J., Liu, X.-Z., Scanlan, M. J., Malcolm, S., Dunne, M. J., Aynsley-Green, A., Glaser, B. <strong>A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C gene.</strong> Nature Genet. 26: 56-60, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973248</a>] [<a href="https://doi.org/10.1038/79178" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973248">Bitner-Glindzicz et al. (2000)</a> found a G-to-A change at position 216 of the USH1C cDNA. The affected individual was homozygous for the substitution and the parents were heterozygous. Although this substitution did not change an amino acid, examination of the sequence suggested that it might create a new splice site. Analysis of USH1C lymphoblastoid cDNA from the Acadian family showed that the affected individual produced a shortened RT-PCR product. Sequencing revealed a 39-bp deletion, consistent with the creation of a new splice site within exon 3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10973248" 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="#18" class="mim-tip-reference" title="Savas, S., Frischhertz, B., Pelias, M. Z., Batzer, M. A., Deininger, P. L., Keats, B. J. B. <strong>The USH1C 216G-A mutation and the 9-repeat VNTR(t,t) allele are in complete linkage disequilibrium in the Acadian population.</strong> Hum. Genet. 110: 95-97, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11810303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11810303</a>] [<a href="https://doi.org/10.1007/s00439-001-0653-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11810303">Savas et al. (2002)</a> found that 43 of 44 Acadian patients with Usher syndrome were homozygous for both the 216G-A mutation and for the 45-bp VNTR polymorphism in intron 5 (<a href="#0003">605242.0003</a>) of the USH1C gene. The remaining Acadian patient was a compound heterozygote for the 216G-A allele (with the intron 5 VNTR in cis) and 238_239insC (<a href="#0002">605242.0002</a>), an USH1C mutation found in other populations. The findings demonstrated that the VNTR polymorphism, designated 9VNTR(t,t), had complete linkage disequilibrium with the 216G-A mutation in the Acadian population. Among 82 Acadian controls, 1 was heterozygous for 216G-A/9VNTR(t,t). The 238_239insC mutation was not found in Acadian controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11810303" 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> rs1403777293 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1403777293;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/rs1403777293?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=rs1403777293" 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=rs1403777293" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>A complete USH1C mutation screen in 4 carriers of the 238_239insC mutation (<a href="#0002">605242.0002</a>) resulted in the detection of the second mutation in all of the carriers, and the identification of 3 novel mutations of which 2 were splice site mutations (IVS1+1G-T; IVS5+1G-A, <a href="#0006">605242.0006</a>) and the other a nonsense mutation (R31X; <a href="#0007">605242.0007</a>) (<a href="#24" class="mim-tip-reference" title="Zwaenepoel, I., Verpy, E., Blanchard, S., Meins, M., Apfelstedt-Sylla, E., Gal, A., Petit, C. <strong>Identification of three novel mutations in the USH1C gene and detection of thirty-one polymorphisms used for haplotype analysis.</strong> Hum. Mutat. 17: 34-41, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11139240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11139240</a>] [<a href="https://doi.org/10.1002/1098-1004(2001)17:1<34::AID-HUMU4>3.0.CO;2-O" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11139240">Zwaenepoel et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11139240" 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="#24" class="mim-tip-reference" title="Zwaenepoel, I., Verpy, E., Blanchard, S., Meins, M., Apfelstedt-Sylla, E., Gal, A., Petit, C. <strong>Identification of three novel mutations in the USH1C gene and detection of thirty-one polymorphisms used for haplotype analysis.</strong> Hum. Mutat. 17: 34-41, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11139240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11139240</a>] [<a href="https://doi.org/10.1002/1098-1004(2001)17:1<34::AID-HUMU4>3.0.CO;2-O" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11139240">Zwaenepoel et al. (2001)</a> found that 2 carriers of the IVS1+1G-T mutation share a common haplotype. A different common haplotype was found in all carriers of the 238_239insC mutation. <a href="#24" class="mim-tip-reference" title="Zwaenepoel, I., Verpy, E., Blanchard, S., Meins, M., Apfelstedt-Sylla, E., Gal, A., Petit, C. <strong>Identification of three novel mutations in the USH1C gene and detection of thirty-one polymorphisms used for haplotype analysis.</strong> Hum. Mutat. 17: 34-41, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11139240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11139240</a>] [<a href="https://doi.org/10.1002/1098-1004(2001)17:1<34::AID-HUMU4>3.0.CO;2-O" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11139240">Zwaenepoel et al. (2001)</a> proposed a founder effect of these 2 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11139240" 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> rs138138689 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs138138689;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/rs138138689?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=rs138138689" 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=rs138138689" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>A complete USH1C mutation screen in 4 carriers of the 238_239insC mutation (<a href="#0002">605242.0002</a>) resulted in the detection of the second mutation in all of the carriers, and the identification of 3 novel mutations of which 2 were splice site mutations (IVS5+1G-A; and IVS1+1G-T, <a href="#0005">605242.0005</a>) and the other a nonsense mutation (R31X; <a href="#0007">605242.0007</a>) (<a href="#24" class="mim-tip-reference" title="Zwaenepoel, I., Verpy, E., Blanchard, S., Meins, M., Apfelstedt-Sylla, E., Gal, A., Petit, C. <strong>Identification of three novel mutations in the USH1C gene and detection of thirty-one polymorphisms used for haplotype analysis.</strong> Hum. Mutat. 17: 34-41, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11139240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11139240</a>] [<a href="https://doi.org/10.1002/1098-1004(2001)17:1<34::AID-HUMU4>3.0.CO;2-O" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11139240">Zwaenepoel et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11139240" 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 an extensive genetic study of 9 Usher syndrome genes in 172 patients with Usher syndrome due to various genetic defects, <a href="#10" class="mim-tip-reference" title="Le Quesne Stabej, P., Saihan, Z., Rangesh, N., Steele-Stallard, H. B., Ambrose, J., Coffey, A., Emmerson, J., Haralambous, E., Hughes, Y., Steel, K. P., Luxon, L. M., Webster, A. R., Bitner-Glindzicz, M. <strong>Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study.</strong> J. Med. Genet. 49: 27-36, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22135276/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22135276</a>] [<a href="https://doi.org/10.1136/jmedgenet-2011-100468" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22135276">Le Quesne Stabej et al. (2012)</a> found that mutations in the USH1C gene were the second most common defect, accounting for 14.9% of families. Four families carried the intron 5 splice site mutation (495+1G-A), and haplotype analysis indicated a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22135276" 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> rs121908370 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908370;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/rs121908370?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=rs121908370" 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=rs121908370" 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=RCV000005453 OR RCV000595941 OR RCV000763238 OR RCV000983994" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005453, RCV000595941, RCV000763238, RCV000983994" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005453...</a>
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<p>A complete USH1C mutation screen in 4 carriers of the 238_239insC mutation (<a href="#0002">605242.0002</a>) resulted in the detection of the second mutation in all of the carriers, and the identification of 3 novel mutations: arg31-to-arg (R31X) and 2 splice site mutations (IVS5+1G-A, <a href="#0006">605242.0006</a>; and IVS1+1G-T, <a href="#0005">605242.0005</a>) (<a href="#24" class="mim-tip-reference" title="Zwaenepoel, I., Verpy, E., Blanchard, S., Meins, M., Apfelstedt-Sylla, E., Gal, A., Petit, C. <strong>Identification of three novel mutations in the USH1C gene and detection of thirty-one polymorphisms used for haplotype analysis.</strong> Hum. Mutat. 17: 34-41, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11139240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11139240</a>] [<a href="https://doi.org/10.1002/1098-1004(2001)17:1<34::AID-HUMU4>3.0.CO;2-O" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11139240">Zwaenepoel et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11139240" 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">rs1592002789 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1592002789;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=rs1592002789" 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=rs1592002789" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In an Indian family in which nonsyndromic recessive deafness (DFNB18A; <a href="/entry/602092">602092</a>) had been mapped to the same region of 11p as USH1C, <a href="#2" class="mim-tip-reference" title="Ahmed, Z. M., Smith, T. N., Riazuddin, S., Makishima, T., Ghosh, M., Bokhari, S., Menon, P. S. N., Deshmukh, D., Griffith, A. J., Riazuddin, S., Friedman, T. B., Wilcox, E. R. <strong>Nonsyndromic recessive deafness DFNB18 and Usher syndrome type IC are allelic mutations of USHIC.</strong> Hum. Genet. 110: 527-531, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12107438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12107438</a>] [<a href="https://doi.org/10.1007/s00439-002-0732-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12107438">Ahmed et al. (2002)</a> identified a leaky splice site mutation in the harmonin gene, a G-to-C transversion at the +5 position of intron 12. Although affected individuals were homozygous for the mutation, wildtype spliced mRNA having exons 11 and 12 as well as mRNA that skipped exon 12 were found. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12107438" 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> rs41282932 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs41282932;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/rs41282932?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=rs41282932" 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=rs41282932" 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=RCV000005455 OR RCV000041259 OR RCV000755427 OR RCV001276292 OR RCV001797045 OR RCV004814837 OR RCV004814838" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005455, RCV000041259, RCV000755427, RCV001276292, RCV001797045, RCV004814837, RCV004814838" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005455...</a>
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<p>In 1 of 32 Chinese multiplex families with nonsyndromic recessive deafness without retinitis pigmentosa (DFNB18A; <a href="/entry/602092">602092</a>), <a href="#13" class="mim-tip-reference" title="Ouyang, X. M., Xia, X. J., Verpy, E., Du, L. L., Pandya, A., Petit, C., Balkany, T., Nance, W. E., Liu, X. Z. <strong>Mutations in the alternatively spliced exons of USH1C cause non-syndromic recessive deafness.</strong> Hum. Genet. 111: 26-30, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12136232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12136232</a>] [<a href="https://doi.org/10.1007/s00439-002-0736-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12136232">Ouyang et al. (2002)</a> found a C-to-G transversion in the alternatively spliced exon D of the USH1C gene, predicting an arg608-to-pro (R608P) substitution in the proline-, serine-, and threonine-rich region of harmonin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12136232" 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> rs55843567 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs55843567;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/rs55843567?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=rs55843567" 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=rs55843567" 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=RCV000005456 OR RCV000041291 OR RCV000972120 OR RCV002496267" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005456, RCV000041291, RCV000972120, RCV002496267" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005456...</a>
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<p>This variant, formerly titled USHER SYNDROME, TYPE IC, has been reclassified based on the findings of <a href="#20" class="mim-tip-reference" title="Shearer, A. E., Eppsteiner, R. W., Booth, K. T., Ephraim, S. S., Gurrola, J., II, Simpson, A., Black-Ziegelbein, E. A., Joshi, S., Ravi, H., Giuffre, A. C., Happe, S., Hildebrand, M. S., and 20 others. <strong>Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants.</strong> Am. J. Hum. Genet. 95: 445-453, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25262649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25262649</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25262649[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.2014.09.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25262649">Shearer et al. (2014)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25262649" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a U.K. patient with type I Usher syndrome (USH1C; <a href="/entry/276904">276904</a>), <a href="#5" class="mim-tip-reference" title="Blaydon, D. C., Mueller, R. F., Hutchin, T. P., Leroy, B. P., Bhattacharya, S. S., Bird, A. C., Malcolm, S., Bitner-Glindzicz, M. <strong>The contribution of USH1C mutations to syndromic and non-syndromic deafness in the UK.</strong> Clin. Genet. 63: 303-307, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12702164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12702164</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2003.00058.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12702164">Blaydon et al. (2003)</a> identified a 388G-A transition in exon 5 of the USH1C gene, resulting in a val130-to-ile (V130I) mutation in the first PDZ domain of the protein. No mutation was identified on the other allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12702164" 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>Based on allele frequency in 8,595 controls from 12 populations (maximum minor allele frequency = 0.0600), <a href="#20" class="mim-tip-reference" title="Shearer, A. E., Eppsteiner, R. W., Booth, K. T., Ephraim, S. S., Gurrola, J., II, Simpson, A., Black-Ziegelbein, E. A., Joshi, S., Ravi, H., Giuffre, A. C., Happe, S., Hildebrand, M. S., and 20 others. <strong>Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants.</strong> Am. J. Hum. Genet. 95: 445-453, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25262649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25262649</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25262649[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.2014.09.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25262649">Shearer et al. (2014)</a> recategorized the V130I variant in the USH1C gene as benign. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25262649" 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> rs397514500 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514500;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/rs397514500?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=rs397514500" 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=rs397514500" 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=RCV000032622 OR RCV000662094 OR RCV000662095 OR RCV000675046 OR RCV001377937" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032622, RCV000662094, RCV000662095, RCV000675046, RCV001377937" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032622...</a>
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<p>In a 42-year-old woman and her 40-year-old brother from a Caucasian British family with hearing loss diagnosed at 4 years of age and retinitis pigmentosa of the 'sector' type (USH1C; <a href="/entry/276904">276904</a>), <a href="#16" class="mim-tip-reference" title="Saihan, Z., Stabej, P. L. Q., Robson, A. G., Rangesh, N., Holder, G. E., Moore, A. T., Steel, K. P., Luxon, L. M., Bitner-Glindzicz, M., Webster, A. R. <strong>Mutations in the USH1C gene associated with sector retinitis pigmentosa and hearing loss.</strong> Retina 31: 1708-1716, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21487335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21487335</a>] [<a href="https://doi.org/10.1097/IAE.0b013e31820d3fd1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21487335">Saihan et al. (2011)</a> identified compound heterozygosity for mutations in the USH1C gene: a 308G-A transition, resulting in an arg103-to-his (R103H) substitution, and a splice site mutation (IVS16-1G-T; 2227-1G-T; <a href="#0012">605242.0012</a>) predicted to abolish the invariant AG dinucleotide splice acceptor site and create a new acceptor site 10 nucleotides downstream that would result in skipping of exon 22 and an in-frame loss of 18 amino acids. The sibs' unaffected parents were each heterozygous for 1 of the mutations, neither of which was found in 866 control chromosomes. <a href="#16" class="mim-tip-reference" title="Saihan, Z., Stabej, P. L. Q., Robson, A. G., Rangesh, N., Holder, G. E., Moore, A. T., Steel, K. P., Luxon, L. M., Bitner-Glindzicz, M., Webster, A. R. <strong>Mutations in the USH1C gene associated with sector retinitis pigmentosa and hearing loss.</strong> Retina 31: 1708-1716, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21487335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21487335</a>] [<a href="https://doi.org/10.1097/IAE.0b013e31820d3fd1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21487335">Saihan et al. (2011)</a> noted that the R103H mutation had previously been reported: it was identified in compound heterozygosity with a different splice site mutation in a French USH1 patient, and was not found in a panel of 352 chromosomes in that study (<a href="#15" class="mim-tip-reference" title="Roux, A.-F., Faugere, V., Le Guedard, S., Pallares-Ruiz, N., Vielle, A., Chambert, S., Marlin, S., Hamel, C., Gilbert, B., Malcolm, S., Claustres, M. <strong>Survey of the frequency of USH1 gene mutations in a cohort of Usher patients shows the importance of cadherin 23 and protocadherin 15 genes and establishes a detection rate of above 90%.</strong> J. Med. Genet. 43: 763-768, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16679490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16679490</a>] [<a href="https://doi.org/10.1136/jmg.2006.041954" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16679490">Roux et al., 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16679490+21487335" 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>For discussion of the splice site mutation (IVS16-1G-T) in the USH1C gene that was found in compound heterozygous state in a 42-year-old woman and her 40-year-old brother with Usher syndrome type IC (USH1C; <a href="/entry/276904">276904</a>) by <a href="#16" class="mim-tip-reference" title="Saihan, Z., Stabej, P. L. Q., Robson, A. G., Rangesh, N., Holder, G. E., Moore, A. T., Steel, K. P., Luxon, L. M., Bitner-Glindzicz, M., Webster, A. R. <strong>Mutations in the USH1C gene associated with sector retinitis pigmentosa and hearing loss.</strong> Retina 31: 1708-1716, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21487335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21487335</a>] [<a href="https://doi.org/10.1097/IAE.0b013e31820d3fd1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21487335">Saihan et al. (2011)</a>, see <a href="#0011">605242.0011</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21487335" 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> rs1207247951 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1207247951;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/rs1207247951?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=rs1207247951" 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=rs1207247951" 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=RCV000670807 OR RCV001003245 OR RCV001386148 OR RCV001829866 OR RCV004568539" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000670807, RCV001003245, RCV001386148, RCV001829866, RCV004568539" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000670807...</a>
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<p>In 12 patients from 8 Israeli families of Yemenite Jewish origin with retinitis pigmentosa and late-onset hearing loss (USH1C; <a href="/entry/276904">276904</a>), <a href="#9" class="mim-tip-reference" title="Khateb, S., Zelinger, L., Ben-Yosef, T., Merin, S., Crystal-Shalit, O., Gross, M., Banin, E., Sharon, D. <strong>Exome sequencing identifies a founder frameshift mutation in an alternative exon of USH1C as the cause of autosomal recessive retinitis pigmentosa with late-onset hearing loss.</strong> PLoS One 7: e51566, 2012. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23251578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23251578</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23251578[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/10.1371/journal.pone.0051566" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23251578">Khateb et al. (2012)</a> identified homozygosity for a 1-bp deletion (1220delG) in alternative exon 15 of the USH1C gene, predicted to cause a frameshift (Gly407GlufsTer56). Extensive RT-PCR analysis revealed that the novel splice variant includes all USH1C coding exons and is ubiquitously expressed at relatively low levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23251578" 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>Interactions in the network of Usher syndrome type 1 proteins.</strong>
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Hum. Molec. Genet. 14: 347-356, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15590703/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15590703</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15590703" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<p class="mim-text-font">
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[<a href="https://doi.org/10.1007/s00439-002-0732-4" target="_blank">Full Text</a>]
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</p>
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[<a href="https://doi.org/10.1093/hmg/ddq271" target="_blank">Full Text</a>]
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<strong>A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C gene.</strong>
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[<a href="https://doi.org/10.1038/79178" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1034/j.1399-0004.2003.00058.x" target="_blank">Full Text</a>]
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<strong>Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12485990/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12485990</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12485990[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=12485990" 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/emboj/cdf689" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/humu.20133" target="_blank">Full Text</a>]
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<strong>Mouse models of USH1C and DFNB18: phenotypic and molecular analyses of two new spontaneous mutations of the Ush1c gene.</strong>
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[<a href="https://doi.org/10.1093/hmg/ddg332" target="_blank">Full Text</a>]
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<strong>Exome sequencing identifies a founder frameshift mutation in an alternative exon of USH1C as the cause of autosomal recessive retinitis pigmentosa with late-onset hearing loss.</strong>
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[<a href="https://doi.org/10.1371/journal.pone.0051566" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmedgenet-2011-100468" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/79186" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1046/j.0009-9163.2002.00004.x" target="_blank">Full Text</a>]
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<strong>Mutations in the alternatively spliced exons of USH1C cause non-syndromic recessive deafness.</strong>
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[<a href="https://doi.org/10.1007/s00439-002-0736-0" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16301216/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16301216</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16301216" 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/ddi417" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.2006.041954" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9760205/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9760205</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9760205" 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/s004390050806" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="18" class="mim-anchor"></a>
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<a id="Savas2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Savas, S., Frischhertz, B., Pelias, M. Z., Batzer, M. A., Deininger, P. L., Keats, B. J. B.
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|
<strong>The USH1C 216G-A mutation and the 9-repeat VNTR(t,t) allele are in complete linkage disequilibrium in the Acadian population.</strong>
|
|
Hum. Genet. 110: 95-97, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11810303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11810303</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11810303" 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/s00439-001-0653-7" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="19" class="mim-anchor"></a>
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<a id="Scanlan1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Scanlan, M. J., Williamson, B., Jungbluth, A., Stockert, E., Arden, K. C., Viars, C. S., Gure, A. O., Gordan, J. D., Chen, Y.-T., Old, L. J.
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|
<strong>Isoforms of the human PDZ-73 protein exhibit differential tissue expression.</strong>
|
|
Biochim. Biophys. Acta 1445: 39-52, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10209257/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10209257</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10209257" 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/s0167-4781(99)00033-0" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="20" class="mim-anchor"></a>
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<a id="Shearer2014" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Shearer, A. E., Eppsteiner, R. W., Booth, K. T., Ephraim, S. S., Gurrola, J., II, Simpson, A., Black-Ziegelbein, E. A., Joshi, S., Ravi, H., Giuffre, A. C., Happe, S., Hildebrand, M. S., and 20 others.
|
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<strong>Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants.</strong>
|
|
Am. J. Hum. Genet. 95: 445-453, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25262649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25262649</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25262649[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=25262649" 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.2014.09.001" target="_blank">Full Text</a>]
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<a id="21" class="mim-anchor"></a>
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<a id="Siemens2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Siemens, J., Kazmierczak, P., Reynolds, A., Sticker, M., Littlewood-Evans, A., Muller, U.
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<strong>The Usher syndrome proteins cadherin 23 and harmonin form a complex by means of PDZ-domain interactions.</strong>
|
|
Proc. Nat. Acad. Sci. 99: 14946-14951, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12407180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12407180</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12407180[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=12407180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.232579599" target="_blank">Full Text</a>]
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<li>
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<a id="22" class="mim-anchor"></a>
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<a id="Turner2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Turner, C., Killoran, C., Thomas, N. S. T., Rosenberg, M., Chuzhanova, N. A., Johnston, J., Kemel, Y., Cooper, D. N., Biesecker, L. G.
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<strong>Human genetic disease caused by de novo mitochondrial-nuclear DNA transfer.</strong>
|
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Hum. Genet. 112: 303-309, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12545275/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12545275</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12545275" 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/s00439-002-0892-2" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="23" class="mim-anchor"></a>
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<a id="Verpy2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Verpy, E., Leibovici, M., Zwaenepoel, I., Liu, X.-Z., Gal, A., Salem, N., Mansour, A., Blanchard, S., Kobayashi, I., Keats, B. J. B., Slim, R., Petit, C.
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<strong>A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C.</strong>
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Nature Genet. 26: 51-55, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973247</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10973247" 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/10.1038/79171" target="_blank">Full Text</a>]
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<li>
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<a id="24" class="mim-anchor"></a>
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<a id="Zwaenepoel2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zwaenepoel, I., Verpy, E., Blanchard, S., Meins, M., Apfelstedt-Sylla, E., Gal, A., Petit, C.
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<strong>Identification of three novel mutations in the USH1C gene and detection of thirty-one polymorphisms used for haplotype analysis.</strong>
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Hum. Mutat. 17: 34-41, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11139240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11139240</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11139240" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/1098-1004(2001)17:1<34::AID-HUMU4>3.0.CO;2-O" target="_blank">Full Text</a>]
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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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<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>
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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 : 10/28/2014
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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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Marla J. F. O'Neill - updated : 1/16/2013<br>Patricia A. Hartz - updated : 5/2/2012<br>Cassandra L. Kniffin - updated : 4/25/2012<br>George E. Tiller - updated : 7/6/2009<br>George E. Tiller - updated : 12/12/2007<br>George E. Tiller - updated : 1/11/2006<br>Victor A. McKusick - updated : 3/7/2005<br>Victor A. McKusick - updated : 5/12/2003<br>Victor A. McKusick - updated : 4/22/2003<br>Patricia A. Hartz - updated : 3/10/2003<br>Victor A. McKusick - updated : 12/6/2002<br>Victor A. McKusick - updated : 9/9/2002<br>Victor A. McKusick - updated : 8/13/2002<br>Victor A. McKusick - updated : 1/25/2002<br>Victor A. McKusick - updated : 1/25/2001
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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">
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Victor A. McKusick : 8/29/2000
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</span>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<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">
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carol : 02/06/2020
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 02/05/2020<br>carol : 11/26/2019<br>carol : 11/25/2019<br>carol : 07/22/2015<br>alopez : 10/28/2014<br>joanna : 2/26/2014<br>tpirozzi : 7/1/2013<br>carol : 1/23/2013<br>terry : 1/16/2013<br>alopez : 12/13/2012<br>carol : 11/27/2012<br>mgross : 5/2/2012<br>mgross : 5/2/2012<br>carol : 4/26/2012<br>ckniffin : 4/25/2012<br>alopez : 7/20/2009<br>alopez : 7/10/2009<br>terry : 7/6/2009<br>terry : 12/12/2008<br>wwang : 12/28/2007<br>terry : 12/12/2007<br>wwang : 1/24/2006<br>terry : 1/11/2006<br>wwang : 5/27/2005<br>tkritzer : 3/14/2005<br>terry : 3/7/2005<br>tkritzer : 5/14/2003<br>terry : 5/12/2003<br>tkritzer : 4/29/2003<br>terry : 4/22/2003<br>carol : 4/18/2003<br>mgross : 3/13/2003<br>mgross : 3/13/2003<br>terry : 3/10/2003<br>carol : 12/10/2002<br>tkritzer : 12/6/2002<br>alopez : 9/9/2002<br>tkritzer : 8/19/2002<br>tkritzer : 8/15/2002<br>terry : 8/13/2002<br>carol : 2/7/2002<br>carol : 2/7/2002<br>mcapotos : 2/6/2002<br>terry : 1/25/2002<br>carol : 12/5/2001<br>carol : 12/5/2001<br>carol : 10/23/2001<br>cwells : 1/29/2001<br>carol : 1/29/2001<br>cwells : 1/29/2001<br>terry : 1/25/2001<br>terry : 10/11/2000<br>alopez : 9/12/2000<br>alopez : 8/29/2000
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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 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>
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<span class="mim-font">
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<strong>*</strong> 605242
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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USH1 PROTEIN NETWORK COMPONENT HARMONIN; USH1C
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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>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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USH1C GENE<br />
|
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HARMONIN<br />
|
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PDZ DOMAIN-CONTAINING PROTEIN, 73-KD; PDZ73
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: USH1C</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">
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<strong>
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<em>
|
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Cytogenetic location: 11p15.1
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|
Genomic coordinates <span class="small">(GRCh38)</span> : 11:17,493,900-17,544,416 </span>
|
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</em>
|
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</strong>
|
|
<span class="small">(from NCBI)</span>
|
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</span>
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</p>
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</div>
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<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-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
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<tr class="active">
|
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<th>
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|
Location
|
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</th>
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<th>
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|
Phenotype
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</th>
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<th>
|
|
Phenotype <br /> MIM number
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</th>
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<th>
|
|
Inheritance
|
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</th>
|
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<th>
|
|
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="2">
|
|
<span class="mim-font">
|
|
11p15.1
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Deafness, autosomal recessive 18A
|
|
</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
602092
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
Autosomal recessive
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
3
|
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</span>
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</td>
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</tr>
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<tr>
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<td>
|
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<span class="mim-font">
|
|
Usher syndrome, type 1C
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
276904
|
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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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Autosomal recessive
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<td>
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<span class="mim-font">
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3
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</tbody>
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</table>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>By serologic expression cloning, Scanlan et al. (1999) cloned USH1C, which they designated PDZ73, from a metastatic colon cancer cDNA expression library. The deduced full-length 652-amino acid protein has a calculated molecular mass of about 73 kD. It contains an N-terminal domain followed by 2 PDZ domains; a coiled-coil region with a bipartite nuclear localization signal; a PEST degradation sequence; a third PDZ domain; and a C-terminal domain. PDZ73 also has an N-glycosylation site and 17 putative phosphorylation sites. Scanlan et al. (1999) identified several splice variants. One variant encodes a deduced 403-amino acid protein with a calculated molecular mass of about 45 kD. This variant lacks the C-terminal half of the full-length protein, including the PEST sequence, the third PDZ domain, and the C-terminal region. Another variant, which predominates in brain, encodes a putative 328-amino acid protein with a calculated molecular mass of about 37 kD. This variant lacks the N-terminal half of the full-length protein and begins with part of the coiled-coil domain. Northern blot analysis revealed expression of a major 2.4-kb transcript in small intestine, colon, pancreas, kidney, and liver, with lower levels in testis. Although the 2.4-kb transcript was expressed in whole brain, a 1.3-kb transcript, which encodes the 37-kD protein, predominated. Northern blot analysis of specific brain regions detected expression of the 1.3-kb transcript specifically in spinal cord and medulla. RT-PCR detected expression of the transcript corresponding to the 73-kD protein in 13 of 20 samples tested. Expression of the transcript corresponding to the 45-kD protein was detected only in colon, small intestine, testis, brain, and kidney. Other variants showed more restricted expression. Immunohistochemical localization of PDZ73 revealed expression in epithelial cells, specifically at the apical cell border of the small intestine, in proximal and distal cortical tubules of the kidney, and in the cytoplasm of colonic epithelium. Scanlan et al. (1999) believed that the protein stained in these sections represents the 45-kD isoform. </p><p>Usher syndrome type I is an autosomal recessive sensory defect involving congenital profound sensorineural deafness, vestibular dysfunction, and blindness due to progressive retinitis pigmentosa. Usher syndrome type IC (USH1C; 276904) is a subtype mapping to 11p14.3 that had been described in a population of Louisiana Acadians and in a Lebanese family. By studying a subtracted mouse cDNA library derived from inner ear sensory areas, Verpy et al. (2000) demonstrated that the gene responsible for Usher syndrome type IC encodes a PDZ domain-containing protein. They named the protein encoded by the USH1C gene 'harmonin,' from the Greek word 'harmonia,' meaning 'assembling.' They showed that, in the mouse inner ear, only the sensory hair cells express harmonin. The inner ear Ush1c transcripts predicted several harmonin isoforms, some containing an additional coiled-coil domain and a proline- and serine-rich region. Several of these transcripts were absent from the eye. </p><p>Montell (2000) reviewed the information on the USH1C gene provided by the report of Verpy et al. (2000) and Bitner-Glindzicz et al. (2000). The organization of signaling and cytoskeletal proteins in complexes is coordinated by scaffold proteins composed of multiple protein interaction domains. One such module is the PDZ domain, so-called for the first 3 proteins known to contain it: PSD95 (602887), DLG (see 604090), and ZO1 (601009). </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>By genomic sequence analysis and FISH, Scanlan et al. (1999) mapped the PDZ73 gene to chromosome 11p15.4-p15.1. </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>Siemens et al. (2002) showed that harmonin and CDH23 (605516), another protein that is the site of mutations causing Usher syndrome, form a protein complex. Two PDZ domains in harmonin interact with 2 complementary binding surfaces in the CDH23 cytoplasmic domain. One of the binding surfaces is disrupted by sequences encoded by an alternatively spliced CDH23 exon that is expressed in the ear, but not in the retina. In the ear, CDH23 and harmonin are expressed in the stereocilia of hair cells, and in the retina within the photoreceptor cell layer. Because Cdh23-deficient mice have splayed stereocilia, Siemens et al. (2002) suggested that CDH23 and harmonin are part of a transmembrane complex that connects stereocilia into a bundle, and that defects in the formation of this complex may disrupt stereocilia bundles and cause deafness in patients with Usher syndrome type I. </p><p>Boeda et al. (2002) noted that defects in the MYO7A (276903), CDH23, and harmonin genes result in forms of Usher syndrome. They observed severely disorganized hair bundles in shaker-1 mice, which carry a mutation in the Myo7a gene. Immunohistochemical analysis of differentiating hair cells indicated that Cdh23 was distributed normally, but harmonin b was not. Using human and mouse cDNA constructs and cells, they confirmed interaction between harmonin and CDH23 in vitro and in vivo. They also provided evidence that harmonin b anchors CDH23 to the stereocilia microfilaments and interacts directly with MYO7A, which conveys harmonin b along the actin core of the developing stereocilia. Boeda et al. (2002) proposed that the shaping of the hair bundle relies on a functional unit composed of MYO7A, harmonin b, and CDH23, and that the interaction of these proteins ensures the cohesion of the stereocilia. </p><p>By using cotransfection and immunolocalization techniques, Adato et al. (2005) documented the interaction between SANS (USH1G; 607696) and harmonin, and also determined that SANS binds to myosin VIIa. The authors noted that harmonin b could interact with all harmonin isoforms and that harmonin bound to protocadherin-15 (PCDH15; 605514). Adato et al. (2005) proposed that, via its binding to myosin VIIa and/or harmonin, SANS controls the hair bundle cohesion and proper development by regulating the traffic of USH1 proteins en route to the stereocilia. </p><p>Reiners et al. (2005) demonstrated a molecular interaction between the scaffold protein harmonin, the USH2A protein usherin (608400), VLGR1 (USH2C; 602851), and NBC3 (SLC4A7; 603353). The authors pinpointed these interactions to the PDZ1 domain of harmonin and the PDZ-binding motifs at the C termini of the USH2 proteins and NBC3. USH2A, VLGR1, and NBC3 are coexpressed with the USH1 protein harmonin in the synaptic terminals of both retinal photoreceptors and inner ear hair cells. In hair cells, these USH proteins are also localized in the signal uptaking stereocilia. The authors concluded that the USH2 proteins and NBC3 are partners in the supramolecular USH protein network in the retina and inner ear. </p><p>Bahloul et al. (2010) found that both isoforms of mouse Cdh23 bound directly to the harmonin A isoform and to the tail of myosin-7a. The 3 proteins formed a complex that interacted with phosphatidylinositol 4,5-bisphosphate in synthetic liposomes. Knockout of Cdh23 in mice resulted in loss of harmonin from the apex of hair bundles in the organ of Corti and caused redistribution of a weakened myosin-7a signal along stereocilia. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In patients with Usher syndrome type IC, Verpy et al. (2000) found a splice site mutation (605242.0001), a frameshift mutation (605242.0002), and the expansion of an intronic variable number of tandem repeats (VNTRs) (605242.0003) in the USH1C gene. Verpy et al. (2000) proposed that mutation in the USH1C gene also underlies the form of nonsyndromic autosomal recessive neurosensory deafness designated DFNB18 (DFNB18A; 602092), which maps to the same region of 11p. Ouyang et al. (2002) indeed found a family with profound deafness without retinitis pigmentosa due to a mutation in the USH1C gene (605242.0009). Ahmed et al. (2002) identified a splice site mutation in intron 12 of the harmonin gene (605242.0008) in a family with DFNB18A. </p><p>Bitner-Glindzicz et al. (2000) identified a partial deletion of the USH1C gene in a contiguous gene deletion syndrome (606528). </p><p>Ouyang et al. (2003) determined the frequency of USH1C mutations as a cause of Usher syndrome type I by studying 128 probands, 7 from Acadian and 121 from non-Acadian populations. All 7 Acadian Usher syndrome type I patients were found to be homozygous for both the 216G-A mutation (605242.0004) and the 9-repeat VNTR (605242.0003), which the authors referred to as the Acadian alleles, confirming previous evidence for a founder effect by haplotype analysis. However, USH1C mutations were identified in only 2 of the non-Acadian probands (1.65%): 1 from Pakistan who was homozygous for a 1-bp insertion (238_239insC; 605242.0002) and 1 from Canada who was homozygous for the Acadian alleles. The affected haplotypes in the Canadian patient in comparison with the Acadian patients yielded evidence for a founder effect. Ouyang et al. (2003) suggested that Usher syndrome type IC is a relatively rare form of Usher syndrome type I in non-Acadian populations, and that the high frequency of the 238_239insC mutation in the study of Zwaenepoel et al. (2001) in Germany may reflect a founder effect. </p><p>In the U.K., Blaydon et al. (2003) found no mutations in the USH1C gene in patients with nonsyndromic deafness but found more instances of USH1C mutations in Usher syndrome type I than had previously been thought to occur. The 238_239insC mutation (605242.0002) was found in homozygous state in an Usher syndrome type I patient of Greek Cypriot origin. </p><p>In a metaanalysis of gross insertions causing human genetic disease based on sequence data in the Human Gene Mutation Database, Chen et al. (2005) found an example of a 36-bp insertion in exon 9 of the USH1C gene, the origin of which was the mitochondrial chromosome. Turner et al. (2003) reported a 72-bp insertion of mitochondrial DNA in the GLI3 gene (165240). </p><p>In 2 sibs from a Caucasian British family with hearing loss diagnosed at 4 years of age and retinitis pigmentosa of the 'sector' type, who were negative for pathogenic changes in 7 other Usher-associated genes, Saihan et al. (2011) identified compound heterozygosity for a missense mutation (R103H; 605242.0011) and a splice site mutation (605242.0012) in the USH1C gene. </p><p>In 12 patients from 8 Israeli families of Yemenite Jewish origin with retinitis pigmentosa and late-onset hearing loss, Khateb et al. (2012) identified homozygosity for a 1-bp deletion in the USH1C gene (1220delG; 605242.0013). A carrier frequency of 0.008 for the 1220G mutation was found in the Israeli Yemenite Jewish population. </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>Johnson et al. (2003) mapped 2 recessive, allelic murine mutations causing circling behavior and deafness to the same region on chromosome 7. The 'deaf circler' (dfcr) mutation is a 12.8-kb intragenic deletion in Ush1c that eliminates 3 constitutive and 5 alternatively spliced exons. The 'deaf circler-2 Jackson' (dfcr-2J) mutation is a 1-bp deletion in an alternatively spliced exon of Ush1c that creates a transcriptional frameshift, changing 38 amino acid codons before introducing a premature stop codon. Both mutations cause congenital deafness and severe balance deficits due to inner ear dysfunction. The stereocilia of cochlear hair cells are disorganized and splayed in mutant mice, with subsequent degeneration of the hair cells and spiral ganglion cells. Harmonin had been shown to bind, by means of its PDZ-domains, with the products of other Usher syndrome genes, including Myo7a, Cdh23, and Sans. The complexes formed by these protein interactions are thought to be essential for maintaining the integrity of hair cell stereocilia. </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>13 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 IC</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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USH1C, IVS5AS, A DEL, -2
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<br />
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SNP: rs1480243085,
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gnomAD: rs1480243085,
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ClinVar: RCV000005447, RCV001003246, RCV001383896, RCV003466820, RCV004814836, RCV005041990
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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 patients with Usher syndrome type IC (276904) in a consanguineous Lebanese family (Saouda et al., 1998), Verpy et al. (2000) identified deletion of 1 nucleotide at the intron 5/exon 6 junction of the USH1C gene. This mutation (IVS5-2delA) affected the invariant A of the acceptor splice site AG dinucleotide and was therefore expected to lead to aberrant splicing, such as a skipping of the 25-bp exon 6, creating a premature stop codon in exon 8. The same mutation was found in homozygous state in 8 Usher syndrome type I affected children from an unrelated Lebanese family. </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 IC</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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USH1C, 1-BP INS, 238C
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<br />
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SNP: rs397515359,
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gnomAD: rs397515359,
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ClinVar: RCV000005448, RCV000213574, RCV000505081, RCV000727619, RCV000787893, RCV000824775, RCV000984011, RCV001073457, RCV001291493, RCV004755713, RCV005003337
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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 Muslim family living in England with Usher syndrome type IC (276904) with 3 affected children, Verpy et al. (2000) found insertion of a C within a stretch of 6 consecutive cytosines (nucleotide positions 233-238) in exon 3 of the USH1C gene. This insertion (238_239insC) was expected to result in translation of 68 out-of-frame amino acids and protein termination at codon 148 in exon 5. Verpy et al. (2000) found the same 238_239insC mutation in 4 patients from Germany (all of European descent) with Usher syndrome but no detected mutations of MYO7A (276903). Bitner-Glindzicz et al. (2000) likewise found this insertion in a Pakistani family. </p><p>Zwaenepoel et al. (2001) found that all carriers of the 238_239insC mutation share a common haplotype. A different common haplotype was found in 2 carriers of the IVS1+1G-T mutation (605242.0005). Zwaenepoel et al. (2001) proposed a founder effect of these 2 mutations. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 USHER SYNDROME, TYPE IC</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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USH1C, VNTR EXP
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<br />
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SNP: rs55983148,
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ClinVar: RCV000005449, RCV000218261
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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 Louisiana-Acadian patients with Usher syndrome type IC (276904), Verpy et al. (2000) found no mutation in the coding sequence of the harmonin gene; however, they detected an expansion of a variable number of tandem repeats (VNTR) of a 45-bp element in intron 5 of the USH1C gene. They detected no control individuals with 2 alleles bearing more than 6 repeats. In all but 1 of 11 Acadian patients, they found an allele with 9 tandem repeats in the homozygous state. These 10 individuals were from 7 families. The remaining Acadian patient carried the 9 tandem repeats on 1 chromosome and the 238_239insC mutation (605242.0002) on the other. Verpy et al. (2000) proposed that this 405-bp intronic sequence composed of 9 tandem repeats was responsible for the disease in the Acadian population of Louisiana. The repeat expansion was predicted to inhibit transcription, as shown for the expanded GAA triplet repeats from intron 1 of the Friedreich ataxia gene (229300). Alternatively, it may cause abnormal posttranscriptional processing. </p><p>Savas et al. (2002) found that 43 of 44 Acadian patients with Usher syndrome were homozygous for both a 216G-A mutation (605242.0004) and the 45-bp VNTR polymorphism in the USH1C gene. The remaining Acadian patient was a compound heterozygote for the 216G-A allele (with the intron 5 VNTR in cis) and 238_239insC (605242.0002), an USH1C mutation found in other populations. The findings demonstrated that the VNTR polymorphism, designated 9VNTR(t,t), had complete linkage disequilibrium with the 216G-A mutation in the Acadian 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 IC</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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USH1C, 216G-A
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<br />
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SNP: rs151045328,
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gnomAD: rs151045328,
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ClinVar: RCV000005450, RCV000220605, RCV000504855, RCV000724016, RCV000763237, RCV000824776, RCV000984012, RCV004755714
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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 cell lines from an Acadian family with Usher syndrome type IC (276904), Bitner-Glindzicz et al. (2000) found a G-to-A change at position 216 of the USH1C cDNA. The affected individual was homozygous for the substitution and the parents were heterozygous. Although this substitution did not change an amino acid, examination of the sequence suggested that it might create a new splice site. Analysis of USH1C lymphoblastoid cDNA from the Acadian family showed that the affected individual produced a shortened RT-PCR product. Sequencing revealed a 39-bp deletion, consistent with the creation of a new splice site within exon 3. </p><p>Savas et al. (2002) found that 43 of 44 Acadian patients with Usher syndrome were homozygous for both the 216G-A mutation and for the 45-bp VNTR polymorphism in intron 5 (605242.0003) of the USH1C gene. The remaining Acadian patient was a compound heterozygote for the 216G-A allele (with the intron 5 VNTR in cis) and 238_239insC (605242.0002), an USH1C mutation found in other populations. The findings demonstrated that the VNTR polymorphism, designated 9VNTR(t,t), had complete linkage disequilibrium with the 216G-A mutation in the Acadian population. Among 82 Acadian controls, 1 was heterozygous for 216G-A/9VNTR(t,t). The 238_239insC mutation was not found in Acadian controls. </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 IC</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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USH1C, IVS1DS, G-T, +1
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<br />
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SNP: rs1403777293,
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gnomAD: rs1403777293,
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ClinVar: RCV000005451
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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>A complete USH1C mutation screen in 4 carriers of the 238_239insC mutation (605242.0002) resulted in the detection of the second mutation in all of the carriers, and the identification of 3 novel mutations of which 2 were splice site mutations (IVS1+1G-T; IVS5+1G-A, 605242.0006) and the other a nonsense mutation (R31X; 605242.0007) (Zwaenepoel et al., 2001). </p><p>Zwaenepoel et al. (2001) found that 2 carriers of the IVS1+1G-T mutation share a common haplotype. A different common haplotype was found in all carriers of the 238_239insC mutation. Zwaenepoel et al. (2001) proposed a founder effect of these 2 mutations. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0006 USHER SYNDROME, TYPE IC</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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USH1C, IVS5DS, G-A, +1
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<br />
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SNP: rs138138689,
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gnomAD: rs138138689,
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ClinVar: RCV000411458, RCV001240003, RCV001266797, RCV003328125, RCV005044619
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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>A complete USH1C mutation screen in 4 carriers of the 238_239insC mutation (605242.0002) resulted in the detection of the second mutation in all of the carriers, and the identification of 3 novel mutations of which 2 were splice site mutations (IVS5+1G-A; and IVS1+1G-T, 605242.0005) and the other a nonsense mutation (R31X; 605242.0007) (Zwaenepoel et al., 2001). </p><p>In an extensive genetic study of 9 Usher syndrome genes in 172 patients with Usher syndrome due to various genetic defects, Le Quesne Stabej et al. (2012) found that mutations in the USH1C gene were the second most common defect, accounting for 14.9% of families. Four families carried the intron 5 splice site mutation (495+1G-A), and haplotype analysis indicated a founder effect. </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 USHER SYNDROME, TYPE IC</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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USH1C, ARG31TER
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<br />
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SNP: rs121908370,
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gnomAD: rs121908370,
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ClinVar: RCV000005453, RCV000595941, RCV000763238, RCV000983994
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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>A complete USH1C mutation screen in 4 carriers of the 238_239insC mutation (605242.0002) resulted in the detection of the second mutation in all of the carriers, and the identification of 3 novel mutations: arg31-to-arg (R31X) and 2 splice site mutations (IVS5+1G-A, 605242.0006; and IVS1+1G-T, 605242.0005) (Zwaenepoel et al., 2001). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0008 DEAFNESS, AUTOSOMAL RECESSIVE 18A</strong>
|
|
</span>
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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USH1C, IVS12DS, G-C, +5
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<br />
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SNP: rs1592002789,
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ClinVar: RCV000005454
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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 an Indian family in which nonsyndromic recessive deafness (DFNB18A; 602092) had been mapped to the same region of 11p as USH1C, Ahmed et al. (2002) identified a leaky splice site mutation in the harmonin gene, a G-to-C transversion at the +5 position of intron 12. Although affected individuals were homozygous for the mutation, wildtype spliced mRNA having exons 11 and 12 as well as mRNA that skipped exon 12 were found. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 DEAFNESS, AUTOSOMAL RECESSIVE 18A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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USH1C, ARG608PRO
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<br />
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SNP: rs41282932,
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gnomAD: rs41282932,
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ClinVar: RCV000005455, RCV000041259, RCV000755427, RCV001276292, RCV001797045, RCV004814837, RCV004814838
|
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|
</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 1 of 32 Chinese multiplex families with nonsyndromic recessive deafness without retinitis pigmentosa (DFNB18A; 602092), Ouyang et al. (2002) found a C-to-G transversion in the alternatively spliced exon D of the USH1C gene, predicting an arg608-to-pro (R608P) substitution in the proline-, serine-, and threonine-rich region of harmonin. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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|
|
USH1C, VAL130ILE
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<br />
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SNP: rs55843567,
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gnomAD: rs55843567,
|
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|
|
ClinVar: RCV000005456, RCV000041291, RCV000972120, RCV002496267
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant, formerly titled USHER SYNDROME, TYPE IC, has been reclassified based on the findings of Shearer et al. (2014). </p><p>In a U.K. patient with type I Usher syndrome (USH1C; 276904), Blaydon et al. (2003) identified a 388G-A transition in exon 5 of the USH1C gene, resulting in a val130-to-ile (V130I) mutation in the first PDZ domain of the protein. No mutation was identified on the other allele. </p><p>Based on allele frequency in 8,595 controls from 12 populations (maximum minor allele frequency = 0.0600), Shearer et al. (2014) recategorized the V130I variant in the USH1C gene as benign. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
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</div>
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<div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 USHER SYNDROME, TYPE IC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
USH1C, ARG103HIS
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<br />
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|
|
SNP: rs397514500,
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|
|
gnomAD: rs397514500,
|
|
|
|
|
|
ClinVar: RCV000032622, RCV000662094, RCV000662095, RCV000675046, RCV001377937
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 42-year-old woman and her 40-year-old brother from a Caucasian British family with hearing loss diagnosed at 4 years of age and retinitis pigmentosa of the 'sector' type (USH1C; 276904), Saihan et al. (2011) identified compound heterozygosity for mutations in the USH1C gene: a 308G-A transition, resulting in an arg103-to-his (R103H) substitution, and a splice site mutation (IVS16-1G-T; 2227-1G-T; 605242.0012) predicted to abolish the invariant AG dinucleotide splice acceptor site and create a new acceptor site 10 nucleotides downstream that would result in skipping of exon 22 and an in-frame loss of 18 amino acids. The sibs' unaffected parents were each heterozygous for 1 of the mutations, neither of which was found in 866 control chromosomes. Saihan et al. (2011) noted that the R103H mutation had previously been reported: it was identified in compound heterozygosity with a different splice site mutation in a French USH1 patient, and was not found in a panel of 352 chromosomes in that study (Roux et al., 2006). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 USHER SYNDROME, TYPE IC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
USH1C, IVS16AS, G-T, -1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs778110397,
|
|
|
|
|
|
gnomAD: rs778110397,
|
|
|
|
|
|
ClinVar: RCV000032623
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the splice site mutation (IVS16-1G-T) in the USH1C gene that was found in compound heterozygous state in a 42-year-old woman and her 40-year-old brother with Usher syndrome type IC (USH1C; 276904) by Saihan et al. (2011), see 605242.0011. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 USHER SYNDROME, TYPE IC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
USH1C, 1-BP DEL, 1220G
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1207247951,
|
|
|
|
|
|
gnomAD: rs1207247951,
|
|
|
|
|
|
ClinVar: RCV000670807, RCV001003245, RCV001386148, RCV001829866, RCV004568539
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 12 patients from 8 Israeli families of Yemenite Jewish origin with retinitis pigmentosa and late-onset hearing loss (USH1C; 276904), Khateb et al. (2012) identified homozygosity for a 1-bp deletion (1220delG) in alternative exon 15 of the USH1C gene, predicted to cause a frameshift (Gly407GlufsTer56). Extensive RT-PCR analysis revealed that the novel splice variant includes all USH1C coding exons and is ubiquitously expressed at relatively low levels. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
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|
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|
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|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Adato, A., Michel, V., Kikkawa, Y., Reiners, J., Alagramam, K. N., Weil, D., Yonekawa, H., Wolfrum, U., El-Amraoui, A., Petit, C.
|
|
<strong>Interactions in the network of Usher syndrome type 1 proteins.</strong>
|
|
Hum. Molec. Genet. 14: 347-356, 2005.
|
|
|
|
|
|
[PubMed: 15590703]
|
|
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|
|
[Full Text: https://doi.org/10.1093/hmg/ddi031]
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|
|
</p>
|
|
</li>
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|
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<li>
|
|
<p class="mim-text-font">
|
|
Ahmed, Z. M., Smith, T. N., Riazuddin, S., Makishima, T., Ghosh, M., Bokhari, S., Menon, P. S. N., Deshmukh, D., Griffith, A. J., Riazuddin, S., Friedman, T. B., Wilcox, E. R.
|
|
<strong>Nonsyndromic recessive deafness DFNB18 and Usher syndrome type IC are allelic mutations of USHIC.</strong>
|
|
Hum. Genet. 110: 527-531, 2002.
|
|
|
|
|
|
[PubMed: 12107438]
|
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|
|
[Full Text: https://doi.org/10.1007/s00439-002-0732-4]
|
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|
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</p>
|
|
</li>
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|
<li>
|
|
<p class="mim-text-font">
|
|
Bahloul, A., Michel, V., Hardelin, J.-P., Nouaille, S., Hoos, S., Houdusse, A., England, P., Petit, C.
|
|
<strong>Cadherin-23, myosin VIIa and harmonin, encoded by Usher syndrome type I genes, for a ternary complex and interact with membrane phospholipids.</strong>
|
|
Hum. Molec. Genet. 19: 3557-3565, 2010.
|
|
|
|
|
|
[PubMed: 20639393]
|
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|
|
[Full Text: https://doi.org/10.1093/hmg/ddq271]
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bitner-Glindzicz, M., Lindley, K. J., Rutland, P., Blaydon, D., Smith, V. V., Milla, P. J., Hussain, K., Furth-Lavi, J., Cosgrove, K. E., Shepherd, R. M., Barnes, P. D., O'Brien, R. E., Farndon, P. A., Sowden, J., Liu, X.-Z., Scanlan, M. J., Malcolm, S., Dunne, M. J., Aynsley-Green, A., Glaser, B.
|
|
<strong>A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C gene.</strong>
|
|
Nature Genet. 26: 56-60, 2000.
|
|
|
|
|
|
[PubMed: 10973248]
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|
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|
|
[Full Text: https://doi.org/10.1038/79178]
|
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</p>
|
|
</li>
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
Blaydon, D. C., Mueller, R. F., Hutchin, T. P., Leroy, B. P., Bhattacharya, S. S., Bird, A. C., Malcolm, S., Bitner-Glindzicz, M.
|
|
<strong>The contribution of USH1C mutations to syndromic and non-syndromic deafness in the UK.</strong>
|
|
Clin. Genet. 63: 303-307, 2003.
|
|
|
|
|
|
[PubMed: 12702164]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.2003.00058.x]
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Boeda, B., El-Amraoui, A., Bahloul, A., Goodyear, R., Daviet, L., Blanchard, S., Perfettini, I., Fath, K. R., Shorte, S., Reiners, J., Houdusse, A., Legrain, P., Wolfrum, U., Richardson, G., Petit, C.
|
|
<strong>Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle.</strong>
|
|
EMBO J. 21: 6689-6699, 2002.
|
|
|
|
|
|
[PubMed: 12485990]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/emboj/cdf689]
|
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|
|
</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, J.-M., Chuzhanova, N., Stenson, P. D., Ferec, C., Cooper, D. N.
|
|
<strong>Meta-analysis of gross insertions causing human genetic disease: novel mutational mechanisms and the role of replication slippage.</strong>
|
|
Hum. Mutat. 25: 207-221, 2005. Note: Erratum: Hum. Mutat. 25: 318 only, 2005.
|
|
|
|
|
|
[PubMed: 15643617]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20133]
|
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|
|
</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Johnson, K. R., Gagnon, L. H., Webb, L. S., Peters, L. L., Hawes, N. L., Chang, B., Zheng, Q. Y.
|
|
<strong>Mouse models of USH1C and DFNB18: phenotypic and molecular analyses of two new spontaneous mutations of the Ush1c gene.</strong>
|
|
Hum. Molec. Genet. 12: 3075-3086, 2003.
|
|
|
|
|
|
[PubMed: 14519688]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddg332]
|
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|
|
</p>
|
|
</li>
|
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Khateb, S., Zelinger, L., Ben-Yosef, T., Merin, S., Crystal-Shalit, O., Gross, M., Banin, E., Sharon, D.
|
|
<strong>Exome sequencing identifies a founder frameshift mutation in an alternative exon of USH1C as the cause of autosomal recessive retinitis pigmentosa with late-onset hearing loss.</strong>
|
|
PLoS One 7: e51566, 2012. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 23251578]
|
|
|
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|
|
[Full Text: https://doi.org/10.1371/journal.pone.0051566]
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|
</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Le Quesne Stabej, P., Saihan, Z., Rangesh, N., Steele-Stallard, H. B., Ambrose, J., Coffey, A., Emmerson, J., Haralambous, E., Hughes, Y., Steel, K. P., Luxon, L. M., Webster, A. R., Bitner-Glindzicz, M.
|
|
<strong>Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study.</strong>
|
|
J. Med. Genet. 49: 27-36, 2012.
|
|
|
|
|
|
[PubMed: 22135276]
|
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