5488 lines
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Entry
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- *608400 - USHERIN; USH2A
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*608400</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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<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
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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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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/608400">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>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000042781;t=ENST00000307340" 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=7399" 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=608400" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000042781;t=ENST00000307340" 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_007123,NM_206933" 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_206933" 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=608400" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=09759&isoform_id=09759_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/USH2A" 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/8515086,19584002,44804677,91207975,913524351,1796365450,1796787041,2402698007" 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/O75445" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=7399" 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=ENSG00000042781;t=ENST00000307340" 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=USH2A" 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=USH2A" 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+7399" 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/USH2A" 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:7399" 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/7399" 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=chr1&hgg_gene=ENST00000307340.8&hgg_start=215622891&hgg_end=216423448&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:12601" 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:12601" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/ush2a" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=608400[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=608400[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/USH2A/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000042781" 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=USH2A" 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=USH2A" 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=USH2A" 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/USH2A" title="Retinal and hearing impairment genetic mutation database USH2A" 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/ush2amut.htm" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Mutations of the USH2a Gene</a></div><div style="margin-left: 0.5em;"><a href="http://www.umd.be/USH2A/" title="The UMD USH2A mutations database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">The UMD USH2A mutations da…</a></div><div style="margin-left: 0.5em;"><a href="https://research.cchmc.org/LOVD2/home.php?select_db=USH2A" 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=USH2A&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/PA37228" 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:12601" 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://www.mousephenotype.org/data/genes/MGI:1341292" 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/USH2A#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:1341292" 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/7399/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA002624/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=7399" 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-060503-794" 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=USH2A&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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608400
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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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USHERIN; USH2A
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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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USH2A GENE<br />
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USH2; US2
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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=USH2A" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">USH2A</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/1/1707?start=-3&limit=10&highlight=1707">1q41</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:215622891-216423448&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'})">1:215,622,891-216,423,448</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>
|
|
<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>
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|
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=613809,276901" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</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>
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Inheritance
|
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</th>
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<th>
|
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Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
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</thead>
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<tbody>
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|
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<tr>
|
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<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/1/1707?start=-3&limit=10&highlight=1707">
|
|
1q41
|
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</a>
|
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</span>
|
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</td>
|
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|
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<td>
|
|
<span class="mim-font">
|
|
Retinitis pigmentosa 39
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/613809"> 613809 </a>
|
|
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
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</td>
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</tr>
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
Usher syndrome, type 2A
|
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|
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</span>
|
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</td>
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<p>Usherin is a transmembrane protein expressed in various tissues including retinal photoreceptors and cochlear hair cells, with a crucial role in photoreceptor survival and cochlear development (summary by <a href="#14" class="mim-tip-reference" title="Jung, S., Park, Y. C., Lee, D., Kim, S., Kim, S.-M., Kim, Y., Lee, D., Hyun, J., Koh, I., Lee, J.-Y. <strong>Exome sequencing identified five novel USH2A variants in Korean patients with retinitis pigmentosa.</strong> Ophthalmic Genet. 44: 163-170, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36314366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36314366</a>] [<a href="https://doi.org/10.1080/13816810.2022.2138456" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36314366">Jung et al., 2023</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36314366" 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>From the Usher syndrome type IIa (<a href="/entry/276901">276901</a>) critical region on chromosome 1 established by linkage studies, <a href="#12" class="mim-tip-reference" title="Eudy, J. D., Weston, M. D., Yao, S., Hoover, D. M., Rehm, H. L., Ma-Edmonds, M., Yan, D., Ahmad, I., Cheng, J. J., Ayuso, C., Cremers, C., Davenport, S., Moller, C., Talmadge, C. B., Beisel, K. W., Tamayo, M., Morton, C. C., Swaroop, A., Kimberling, W. J., Sumegi, J. <strong>Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa.</strong> Science 280: 1753-1757, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9624053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9624053</a>] [<a href="https://doi.org/10.1126/science.280.5370.1753" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9624053">Eudy et al. (1998)</a> identified the USH2A gene and isolated the corresponding cDNA from a human retina cDNA library. The USH2A gene encodes a 1,551-amino acid protein with a predicted molecular mass of 171.5 kD. Northern blot analysis identified 3 mRNA transcripts of 6.5, 5.0, and 1.9 kb in the retina. Reverse transcriptase PCR identified expression of USH2A in human fetal cochlea, eye, brain, and kidney. The USH2A protein sequence contains laminin epidermal growth factor and fibronectin type III motifs, which are most commonly observed in proteins comprising components of the basal lamina and extracellular matrices and in cell adhesion molecules. In the eye, both Bruch membrane (a specialized basement membrane underlying the retinal pigment epithelium) and the interphotoreceptor cell matrix are rich in extracellular matrix proteins. Extracellular matrix proteins also play a fundamental role in the cochlea: COL1A2 (<a href="/entry/120160">120160</a>), COL2A1 (<a href="/entry/120140">120140</a>), and COL3A1 (<a href="/entry/120180">120180</a>) are highly expressed in the membranous labyrinth of the cochlea. In addition, both X-linked and autosomal forms of Alport syndrome (see <a href="/entry/104200">104200</a>) are caused by mutations in collagen type IV genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9624053" 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="#29" class="mim-tip-reference" title="Weston, M. D., Eudy, J. D., Fujita, S., Yao, S.-F., Usami, S., Cremers, C., Greenburg, J., Ramesar, R., Martini, A., Moller, C., Smith, R. J., Sumegi, J., Kimberling, W. J. <strong>Genomic structure and identification of novel mutations in usherin, the gene responsible for Usher syndrome type IIa.</strong> Am. J. Hum. Genet. 66: 1199-1210, 2000. Note: Erratum: Am. J. Hum. Genet. 66: 2020 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10729113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10729113</a>] [<a href="https://doi.org/10.1086/302855" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10729113">Weston et al. (2000)</a> found a sequence difference in the USH2A gene, resulting in reduction of the total length of the encoded protein, which they designated usherin, from 1,551 to 1,546 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10729113" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Huang, D., Eudy, J. D., Uzvolgyi, E., Davis, J. R., Talmadge, C. B., Pretto, D., Weston, M. D., Lehman, J. E., Zhou, M., Seemayer, T. A., Ahmad, I., Kimberling, W. J., Sumegi, J. <strong>Identification of the mouse and rat orthologs of the gene mutated in Usher syndrome type IIA and the cellular source of USH2A mRNA in retina, a target tissue of the disease.</strong> Genomics 80: 195-203, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12160733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12160733</a>] [<a href="https://doi.org/10.1006/geno.2002.6823" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12160733">Huang et al. (2002)</a> isolated and characterized the mouse and rat orthologs of human USH2A. Like human USH2A, the mouse and rat genes are expressed primarily in retina and cochlea. Mouse Ush2a encodes a 161-kD protein that shows 68% identity and 9% similarity to the human USH2A protein. The predicted amino acid sequence of the mouse and rat proteins, like their human counterpart, contain a leader sequence, an amino-terminal globular domain, 10 laminin epidermal growth factor domains, and 4 carboxy-terminal fibronectin type III motifs. With in situ hybridization, the authors compared the cellular expression of the USH2A gene in rat, mouse, and human retinas. In all 3 species, Ush2a mRNA was expressed in cells of the outer nuclear layer of the retina, one of the target tissues of the disease. In the developing rat retina, Ush2a mRNA expression appeared in the neuroepithelium at embryonic day 17. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12160733" 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="#28" class="mim-tip-reference" title="van Wijk, E., Pennings, R. J. E., te Brinke, H., Claassen, A., Yntema, H. G., Hoefsloot, L. H., Cremers, F. P. M., Cremers, C. W. R. J., Kremer, H. <strong>Identification of 51 novel exons of the Usher syndrome type 2A (USH2A) gene that encode multiple conserved functional domains and that are mutated in patients with Usher syndrome type II.</strong> Am. J. Hum. Genet. 74: 738-744, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15015129/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15015129</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15015129[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/383096" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15015129">Van Wijk et al. (2004)</a> identified novel exons in the USH2A gene and obtained evidence for alternative splicing. The putative 5,202-residue protein encoded by the longest open reading frame harbors, in addition to the known functional domains, 2 laminin G and 28 fibronectin type III repeats, as well as a transmembrane region followed by an intracellular domain with a PDZ-binding domain at its C-terminal end. Semiquantitative expression profile analysis suggested a low level of expression for both the long and the short isoform(s) and partial overlap in spatial and temporal expression patterns. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15015129" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using immunofluorescence microscopy in mouse retina, <a href="#17" class="mim-tip-reference" title="Liu, X., Bulgakov, O. V., Darrow, K. N., Pawlyk, B., Adamian, M., Liberman, M. C., Li, T. <strong>Usherin is required for maintenance of retinal photoreceptors and normal development of cochlear hair cells.</strong> Proc. Nat. Acad. Sci. 104: 4413-4418, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17360538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17360538</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17360538[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.0610950104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17360538">Liu et al. (2007)</a> localized usherin to the apical inner segment recess that wraps around the connecting cilia, which links the inner and outer photoreceptor segments. Usherin also associated transiently with hair bundles in hair cells of the cochlea during early postnatal mouse development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17360538" 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="#29" class="mim-tip-reference" title="Weston, M. D., Eudy, J. D., Fujita, S., Yao, S.-F., Usami, S., Cremers, C., Greenburg, J., Ramesar, R., Martini, A., Moller, C., Smith, R. J., Sumegi, J., Kimberling, W. J. <strong>Genomic structure and identification of novel mutations in usherin, the gene responsible for Usher syndrome type IIa.</strong> Am. J. Hum. Genet. 66: 1199-1210, 2000. Note: Erratum: Am. J. Hum. Genet. 66: 2020 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10729113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10729113</a>] [<a href="https://doi.org/10.1086/302855" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10729113">Weston et al. (2000)</a> determined that the usherin gene contains 21 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10729113" 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="#28" class="mim-tip-reference" title="van Wijk, E., Pennings, R. J. E., te Brinke, H., Claassen, A., Yntema, H. G., Hoefsloot, L. H., Cremers, F. P. M., Cremers, C. W. R. J., Kremer, H. <strong>Identification of 51 novel exons of the Usher syndrome type 2A (USH2A) gene that encode multiple conserved functional domains and that are mutated in patients with Usher syndrome type II.</strong> Am. J. Hum. Genet. 74: 738-744, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15015129/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15015129</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15015129[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/383096" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15015129">Van Wijk et al. (2004)</a> identified 51 additional exons at the 3-prime end of the USH2A gene, bringing the total number of exons to 72, and <a href="#1" class="mim-tip-reference" title="Adato, A., Lefevre, G., Delprat, B., Michel, V., Michalski, N., Chardenoux, S., Weil, D., El-Amraoui, A., Petit, C. <strong>Usherin, the defective protein in Usher syndrome type IIA, is likely to be a component of interstereocilia ankle links in the inner ear sensory cells.</strong> Hum. Molec. Genet. 14: 3921-3932, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16301217/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16301217</a>] [<a href="https://doi.org/10.1093/hmg/ddi416" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16301217">Adato et al. (2005)</a> described a new alternatively spliced exon 71. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16301217+15015129" 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 fluorescence in situ hybridization, <a href="#13" class="mim-tip-reference" title="Huang, D., Eudy, J. D., Uzvolgyi, E., Davis, J. R., Talmadge, C. B., Pretto, D., Weston, M. D., Lehman, J. E., Zhou, M., Seemayer, T. A., Ahmad, I., Kimberling, W. J., Sumegi, J. <strong>Identification of the mouse and rat orthologs of the gene mutated in Usher syndrome type IIA and the cellular source of USH2A mRNA in retina, a target tissue of the disease.</strong> Genomics 80: 195-203, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12160733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12160733</a>] [<a href="https://doi.org/10.1006/geno.2002.6823" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12160733">Huang et al. (2002)</a> mapped the mouse Ush2a gene to chromosome 1 in a region syntenic to human chromosome 1q41. Rat Ush2a was localized by radiation hybrid analysis to rat chromosome 13. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12160733" 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="#1" class="mim-tip-reference" title="Adato, A., Lefevre, G., Delprat, B., Michel, V., Michalski, N., Chardenoux, S., Weil, D., El-Amraoui, A., Petit, C. <strong>Usherin, the defective protein in Usher syndrome type IIA, is likely to be a component of interstereocilia ankle links in the inner ear sensory cells.</strong> Hum. Molec. Genet. 14: 3921-3932, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16301217/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16301217</a>] [<a href="https://doi.org/10.1093/hmg/ddi416" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16301217">Adato et al. (2005)</a> described usherin alternative transcripts in the murine inner ear encoding several predicted transmembrane usherin isoforms with modular ectodomains of different lengths. They identified a 24-amino acid peptide, encoded by a novel exon, within the cytoplasmic region and found it to be predominantly expressed in the inner ear but not in the retina. In mouse and rat inner ears, a transmembrane usherin was present at the base of the differentiating stereocilia, which make up the mechanosensitive hair bundles receptive to sound. Usherin immunolabeling was transient in the hair bundles of cochlear hair cells (HCs), but persisted in mature hair bundles of vestibular HCs. Coimmunoprecipitation and in vitro binding assays demonstrated that the usherin cytodomain can bind to whirlin (WHRN; <a href="/entry/607928">607928</a>) and harmonin (USH1C; <a href="/entry/605242">605242</a>), 2 PDZ domain-containing proteins that are defective in genetic forms of isolated deafness (see <a href="/entry/607084">607084</a>) and Usher type IC (<a href="/entry/276904">276904</a>), respectively. These PDZ proteins are suitable to provide the anchoring of interstereocilia lateral links to the F-actin core of stereocilia. The authors suggested that congenital deafness in Usher types I and II (see <a href="/entry/276901">276901</a>) shares similar pathogenic mechanisms, i.e., the disruption of hair bundle links-mediated adhesion forces that are essential for the proper organization of growing hair bundles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16301217" 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="#23" 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, 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>By yeast 2-hybrid analysis using deletion constructs of lebercilin (<a href="/entry/611408">611408</a>) and the intracellular region of USH2A isoform B, <a href="#27" class="mim-tip-reference" title="van Wijk, E., Kersten, F. F. J., Kartono, A., Mans, D. A., Brandwijk, K., Letteboer, S. J. F., Peters, T. A., Marker, T., Yan, X., Cremers, C. W. R. J., Cremers, F. P. M., Wolfrum, U., Roepman, R., Kremer, H. <strong>Usher syndrome and Leber congenital amaurosis are molecularly linked via a novel isoform of the centrosomal ninein-like protein.</strong> Hum. Molec. Genet. 18: 51-64, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18826961/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18826961</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18826961[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/ddn312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18826961">van Wijk et al. (2009)</a> showed that the intermediate filament region of NLP(isoB) (NINL; <a href="/entry/609580">609580</a>) interacts with lebercilin and USH2A(isoB), whereas no interaction was detected for NLP(isoA). Coimmunoprecipitation and GST pull-down assays confirmed interaction between NLP(isoB) and lebercilin and USH2A. Recombinant NLP(isoB), lebercilin, and USH2A(isoB) were all found to colocalize at the centrosomes in human retinal pigment epithelial (ARPE-19) cells. Staining of adult rat retinal sections with specific antibodies against all 3 proteins revealed their colocalization at the basal bodies of the photoreceptor-connecting cilia. A truncation mutation (<a href="/entry/611408#0003">611408.0003</a>) in lebercilin reduced interaction and colocalization with NLP(isoB); however, RNAi knockdown of both endogenous NLP and lebercilin in ciliated ARPE-19 cells did not result in altered protein localization of NLP or lebercilin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18826961" 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 coimmunoprecipitation studies, <a href="#11" class="mim-tip-reference" title="Ebermann, I., Phillips, J. B., Liebau, M. C., Koenekoop, R. K., Schermer, B., Lopez, I., Schafer, E., Roux, A.-F., Dafinger, C., Bernd, A., Zrenner, E., Claustres, M., Blanco, B., Nurnberg, G., Nurnberg, P., Ruland, R., Westerfield, M., Benzing, T., Bolz, H. J. <strong>PDZD7 is a modifier of retinal disease and a contributor to digenic Usher syndrome.</strong> J. Clin. Invest. 120: 1812-1823, 2010. Note: Erratum: J. Clin. Invest. 121: 821 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20440071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20440071</a>] [<a href="https://doi.org/10.1172/JCI39715" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20440071">Ebermann et al. (2010)</a> demonstrated interaction of USH2A with the first and second PDZ domains of PDZD7 (<a href="/entry/612971">612971</a>); a truncated version of USH2A without the C-terminal PDZ-binding motif showed reduced interaction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20440071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Usher Syndrome Type IIA</em></strong></p><p>
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Among 96 patients with Usher syndrome type IIa (<a href="/entry/276901">276901</a>), <a href="#12" class="mim-tip-reference" title="Eudy, J. D., Weston, M. D., Yao, S., Hoover, D. M., Rehm, H. L., Ma-Edmonds, M., Yan, D., Ahmad, I., Cheng, J. J., Ayuso, C., Cremers, C., Davenport, S., Moller, C., Talmadge, C. B., Beisel, K. W., Tamayo, M., Morton, C. C., Swaroop, A., Kimberling, W. J., Sumegi, J. <strong>Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa.</strong> Science 280: 1753-1757, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9624053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9624053</a>] [<a href="https://doi.org/10.1126/science.280.5370.1753" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9624053">Eudy et al. (1998)</a> identified 3 mutations in the USH2A gene (<a href="#0001">608400.0001</a>-<a href="#0003">608400.0003</a>), all of which resulted in frameshifts and premature terminations. A 2299delG mutation (<a href="#0001">608400.0001</a>), originally reported as 2314delG, was the most frequent mutant allele, occurring in 21 cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9624053" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a mutation search of 57 independent USH2A probands, <a href="#29" class="mim-tip-reference" title="Weston, M. D., Eudy, J. D., Fujita, S., Yao, S.-F., Usami, S., Cremers, C., Greenburg, J., Ramesar, R., Martini, A., Moller, C., Smith, R. J., Sumegi, J., Kimberling, W. J. <strong>Genomic structure and identification of novel mutations in usherin, the gene responsible for Usher syndrome type IIa.</strong> Am. J. Hum. Genet. 66: 1199-1210, 2000. Note: Erratum: Am. J. Hum. Genet. 66: 2020 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10729113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10729113</a>] [<a href="https://doi.org/10.1086/302855" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10729113">Weston et al. (2000)</a> identified 15 mutations in the USH2A gene. Of 114 independent USH2A alleles, 58 harbored probable pathologic mutations. Ten cases were true homozygotes and 10 were compound heterozygotes; 18 heterozygotes with only 1 identifiable mutation were observed. The 2299delG allele was the most frequent mutant allele, observed in 31 of 192 alleles (16%). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10729113" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Dreyer, B., Tranebjaerg, L., Rosenberg, T., Weston, M. D., Kimberling, W. J., Nilssen, O. <strong>Identification of novel USH2A mutations: implications for the structure of USH2A protein.</strong> Europ. J. Hum. Genet. 8: 500-506, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10909849/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10909849</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200491" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10909849">Dreyer et al. (2000)</a> screened the USH2A gene for mutations in 31 unrelated patients from Denmark and Norway with Usher syndrome type II. The 2299delG mutation accounted for 44% of disease alleles. They found 16 novel putative disease-causing mutations, of which 12 were private and 4 were shared by unrelated patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10909849" 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 unrelated patients with Usher syndrome, each with 1 mutation in exons 1 to 21 of the USH2A gene, <a href="#28" class="mim-tip-reference" title="van Wijk, E., Pennings, R. J. E., te Brinke, H., Claassen, A., Yntema, H. G., Hoefsloot, L. H., Cremers, F. P. M., Cremers, C. W. R. J., Kremer, H. <strong>Identification of 51 novel exons of the Usher syndrome type 2A (USH2A) gene that encode multiple conserved functional domains and that are mutated in patients with Usher syndrome type II.</strong> Am. J. Hum. Genet. 74: 738-744, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15015129/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15015129</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15015129[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/383096" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15015129">van Wijk et al. (2004)</a> identified a second pathogenic USH2A mutation in the 51 additional USH2A exons that they identified. The novel mutations included 3 different truncating mutations and 2 missense mutations (see, .e.g., <a href="#0007">608400.0007</a>-<a href="#0009">608400.0009</a>). The presence of pathogenic mutations in the novel exons indicated that at least 1 of the putative long isoforms of the USH2A protein plays a role in both hearing and vision. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15015129" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Aller, E., Jaijo, T., Beneyto, M., Najera, C., Oltra, S., Ayuso, C., Baiget, M., Carballo, M., Antinolo, G., Valverde, D., Moreno, F., Vilela, C., Collado, D., Perez-Garrigues, H., Navea, A., Millan, J. M. <strong>Identification of 14 novel mutations in the long isoform of USH2A in Spanish patients with Usher syndrome type II.</strong> J. Med. Genet. 43: e55, 2006. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17085681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17085681</a>] [<a href="https://doi.org/10.1136/jmg.2006.041764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17085681">Aller et al. (2006)</a> identified mutations in the USH2A gene in 14 of 32 unrelated Spanish patients with Usher syndrome, nonsyndromic retinal degeneration, or nonsyndromic deafness in whom 2 disease-causing mutations could not be found after screening the first 21 exons of the USH2A gene. Analysis of the 51 new exons identified by <a href="#28" class="mim-tip-reference" title="van Wijk, E., Pennings, R. J. E., te Brinke, H., Claassen, A., Yntema, H. G., Hoefsloot, L. H., Cremers, F. P. M., Cremers, C. W. R. J., Kremer, H. <strong>Identification of 51 novel exons of the Usher syndrome type 2A (USH2A) gene that encode multiple conserved functional domains and that are mutated in patients with Usher syndrome type II.</strong> Am. J. Hum. Genet. 74: 738-744, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15015129/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15015129</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15015129[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/383096" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15015129">van Wijk et al. (2004)</a> and the 1 new exon identified by <a href="#1" class="mim-tip-reference" title="Adato, A., Lefevre, G., Delprat, B., Michel, V., Michalski, N., Chardenoux, S., Weil, D., El-Amraoui, A., Petit, C. <strong>Usherin, the defective protein in Usher syndrome type IIA, is likely to be a component of interstereocilia ankle links in the inner ear sensory cells.</strong> Hum. Molec. Genet. 14: 3921-3932, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16301217/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16301217</a>] [<a href="https://doi.org/10.1093/hmg/ddi416" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16301217">Adato et al. (2005)</a> yielded 14 novel mutations, including 7 missense, 5 frameshift, 1 duplication, and 1 putative splice site mutation. Most of the patients had previously been reported by <a href="#3" class="mim-tip-reference" title="Aller, E., Najera, C., Millan, J. M., Oltra, J. S., Perez-Garrigues, H., Vilela, C., Navea, A., Beneyto, M. <strong>Genetic analysis of 2299delG and C759F mutations (USH2A) in patients with visual and/or auditory impairments.</strong> Europ. J. Hum. Genet. 12: 407-410, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14970843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14970843</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201138" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14970843">Aller et al. (2004)</a>. All of the individuals with 2 mutations were clinically diagnosed with Usher syndrome type IIa. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17085681+16301217+14970843+15015129" 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="Baux, D., Larrieu, L., Blanchet, C., Hamel. C., Ben Salah, S., Vielle, A., Gilbert-Dussardier, B., Holder, M., Calvas, P., Philip, N., Edery, P., Bonneau, D., Claustres, M., Malcolm, S., Roux, A.-F. <strong>Molecular and in silico analyses of the full-length isoform of usherin identify new pathogenic alleles in Usher type II patients.</strong> Hum. Mutat. 28: 781-789, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17405132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17405132</a>] [<a href="https://doi.org/10.1002/humu.20513" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17405132">Baux et al. (2007)</a> identified 34 distinct mutations in the USH2A gene in affected individuals from 25 families with Usher syndrome. Two of the alleles were complex with 3 and 2 mutations in cis, respectively. Only 5 families carried both mutations in the first 21 exons, indicating that screening of the entire gene is necessary for accurate and complete mutational analysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17405132" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To explore the spectrum of USH2A disease-causing mutations among Scandinavian USH2 cases, <a href="#7" class="mim-tip-reference" title="Dreyer, B., Brox, V., Tranebjaerg, L., Rosenberg, T., Sadeghi, A. M., Moller, C., Nilssen, O. <strong>Spectrum of USH2A mutations in Scandinavian patients with Usher syndrome type II.</strong> Hum. Mutat. 29: 451 only, 2008. Note: Full article online.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18273898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18273898</a>] [<a href="https://doi.org/10.1002/humu.9524" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18273898">Dreyer et al. (2008)</a> performed extensive DNA sequence analysis of the full-size USH2A gene in patients from 118 unrelated families, of which 27 had previously been found to carry mutations in exons 1 to 21. In all, 122 USH2A DNA sequence alterations were identified, of which 57 were predicted to be pathogenic, 7 were considered to be of uncertain pathogenicity, and 58 were predicted to be benign variants. Of 36 novel pathogenic USH2A mutations, 31 were located in exons 22 to 73, specific to the long isoform (see, e.g., <a href="#0013">608400.0013</a>). USH2A mutations were identified in 89 (75.4%) of 118 families. In 79 (88.8%) of these 89 families, 2 pathogenic mutations were identified, whereas in 10 families (11.2%) the second mutation remained unidentified. In 5 (4.2%) of the 118 families the USH phenotype could be explained by mutations in the CLRN1 gene (<a href="/entry/606397">606397</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18273898" 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="#30" class="mim-tip-reference" title="Yan, D., Ouyang, X., Patterson, D. M., Du, L. L., Jacobson, S. G., Liu, X.-Z. <strong>Mutation analysis in the long isoform of USH2A in American patients with Usher syndrome type II.</strong> J. Hum. Genet. 54: 732-738, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19881469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19881469</a>] [<a href="https://doi.org/10.1038/jhg.2009.107" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19881469">Yan et al. (2009)</a> identified mutant USH2A alleles in 12 (60%) of 20 American patients of European ancestry with Usher syndrome type IIa. Seven (35%) patients had only 1 pathogenic mutation, and 8 patients did not have USH2A mutations. There were 5 novel mutations and 5 previously reported mutations, consisting of 3 missense, 3 frameshift, and 4 nonsense. The 2299delG mutation was the most common, accounting for 38.9% of mutant alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19881469" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="McGee, T. L., Seyedahmadi, B. J., Sweeney, M. O., Dryja, T. P., Berson, E. L. <strong>Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome type II or non-syndromic retinitis pigmentosa.</strong> J. Med. Genet. 47: 499-506, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20507924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20507924</a>] [<a href="https://doi.org/10.1136/jmg.2009.075143" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20507924">McGee et al. (2010)</a> screened the long isoform of USH2A in 108 patients diagnosed with Usher syndrome type IIa and identified at least 1 deleterious mutation in at least 57% of cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20507924" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Retinitis Pigmentosa 39</em></strong></p><p>
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<a href="#24" class="mim-tip-reference" title="Rivolta, C., Berson, E. L., Dryja, T. P. <strong>Paternal uniparental heterodisomy with partial isodisomy of chromosome 1 in a patient with retinitis pigmentosa without hearing loss and a missense mutation in the Usher syndrome type II gene USH2A.</strong> Arch. Ophthal. 120: 1566-1571, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12427073/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12427073</a>] [<a href="https://doi.org/10.1001/archopht.120.11.1566" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12427073">Rivolta et al. (2002)</a> identified autosomal recessive retinitis pigmentosa (RP39; <a href="/entry/613809">613809</a>) without hearing loss due to mutation in the USH2A gene inherited by uniparental paternal disomy (C759F; <a href="#0006">608400.0006</a>). <a href="#31" class="mim-tip-reference" title="Zlotogora, J. <strong>Parents of children with autosomal recessive diseases are not always carriers of the respective mutant alleles.</strong> Hum. Genet. 114: 521-526, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15024643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15024643</a>] [<a href="https://doi.org/10.1007/s00439-004-1105-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15024643">Zlotogora (2004)</a> reviewed examples in which uniparental disomy had been established as the cause of an autosomal recessive disorder. One of 6 such disorders listed for chromosome 1, the most for any single chromosome, was autosomal recessive retinitis pigmentosa without hearing loss due to mutation in the USH2A gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15024643+12427073" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="McGee, T. L., Seyedahmadi, B. J., Sweeney, M. O., Dryja, T. P., Berson, E. L. <strong>Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome type II or non-syndromic retinitis pigmentosa.</strong> J. Med. Genet. 47: 499-506, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20507924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20507924</a>] [<a href="https://doi.org/10.1136/jmg.2009.075143" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20507924">McGee et al. (2010)</a> screened the long isoform of USH2A in 80 patients with nonsyndromic autosomal recessive RP and identified at least 1 deleterious mutation in 19% of cases. The authors stated that their findings supported USH2A as the most common known cause of RP in the United States. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20507924" 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 cohort of 94 Korean probands with RP, <a href="#14" class="mim-tip-reference" title="Jung, S., Park, Y. C., Lee, D., Kim, S., Kim, S.-M., Kim, Y., Lee, D., Hyun, J., Koh, I., Lee, J.-Y. <strong>Exome sequencing identified five novel USH2A variants in Korean patients with retinitis pigmentosa.</strong> Ophthalmic Genet. 44: 163-170, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36314366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36314366</a>] [<a href="https://doi.org/10.1080/13816810.2022.2138456" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36314366">Jung et al. (2023)</a> analyzed the USH2A gene and identified 10 probands who were compound heterozygous for mutations in the USH2A gene (e.g., <a href="#0016">608400.0016</a>-<a href="#0018">608400.0018</a>). Hearing tests were not performed because no hearing problems were reported by any of the probands. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36314366" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Cosegregation of Usher Syndrome and Retinitis Pigmentosa</em></strong></p><p>
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In a consanguineous family of Iraqi Jewish origin in which some members had USH2 and others had nonsyndromic retinitis pigmentosa, <a href="#15" class="mim-tip-reference" title="Kaiserman, N., Obolensky, A., Banin, E., Sharon, D. <strong>Novel USH2A mutations in Israeli patients with retinitis pigmentosa and Usher syndrome type 2.</strong> Arch. Ophthal. 125: 219-224, 2007. Note: Erratum: Arch. Ophthal. 125: 1013, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17296898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17296898</a>] [<a href="https://doi.org/10.1001/archopht.125.2.219" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17296898">Kaiserman et al. (2007)</a> identified 3 pathogenic mutations in the USH2A gene. Patients with USH2A were compound heterozygous for 2 null mutations (<a href="#0010">608400.0010</a>-<a href="#0011">608400.0011</a>), whereas patients with nonsyndromic RP were compound heterozygous for 1 of the null mutations and a novel missense mutation (<a href="#0012">608400.0012</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17296898" 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>To investigate genotype/phenotype correlations, <a href="#3" class="mim-tip-reference" title="Aller, E., Najera, C., Millan, J. M., Oltra, J. S., Perez-Garrigues, H., Vilela, C., Navea, A., Beneyto, M. <strong>Genetic analysis of 2299delG and C759F mutations (USH2A) in patients with visual and/or auditory impairments.</strong> Europ. J. Hum. Genet. 12: 407-410, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14970843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14970843</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201138" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14970843">Aller et al. (2004)</a> screened 191 unrelated Spanish patients with syndromic or nonsyndromic retinal diseases, or with nonsyndromic hearing impairment, for the 2299delG (<a href="#0001">608400.0001</a>) and C759F (<a href="#0006">608400.0006</a>) mutations in the USH2A gene. They found that the 2299delG mutation was present in patients with clinical signs of Usher syndrome type II or of atypical Usher syndrome, whereas the C759F mutation, whether or not it was associated with the 2299delG mutation, was identified in cases with nonsyndromic retinitis pigmentosa (RP). <a href="#3" class="mim-tip-reference" title="Aller, E., Najera, C., Millan, J. M., Oltra, J. S., Perez-Garrigues, H., Vilela, C., Navea, A., Beneyto, M. <strong>Genetic analysis of 2299delG and C759F mutations (USH2A) in patients with visual and/or auditory impairments.</strong> Europ. J. Hum. Genet. 12: 407-410, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14970843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14970843</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201138" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14970843">Aller et al. (2004)</a> concluded that sensorineural hearing loss in patients with RP may depend on the nature and association of the USH2A allelic variants present. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14970843" 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="Bernal, S., Meda, C., Solans, T., Ayuso, C., Garcia-Sandoval, B., Valverde, D., Del Rio, E., Baiget, M. <strong>Clinical and genetic studies in Spanish patients with Usher syndrome type II: description of new mutations and evidence for a lack of genotype-phenotype correlation.</strong> Clin. Genet. 68: 204-214, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16098008/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16098008</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2005.00481.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16098008">Bernal et al. (2005)</a> studied 28 Spanish patients with Usher syndrome type II, identifying 10 different pathogenic mutations and 17 polymorphisms in the USH2A gene. They observed discordant phenotypes in sib pairs from 2 unrelated families and noted that <a href="#18" class="mim-tip-reference" title="Liu, X.-Z., Hope, C., Liang, C. Y., Zou, J. M., Xu, L. R., Cole, T., Mueller, R. F., Bundey, S., Nance, W., Steel, K. P., Brown, S. D. M. <strong>A mutation (2314delG) in the Usher syndrome type IIA gene: high prevalence and phenotypic variation. (Letter)</strong> Am. J. Hum. Genet. 64: 1221-1225, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10090909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10090909</a>] [<a href="https://doi.org/10.1086/302332" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10090909">Liu et al. (1999)</a> had reported clinical differences in monozygotic twins with Usher syndrome type II and had suggested that variation in the expression of the USH2A gene is not determined simply by genetic factors. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10090909+16098008" 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="#17" class="mim-tip-reference" title="Liu, X., Bulgakov, O. V., Darrow, K. N., Pawlyk, B., Adamian, M., Liberman, M. C., Li, T. <strong>Usherin is required for maintenance of retinal photoreceptors and normal development of cochlear hair cells.</strong> Proc. Nat. Acad. Sci. 104: 4413-4418, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17360538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17360538</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17360538[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.0610950104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17360538">Liu et al. (2007)</a> found that Ush2a knockout in mice led to progressive photoreceptor degeneration and a moderate but nonprogressive hearing impairment, mimicking the visual and hearing defects in USH2A patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17360538" 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> rs80338903 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338903;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/rs80338903?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=rs80338903" 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=rs80338903" 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=RCV000002445 OR RCV000032524 OR RCV000191141 OR RCV000210326 OR RCV000254870 OR RCV000504641 OR RCV000623326 OR RCV000678639 OR RCV000735362 OR RCV000787895 OR RCV000787897 OR RCV000787899 OR RCV000824793 OR RCV001000453 OR RCV001095692 OR RCV002504737" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002445, RCV000032524, RCV000191141, RCV000210326, RCV000254870, RCV000504641, RCV000623326, RCV000678639, RCV000735362, RCV000787895, RCV000787897, RCV000787899, RCV000824793, RCV001000453, RCV001095692, RCV002504737" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002445...</a>
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<p>By heteroduplex analysis, <a href="#12" class="mim-tip-reference" title="Eudy, J. D., Weston, M. D., Yao, S., Hoover, D. M., Rehm, H. L., Ma-Edmonds, M., Yan, D., Ahmad, I., Cheng, J. J., Ayuso, C., Cremers, C., Davenport, S., Moller, C., Talmadge, C. B., Beisel, K. W., Tamayo, M., Morton, C. C., Swaroop, A., Kimberling, W. J., Sumegi, J. <strong>Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa.</strong> Science 280: 1753-1757, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9624053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9624053</a>] [<a href="https://doi.org/10.1126/science.280.5370.1753" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9624053">Eudy et al. (1998)</a> identified a 2299delG mutation (originally reported by them as 2314delG) in the USH2A gene in 21 of 96 probands with Usher syndrome type IIa (USH2A; <a href="/entry/276901">276901</a>); 8 of them were homozygous and 13 heterozygous. All but 2 were of northern European ancestry (Swedish, Dutch, German, or English). The 2 non-northern European patients were both homozygous for the 2299G deletion; one was from Spain and the other was an African American from Nebraska, U.S. Examination of various haplotypes failed to reveal any substantial disequilibrium with the 2299delG mutation, suggesting that the mutation did not arise in a common ancestor. The 2299delG mutation caused a frameshift at codon 772, after which the open reading frame continued for 20 codons and ended as TAG. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9624053" 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="Liu, X.-Z., Hope, C., Liang, C. Y., Zou, J. M., Xu, L. R., Cole, T., Mueller, R. F., Bundey, S., Nance, W., Steel, K. P., Brown, S. D. M. <strong>A mutation (2314delG) in the Usher syndrome type IIA gene: high prevalence and phenotypic variation. (Letter)</strong> Am. J. Hum. Genet. 64: 1221-1225, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10090909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10090909</a>] [<a href="https://doi.org/10.1086/302332" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10090909">Liu et al. (1999)</a> performed a mutation analysis of the USH2A gene in 23 families with Usher syndrome, 10 of which had a diagnosis of atypical Usher syndrome, from the United Kingdom and China. They found that most of the families with USH2 carried the 2299delG mutation. Of 12 families with the 2299delG mutation, 8 families had the typical USH2 phenotype (congenital moderate to severe hearing impairment, normal vestibular function, and postpubertal onset of retinitis pigmentosa). However, 5 affected individuals from the remaining 4 families carrying the 2299delG mutation showed atypical Usher syndrome features, with progressive hearing impairment, variable vestibular function, and RP. An isolated patient with the mutation was typical of USH2 in all aspects, including nonprogressive hearing loss, but had absent vestibular function, which is a critical discriminator in clinical classification. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10090909" 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="#29" class="mim-tip-reference" title="Weston, M. D., Eudy, J. D., Fujita, S., Yao, S.-F., Usami, S., Cremers, C., Greenburg, J., Ramesar, R., Martini, A., Moller, C., Smith, R. J., Sumegi, J., Kimberling, W. J. <strong>Genomic structure and identification of novel mutations in usherin, the gene responsible for Usher syndrome type IIa.</strong> Am. J. Hum. Genet. 66: 1199-1210, 2000. Note: Erratum: Am. J. Hum. Genet. 66: 2020 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10729113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10729113</a>] [<a href="https://doi.org/10.1086/302855" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10729113">Weston et al. (2000)</a> revised numbering for the sequence of the USH2A gene, taking into account a significant sequence difference. The 2299delG mutation reported by <a href="#12" class="mim-tip-reference" title="Eudy, J. D., Weston, M. D., Yao, S., Hoover, D. M., Rehm, H. L., Ma-Edmonds, M., Yan, D., Ahmad, I., Cheng, J. J., Ayuso, C., Cremers, C., Davenport, S., Moller, C., Talmadge, C. B., Beisel, K. W., Tamayo, M., Morton, C. C., Swaroop, A., Kimberling, W. J., Sumegi, J. <strong>Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa.</strong> Science 280: 1753-1757, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9624053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9624053</a>] [<a href="https://doi.org/10.1126/science.280.5370.1753" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9624053">Eudy et al. (1998)</a> is correctly referred to as 2299delG. The sequence difference reduces the length of the usherin protein from 1551 to 1546 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10729113+9624053" 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="#29" class="mim-tip-reference" title="Weston, M. D., Eudy, J. D., Fujita, S., Yao, S.-F., Usami, S., Cremers, C., Greenburg, J., Ramesar, R., Martini, A., Moller, C., Smith, R. J., Sumegi, J., Kimberling, W. J. <strong>Genomic structure and identification of novel mutations in usherin, the gene responsible for Usher syndrome type IIa.</strong> Am. J. Hum. Genet. 66: 1199-1210, 2000. Note: Erratum: Am. J. Hum. Genet. 66: 2020 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10729113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10729113</a>] [<a href="https://doi.org/10.1086/302855" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10729113">Weston et al. (2000)</a> found the 2299delG mutation to be the most frequent, having a frequency of 31 in 192 alleles (16%) in their series. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10729113" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Dreyer, B., Tranebjaerg, L., Brox, V., Rosenberg, T., Moller, C., Beneyto, M., Weston, M. D., Kimberling, W. J., Nilssen, O. <strong>A common ancestral origin of the frequent and widespread 2299delG USH2A mutation.</strong> Am. J. Hum. Genet. 69: 228-234, 2001. Note: Erratum: Am. J. Hum. Genet. 69: 922 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11402400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11402400</a>] [<a href="https://doi.org/10.1086/321269" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11402400">Dreyer et al. (2001)</a> presented data indicating that the widespread geographic distribution of the 2299delG mutation is the result of an ancestral mutation that spread throughout Europe and into the New World as a result of migration. Various studies had reported a range of frequencies (from 0.16 to 0.44) among patients with Usher syndrome, depending on the geographic origin of the patients. <a href="#8" class="mim-tip-reference" title="Dreyer, B., Tranebjaerg, L., Brox, V., Rosenberg, T., Moller, C., Beneyto, M., Weston, M. D., Kimberling, W. J., Nilssen, O. <strong>A common ancestral origin of the frequent and widespread 2299delG USH2A mutation.</strong> Am. J. Hum. Genet. 69: 228-234, 2001. Note: Erratum: Am. J. Hum. Genet. 69: 922 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11402400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11402400</a>] [<a href="https://doi.org/10.1086/321269" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11402400">Dreyer et al. (2001)</a> performed haplotype analysis on DNA samples from 116 unrelated patients with Usher syndrome type IIa; the patients were from 14 countries and represented 148 2299delG alleles. On the basis of 6 single-nucleotide polymorphisms (SNPs) within the USH2A gene, 12 core haplotypes were observed in a panel of normal chromosomes. However, in their patient analysis, only 1 core haplotype was associated with the 2299delG mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11402400" 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="#20" class="mim-tip-reference" title="Ouyang, X. M., Yan, D., Hejtmancik, J. F., Jacobson, S. G., Li, A. R., Du, L. L., Angeli, S., Kaiser, M., Balkany, T., Liu, X. Z. <strong>Mutational spectrum in Usher syndrome type II.</strong> Clin. Genet. 65: 288-293, 2004. Note: Erratum: Clin. Genet. 65: 433 only, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15025721/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15025721</a>] [<a href="https://doi.org/10.1046/j.1399-0004.2004.00216.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15025721">Ouyang et al. (2004)</a> confirmed that 2299delG is the most common mutation in USH2A, accounting for 77.5% of the pathologic alleles. In 5 of the 24 patients, the 2299delG mutation was present in homozygous state; in 3 it was present in compound heterozygous state with other mutations; and in 16 it was present in heterozygous state. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15025721" 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="Baux, D., Larrieu, L., Blanchet, C., Hamel. C., Ben Salah, S., Vielle, A., Gilbert-Dussardier, B., Holder, M., Calvas, P., Philip, N., Edery, P., Bonneau, D., Claustres, M., Malcolm, S., Roux, A.-F. <strong>Molecular and in silico analyses of the full-length isoform of usherin identify new pathogenic alleles in Usher type II patients.</strong> Hum. Mutat. 28: 781-789, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17405132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17405132</a>] [<a href="https://doi.org/10.1002/humu.20513" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17405132">Baux et al. (2007)</a> identified the 2299delG mutation, which results in a frameshift at codon 767, in 22% of mutated alleles in their study of 25 affected families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17405132" 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="#30" class="mim-tip-reference" title="Yan, D., Ouyang, X., Patterson, D. M., Du, L. L., Jacobson, S. G., Liu, X.-Z. <strong>Mutation analysis in the long isoform of USH2A in American patients with Usher syndrome type II.</strong> J. Hum. Genet. 54: 732-738, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19881469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19881469</a>] [<a href="https://doi.org/10.1038/jhg.2009.107" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19881469">Yan et al. (2009)</a> identified the 2299delG mutation in 38.9% of mutant alleles among 12 American probands of European descent with Usher syndrome type IIa. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19881469" 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">rs397518008 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397518008;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=rs397518008" 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=rs397518008" 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=RCV000002446 OR RCV000671576 OR RCV000824792 OR RCV001851582 OR RCV003450613" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002446, RCV000671576, RCV000824792, RCV001851582, RCV003450613" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002446...</a>
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<p>In patients with Usher syndrome type IIa (USH2A; <a href="/entry/276901">276901</a>), <a href="#12" class="mim-tip-reference" title="Eudy, J. D., Weston, M. D., Yao, S., Hoover, D. M., Rehm, H. L., Ma-Edmonds, M., Yan, D., Ahmad, I., Cheng, J. J., Ayuso, C., Cremers, C., Davenport, S., Moller, C., Talmadge, C. B., Beisel, K. W., Tamayo, M., Morton, C. C., Swaroop, A., Kimberling, W. J., Sumegi, J. <strong>Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa.</strong> Science 280: 1753-1757, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9624053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9624053</a>] [<a href="https://doi.org/10.1126/science.280.5370.1753" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9624053">Eudy et al. (1998)</a> found a 1-bp deletion, reported by them as 2913delG, in the USH2A gene. This mutation is correctly referred to as 2898delG (T967FS) (<a href="#29" class="mim-tip-reference" title="Weston, M. D., Eudy, J. D., Fujita, S., Yao, S.-F., Usami, S., Cremers, C., Greenburg, J., Ramesar, R., Martini, A., Moller, C., Smith, R. J., Sumegi, J., Kimberling, W. J. <strong>Genomic structure and identification of novel mutations in usherin, the gene responsible for Usher syndrome type IIa.</strong> Am. J. Hum. Genet. 66: 1199-1210, 2000. Note: Erratum: Am. J. Hum. Genet. 66: 2020 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10729113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10729113</a>] [<a href="https://doi.org/10.1086/302855" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10729113">Weston et al., 2000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10729113+9624053" 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> rs111033367 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033367;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/rs111033367?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=rs111033367" 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=rs111033367" 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=RCV000002447 OR RCV000310917 OR RCV000710335 OR RCV000793722 OR RCV000984013 OR RCV001073308 OR RCV002482816" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002447, RCV000310917, RCV000710335, RCV000793722, RCV000984013, RCV001073308, RCV002482816" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002447...</a>
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<p>In the Louisiana Acadian population with Usher syndrome type IIa (USH2A; <a href="/entry/276901">276901</a>), <a href="#12" class="mim-tip-reference" title="Eudy, J. D., Weston, M. D., Yao, S., Hoover, D. M., Rehm, H. L., Ma-Edmonds, M., Yan, D., Ahmad, I., Cheng, J. J., Ayuso, C., Cremers, C., Davenport, S., Moller, C., Talmadge, C. B., Beisel, K. W., Tamayo, M., Morton, C. C., Swaroop, A., Kimberling, W. J., Sumegi, J. <strong>Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa.</strong> Science 280: 1753-1757, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9624053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9624053</a>] [<a href="https://doi.org/10.1126/science.280.5370.1753" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9624053">Eudy et al. (1998)</a> found heterozygosity for a dinucleotide deletion that they reported as 4353-4delCT. This mutation is correctly referred to as 4338-9delCT (C1447FS) (<a href="#29" class="mim-tip-reference" title="Weston, M. D., Eudy, J. D., Fujita, S., Yao, S.-F., Usami, S., Cremers, C., Greenburg, J., Ramesar, R., Martini, A., Moller, C., Smith, R. J., Sumegi, J., Kimberling, W. J. <strong>Genomic structure and identification of novel mutations in usherin, the gene responsible for Usher syndrome type IIa.</strong> Am. J. Hum. Genet. 66: 1199-1210, 2000. Note: Erratum: Am. J. Hum. Genet. 66: 2020 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10729113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10729113</a>] [<a href="https://doi.org/10.1086/302855" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10729113">Weston et al., 2000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10729113+9624053" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Ebermann, I., Koenekoop, R. K., Lopez, I., Bou-Khzam, L., Pigeon, R., Bolz, H. J. <strong>An USH2A founder mutation is the major cause of Usher syndrome type 2 in Canadians of French origin and confirms common roots of Quebecois and Acadians.</strong> Europ. J. Hum. Genet. 17: 80-84, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18665195/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18665195</a>] [<a href="https://doi.org/10.1038/ejhg.2008.143" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18665195">Ebermann et al. (2009)</a> identified the homozygous 4338delCT mutation in 4 of 9 French Canadian families with Usher syndrome type IIa from Quebec and New Brunswick, the former Acadia. Affected individuals from 2 additional families carried the mutation in heterozygosity. Altogether, the 4338delCT mutation accounted for 10 (55.6%) of 18 disease alleles. Haplotype analysis indicated a founder effect. The findings indicated that the Acadian and Quebec populations share common ancestors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18665195" 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="Ebermann, I., Phillips, J. B., Liebau, M. C., Koenekoop, R. K., Schermer, B., Lopez, I., Schafer, E., Roux, A.-F., Dafinger, C., Bernd, A., Zrenner, E., Claustres, M., Blanco, B., Nurnberg, G., Nurnberg, P., Ruland, R., Westerfield, M., Benzing, T., Bolz, H. J. <strong>PDZD7 is a modifier of retinal disease and a contributor to digenic Usher syndrome.</strong> J. Clin. Invest. 120: 1812-1823, 2010. Note: Erratum: J. Clin. Invest. 121: 821 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20440071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20440071</a>] [<a href="https://doi.org/10.1172/JCI39715" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20440071">Ebermann et al. (2010)</a> studied 2 French Canadian sisters with USH2A who were homozygous for the 4338delCT mutation in the USH2A gene, and identified an additional de novo heterozygous frameshift mutation in the PDZD7 gene (<a href="/entry/612971#0001">612971.0001</a>) in 1 of the sisters, who had earlier-onset and more severe retinal disease. The PDZD7 mutation was not present in the other sister, who had a much milder retinal phenotype. <a href="#11" class="mim-tip-reference" title="Ebermann, I., Phillips, J. B., Liebau, M. C., Koenekoop, R. K., Schermer, B., Lopez, I., Schafer, E., Roux, A.-F., Dafinger, C., Bernd, A., Zrenner, E., Claustres, M., Blanco, B., Nurnberg, G., Nurnberg, P., Ruland, R., Westerfield, M., Benzing, T., Bolz, H. J. <strong>PDZD7 is a modifier of retinal disease and a contributor to digenic Usher syndrome.</strong> J. Clin. Invest. 120: 1812-1823, 2010. Note: Erratum: J. Clin. Invest. 121: 821 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20440071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20440071</a>] [<a href="https://doi.org/10.1172/JCI39715" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20440071">Ebermann et al. (2010)</a> concluded that PDZD7 is a retinal disease modifier in patients with USH2A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20440071" 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 members of a Swedish family with type IIa Usher syndrome (USH2A; <a href="/entry/276901">276901</a>), <a href="#29" class="mim-tip-reference" title="Weston, M. D., Eudy, J. D., Fujita, S., Yao, S.-F., Usami, S., Cremers, C., Greenburg, J., Ramesar, R., Martini, A., Moller, C., Smith, R. J., Sumegi, J., Kimberling, W. J. <strong>Genomic structure and identification of novel mutations in usherin, the gene responsible for Usher syndrome type IIa.</strong> Am. J. Hum. Genet. 66: 1199-1210, 2000. Note: Erratum: Am. J. Hum. Genet. 66: 2020 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10729113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10729113</a>] [<a href="https://doi.org/10.1086/302855" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10729113">Weston et al. (2000)</a> identified a 779T-G transversion in the USH2A gene, resulting in a leu260-to-ter (L260X) change. The mutation was present in compound heterozygous state with the 2299delG mutation (<a href="#0001">608400.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10729113" 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="#29" class="mim-tip-reference" title="Weston, M. D., Eudy, J. D., Fujita, S., Yao, S.-F., Usami, S., Cremers, C., Greenburg, J., Ramesar, R., Martini, A., Moller, C., Smith, R. J., Sumegi, J., Kimberling, W. J. <strong>Genomic structure and identification of novel mutations in usherin, the gene responsible for Usher syndrome type IIa.</strong> Am. J. Hum. Genet. 66: 1199-1210, 2000. Note: Erratum: Am. J. Hum. Genet. 66: 2020 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10729113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10729113</a>] [<a href="https://doi.org/10.1086/302855" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10729113">Weston et al. (2000)</a> found homozygosity for a cys319-to-tyr (C319Y) mutation in the USH2A gene in a proband with Usher syndrome type IIa (USH2A; <a href="/entry/276901">276901</a>) from a Hispanic American family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10729113" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002450 OR RCV000032523 OR RCV000174625 OR RCV000239000 OR RCV000404009 OR RCV000504814 OR RCV000505146 OR RCV000623925 OR RCV001257905 OR RCV001535506 OR RCV001813938 OR RCV002251859" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002450, RCV000032523, RCV000174625, RCV000239000, RCV000404009, RCV000504814, RCV000505146, RCV000623925, RCV001257905, RCV001535506, RCV001813938, RCV002251859" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002450...</a>
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<p><a href="#25" class="mim-tip-reference" title="Rivolta, C., Sweklo, E. A., Berson, E. L., Dryja, T. P. <strong>Missense mutation in the USH2A gene: association with recessive retinitis pigmentosa without hearing loss.</strong> Am. J. Hum. Genet. 66: 1975-1978, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10775529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10775529</a>] [<a href="https://doi.org/10.1086/302926" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10775529">Rivolta et al. (2000)</a> described a cys759-to-phe (C759F) missense mutation caused by a G-T change in the USH2A gene that was associated with autosomal recessive retinitis pigmentosa without hearing loss (RP39; <a href="/entry/613809">613809</a>). The amino acid at this position is within the fifth laminin-epidermal growth factor-like domain and participates in a presumed disulfide bridge. The mutation was found in 4.5% of 224 patients with recessive RP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10775529" 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="Rivolta, C., Berson, E. L., Dryja, T. P. <strong>Paternal uniparental heterodisomy with partial isodisomy of chromosome 1 in a patient with retinitis pigmentosa without hearing loss and a missense mutation in the Usher syndrome type II gene USH2A.</strong> Arch. Ophthal. 120: 1566-1571, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12427073/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12427073</a>] [<a href="https://doi.org/10.1001/archopht.120.11.1566" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12427073">Rivolta et al. (2002)</a> reported a patient with RP without hearing loss caused by a homozygous C759F mutation in the USH2A gene. Her father was heterozygous for this change, and her mother was a noncarrier. Further evaluation with microsatellite markers revealed that the patient had inherited 2 copies of chromosome 1 from her father and none from her mother. The 2 paternally derived copies of chromosome 1 were heteroallelic from the centromere to the proximal short and long arms. The distal regions of the short and long arms of chromosome 1 were homoallelic, including the region of 1q with the mutant USH2A allele. This genetic pattern is compatible with uniparental primary heterodisomy with regions of homozygosity arising through a nondisjunction event during paternal meiosis I and subsequent trisomy rescue or gamete complementation. A paternal second cousin of the patient also had RP and had an identical heterozygous mutation in the USH2A gene in the same codon. However, the analysis of an isocoding polymorphism 20 bp away and closely linked microsatellite markers in the patient and family members indicated that the 2 mutant alleles were unlikely to be identical by descent and that the 2 relatives fortuitously had RP and a mutation in the same codon of the USH2A gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12427073" 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="#22" class="mim-tip-reference" title="Pozo, M. G., Bravo-Gil, N., Mendez-Vidal, C., Montero-de-Espinosa, I., Millan, J. M., Dopazo, J., Borrego, S., Antinolo, G. <strong>Re-evaluation casts doubt on the pathogenicity of homozygous USH2A p.C759F.</strong> Am. J. Med. Genet. 167A: 1597-1600, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25823529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25823529</a>] [<a href="https://doi.org/10.1002/ajmg.a.37003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25823529">Pozo et al. (2015)</a> noted that 15 families with RP had been reported to have a homozygous C759F variant (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338902;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs80338902</a>) in the USH2A gene. In all reviewed cases, the segregation data either were not shown or were inconclusive. <a href="#22" class="mim-tip-reference" title="Pozo, M. G., Bravo-Gil, N., Mendez-Vidal, C., Montero-de-Espinosa, I., Millan, J. M., Dopazo, J., Borrego, S., Antinolo, G. <strong>Re-evaluation casts doubt on the pathogenicity of homozygous USH2A p.C759F.</strong> Am. J. Med. Genet. 167A: 1597-1600, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25823529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25823529</a>] [<a href="https://doi.org/10.1002/ajmg.a.37003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25823529">Pozo et al. (2015)</a> restudied a Spanish family (S23) in which <a href="#5" class="mim-tip-reference" title="Bernal, S., Ayuso, C., Antinolo, G., Gimenez, A., Borrego, S., Trujillo, M. J., Marcos, I., Calaf, M., Del Rio, E., Baiget, M. <strong>Mutations in USH2A in Spanish patients with autosomal recessive retinitis pigmentosa: high prevalence and phenotypic variation.</strong> J. Med. Genet. 40: e8, 2003. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12525556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12525556</a>] [<a href="https://doi.org/10.1136/jmg.40.1.e8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12525556">Bernal et al. (2003)</a> had identified homozygosity for C759F in 2 affected and 2 unaffected sibs. By next-generation sequencing, they identified homozygosity for an R560C mutation in the PDE6B gene (<a href="/entry/180072#0008">180072.0008</a>) that segregated with the disorder in the family and was absent in 200 control individuals. <a href="#22" class="mim-tip-reference" title="Pozo, M. G., Bravo-Gil, N., Mendez-Vidal, C., Montero-de-Espinosa, I., Millan, J. M., Dopazo, J., Borrego, S., Antinolo, G. <strong>Re-evaluation casts doubt on the pathogenicity of homozygous USH2A p.C759F.</strong> Am. J. Med. Genet. 167A: 1597-1600, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25823529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25823529</a>] [<a href="https://doi.org/10.1002/ajmg.a.37003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25823529">Pozo et al. (2015)</a> suggested that the C759F variant might not be pathogenic and proposed genetic reevaluation of other reported families with the C759F variant. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25823529+12525556" 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 discovery cohort of 186 unrelated probands with autosomal recessive retinal degeneration without childhood hearing loss, <a href="#16" class="mim-tip-reference" title="Lenassi, E., Vincent, A., Li, Z., Saihan, Z., Coffey, A. J., Steele-Stallard, H. B., Moore, A. T., Steel, K. P., Luxon, L. M., Heon, E., Bitner-Glindzicz, M., Webster, A. R. <strong>A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants.</strong> Europ. J. Hum. Genet. 23: 1318-1327, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25649381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25649381</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25649381[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2014.283" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25649381">Lenassi et al. (2015)</a> found the c.2276G-T transversion in USH2A gene, resulting in a C759F substitution, in 11 alleles (once in homozygosity). In the replication cohort of 84 unrelated probands with autosomal recessive retinal degeneration, the allele was found 5 times, once in homozygosity; and in a third panel of 187 patients with nonsyndromic adult-onset autosomal recessive retinitis pigmentosa, it was found 5 times, once in homozygosity. <a href="#16" class="mim-tip-reference" title="Lenassi, E., Vincent, A., Li, Z., Saihan, Z., Coffey, A. J., Steele-Stallard, H. B., Moore, A. T., Steel, K. P., Luxon, L. M., Heon, E., Bitner-Glindzicz, M., Webster, A. R. <strong>A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants.</strong> Europ. J. Hum. Genet. 23: 1318-1327, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25649381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25649381</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25649381[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2014.283" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25649381">Lenassi et al. (2015)</a> noted that the C759F mutation is often considered to be the most common disease-causing variant in patients with nonsyndromic retinitis pigmentosa. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25649381" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To assess the role of the C759F mutation in autosomal recessive retinitis pigmentosa and Usher syndrome type 2, <a href="#21" class="mim-tip-reference" title="Perez-Carro, R., Blanco-Kelly, F., Galbis-Martinez, L., Garcia-Garcia, G., Aller, E., Garcia-Sandoval, B., Minguez, P., Corton, M., Mahillo-Fernandez, I., Martin-Merida, I., Avila-Fernandez, A., Millan, J. M., Ayuso, C. <strong>Unravelling the pathogenic role and genotype-phenotype correlation of the USH2A p.(cys759phe) variant among Spanish families.</strong> PLoS One 13: e0199048, 2018. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29912909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29912909</a>] [<a href="https://doi.org/10.1371/journal.pone.0199048" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29912909">Perez-Carro et al. (2018)</a> performed a comprehensive genetic and clinical study of 57 families with affected members who carried the C759F mutation on at least 1 allele. Of the 57 probands, 11 were homozygous for the mutation, 42 were compound heterozygous with another mutation in the USH2A gene, and the remaining 4 also carried mutations in RP1 (<a href="/entry/603937">603937</a>), PROM1 (<a href="/entry/604365">604365</a>), or CNGB1 (<a href="/entry/600724">600724</a>). The 2 patients with PROM1 and CNGB1 mutations, and 1 patient with mutated RP1, were homozygous for those mutations in addition to the C759F mutation in USH2A; the second patient with mutation in RP1 was heterozygous for that mutation. The authors noted that although the C759F variant is enriched in the Spanish population, no homozygous individuals had been identified in control populations, even in Spanish population databases. <a href="#21" class="mim-tip-reference" title="Perez-Carro, R., Blanco-Kelly, F., Galbis-Martinez, L., Garcia-Garcia, G., Aller, E., Garcia-Sandoval, B., Minguez, P., Corton, M., Mahillo-Fernandez, I., Martin-Merida, I., Avila-Fernandez, A., Millan, J. M., Ayuso, C. <strong>Unravelling the pathogenic role and genotype-phenotype correlation of the USH2A p.(cys759phe) variant among Spanish families.</strong> PLoS One 13: e0199048, 2018. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29912909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29912909</a>] [<a href="https://doi.org/10.1371/journal.pone.0199048" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29912909">Perez-Carro et al. (2018)</a> stated that the C759F mutation alters a highly conserved residue in a domain that enhances USH2A stability in the basement membrane by prompting its interaction with collagen IV (see <a href="/entry/120070">120070</a>). The mutation was also predicted to disrupt a disulfide bridge, leading to erroneous protein folding and instability. While <a href="#22" class="mim-tip-reference" title="Pozo, M. G., Bravo-Gil, N., Mendez-Vidal, C., Montero-de-Espinosa, I., Millan, J. M., Dopazo, J., Borrego, S., Antinolo, G. <strong>Re-evaluation casts doubt on the pathogenicity of homozygous USH2A p.C759F.</strong> Am. J. Med. Genet. 167A: 1597-1600, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25823529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25823529</a>] [<a href="https://doi.org/10.1002/ajmg.a.37003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25823529">Pozo et al. (2015)</a> had questioned the pathogenicity of the C759F variant, at least in homozygosity, <a href="#21" class="mim-tip-reference" title="Perez-Carro, R., Blanco-Kelly, F., Galbis-Martinez, L., Garcia-Garcia, G., Aller, E., Garcia-Sandoval, B., Minguez, P., Corton, M., Mahillo-Fernandez, I., Martin-Merida, I., Avila-Fernandez, A., Millan, J. M., Ayuso, C. <strong>Unravelling the pathogenic role and genotype-phenotype correlation of the USH2A p.(cys759phe) variant among Spanish families.</strong> PLoS One 13: e0199048, 2018. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29912909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29912909</a>] [<a href="https://doi.org/10.1371/journal.pone.0199048" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29912909">Perez-Carro et al. (2018)</a> pointed out that no other candidate variants in the USH2A or any other RP genes that could explain the phenotypes were found in their patients by next-generation sequencing. They concluded that C759F homozygosity is associated with a later diagnosis of RP and slower progression of visual field loss, with a very late hypoacusis diagnosis (around the seventh decade). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=29912909+25823529" 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> rs111033364 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033364;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/rs111033364?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=rs111033364" 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=rs111033364" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 patients with Usher syndrome type IIa (USH2A; <a href="/entry/276901">276901</a>), <a href="#28" class="mim-tip-reference" title="van Wijk, E., Pennings, R. J. E., te Brinke, H., Claassen, A., Yntema, H. G., Hoefsloot, L. H., Cremers, F. P. M., Cremers, C. W. R. J., Kremer, H. <strong>Identification of 51 novel exons of the Usher syndrome type 2A (USH2A) gene that encode multiple conserved functional domains and that are mutated in patients with Usher syndrome type II.</strong> Am. J. Hum. Genet. 74: 738-744, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15015129/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15015129</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15015129[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/383096" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15015129">van Wijk et al. (2004)</a> found compound heterozygosity for a trp3955-to-ter (W3955X) mutation in the USH2A gene and 2 different mutations: a 949C-A transversion in one patient, resulting in an arg317-to-arg mutation (R317R; <a href="#0008">608400.0008</a>), which was predicted to create an additional 5-prime splice site in exon 5; and a 1256G-T transversion, resulting in a cys419-to-phe substitution (C419F; <a href="#0009">608400.0009</a>) in the second patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15015129" 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 arg317-to-arg (R317R) mutation in the USH2A gene that was found in compound heterozygous state in patients with Usher syndrome type IIa (USH2A; <a href="/entry/276901">276901</a>) by <a href="#28" class="mim-tip-reference" title="van Wijk, E., Pennings, R. J. E., te Brinke, H., Claassen, A., Yntema, H. G., Hoefsloot, L. H., Cremers, F. P. M., Cremers, C. W. R. J., Kremer, H. <strong>Identification of 51 novel exons of the Usher syndrome type 2A (USH2A) gene that encode multiple conserved functional domains and that are mutated in patients with Usher syndrome type II.</strong> Am. J. Hum. Genet. 74: 738-744, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15015129/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15015129</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15015129[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/383096" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15015129">van Wijk et al. (2004)</a>, see <a href="#0007">608400.0007</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15015129" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 USHER SYNDROME, TYPE IIA</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121912600 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912600;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/rs121912600?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=rs121912600" 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=rs121912600" 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=RCV000002453 OR RCV000224697 OR RCV000504809 OR RCV000778222 OR RCV000824795 OR RCV000984315 OR RCV001074823 OR RCV002482817" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002453, RCV000224697, RCV000504809, RCV000778222, RCV000824795, RCV000984315, RCV001074823, RCV002482817" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002453...</a>
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<p>For discussion of the cys419-to-phe (C419F) mutation in the USH2A gene that was found in compound heterozygous state in patients with Usher syndrome type IIa (USH2A; <a href="/entry/276901">276901</a>) by <a href="#28" class="mim-tip-reference" title="van Wijk, E., Pennings, R. J. E., te Brinke, H., Claassen, A., Yntema, H. G., Hoefsloot, L. H., Cremers, F. P. M., Cremers, C. W. R. J., Kremer, H. <strong>Identification of 51 novel exons of the Usher syndrome type 2A (USH2A) gene that encode multiple conserved functional domains and that are mutated in patients with Usher syndrome type II.</strong> Am. J. Hum. Genet. 74: 738-744, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15015129/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15015129</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15015129[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/383096" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15015129">van Wijk et al. (2004)</a>, see <a href="#0007">608400.0007</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15015129" 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>.0010 USHER SYNDROME, TYPE IIA</strong>
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RETINITIS PIGMENTOSA 39, INCLUDED
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USH2A, 4-BP INS, NT239
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776538 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776538;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=rs587776538" 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=rs587776538" 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=RCV000002454 OR RCV000002455" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002454, RCV000002455" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002454...</a>
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<p>In a consanguineous family of Iraqi Jewish origin in which some members had Usher syndrome type IIa (USH2A; <a href="/entry/276901">276901</a>) and others had nonsyndromic retinitis pigmentosa (RP39; <a href="/entry/613809">613809</a>), <a href="#15" class="mim-tip-reference" title="Kaiserman, N., Obolensky, A., Banin, E., Sharon, D. <strong>Novel USH2A mutations in Israeli patients with retinitis pigmentosa and Usher syndrome type 2.</strong> Arch. Ophthal. 125: 219-224, 2007. Note: Erratum: Arch. Ophthal. 125: 1013, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17296898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17296898</a>] [<a href="https://doi.org/10.1001/archopht.125.2.219" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17296898">Kaiserman et al. (2007)</a> identified compound heterozygosity for 2 null mutations in the USH2A gene in those affected with USH2A: a 4-bp insertion (239_242insCGAT) resulting in a frameshift at position 80 (Thr80fs), and a 2209C-T transition resulting in an arg737-to-ter (R737X; <a href="#0011">608400.0011</a>) substitution. In those affected with nonsyndromic RP, they identified compound heterozygosity for one of the null mutations and a 14021A-G transition resulting in an arg4674-to-gly substitution (R4674G; <a href="#0012">608400.0012</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17296898" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0011 USHER SYNDROME, TYPE IIA</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs111033334 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033334;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/rs111033334?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=rs111033334" 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=rs111033334" 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=RCV000002456 OR RCV000002457 OR RCV000725261 OR RCV000824794 OR RCV001003279" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002456, RCV000002457, RCV000725261, RCV000824794, RCV001003279" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002456...</a>
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<p>For discussion of the arg737-to-ter (R737X) mutation in the USH2A gene that was found in compound heterozygous state in a family in which some members had Usher syndrome type IIa (USH2A; <a href="/entry/276901">276901</a>) and others had nonsyndromic retinitis pigmentosa (RP39; <a href="/entry/613809">613809</a>) by <a href="#15" class="mim-tip-reference" title="Kaiserman, N., Obolensky, A., Banin, E., Sharon, D. <strong>Novel USH2A mutations in Israeli patients with retinitis pigmentosa and Usher syndrome type 2.</strong> Arch. Ophthal. 125: 219-224, 2007. Note: Erratum: Arch. Ophthal. 125: 1013, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17296898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17296898</a>] [<a href="https://doi.org/10.1001/archopht.125.2.219" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17296898">Kaiserman et al. (2007)</a>, see <a href="#0010">608400.0010</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17296898" 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>.0012 RETINITIS PIGMENTOSA 39</strong>
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USH2A, ARG4674GLY
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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> rs80338904 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338904;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/rs80338904?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=rs80338904" 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=rs80338904" 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=RCV000002458 OR RCV000032522 OR RCV001379272" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002458, RCV000032522, RCV001379272" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002458...</a>
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<p>For discussion of the arg4674-to-gly (R4674G) mutation in the USH2A gene that was found in compound heterozygous state in a family in which some members had Usher syndrome type IIa (USH2A; <a href="/entry/276901">276901</a>) and others had nonsyndromic retinitis pigmentosa (RP39; <a href="/entry/613809">613809</a>) by <a href="#15" class="mim-tip-reference" title="Kaiserman, N., Obolensky, A., Banin, E., Sharon, D. <strong>Novel USH2A mutations in Israeli patients with retinitis pigmentosa and Usher syndrome type 2.</strong> Arch. Ophthal. 125: 219-224, 2007. Note: Erratum: Arch. Ophthal. 125: 1013, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17296898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17296898</a>] [<a href="https://doi.org/10.1001/archopht.125.2.219" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17296898">Kaiserman et al. (2007)</a>, see <a href="#0010">608400.0010</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17296898" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0013" class="mim-anchor"></a>
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<h4>
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<strong>.0013 USHER SYNDROME, TYPE IIA</strong>
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USH2A, IVS40AS, A-G, -2144
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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> rs786200928 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786200928;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/rs786200928?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=rs786200928" 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=rs786200928" 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=RCV000023700 OR RCV000505092 OR RCV000664608 OR RCV000787740 OR RCV000814767 OR RCV001003267 OR RCV001074209 OR RCV001376510 OR RCV001824575 OR RCV004017262" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023700, RCV000505092, RCV000664608, RCV000787740, RCV000814767, RCV001003267, RCV001074209, RCV001376510, RCV001824575, RCV004017262" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023700...</a>
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<p>In a French patient with Usher syndrome type IIa (USH2A; <a href="/entry/276901">276901</a>), <a href="#26" class="mim-tip-reference" title="Vache, C., Besnard, T., le Berre, P., Garcia-Garcia, G., Baux, D., Larrieu, L., Abadie, C., Blanchet, C., Bolz, H. J., Millan, J., Hamel, C., Malcolm, S., Claustres, M., Roux, A.-F. <strong>Usher syndrome type 2 caused by activation of an USH2A pseudoexon: implications for diagnosis and therapy.</strong> Hum. Mutat. 33: 104-108, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22009552/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22009552</a>] [<a href="https://doi.org/10.1002/humu.21634" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22009552">Vache et al. (2012)</a> identified compound heterozygosity for 2 mutations in the USH2A gene: a heterozygous A-to-G transition deep within intron 40 (c.7595-2144) and a 1-bp duplication (3129dupT; <a href="#0014">608400.0014</a>), resulting in a frameshift. Two other individuals in a different branch of the family had the intron 41 mutation and a different heterozygous frameshift mutation, 8890dupT (<a href="#0015">608400.0015</a>). The intron 41 mutation was found only after RT-PCR amplification of RNA from nasal cells in 1 patient showed an aberrant USH2A out-of-frame transcript predicted to result in a truncated protein that would not be anchored to the cell membrane. DNA studies showed that the A-to-G transition resulted in activation of a pseudoexon between exons 40 and 41, causing a 153-bp insertion and a frameshift. The nomenclature used for this insertion was r.7594_7595ins7595-2296_7595-2143. This mutation was not found in 338 alleles. However, this mutation was found in 4 of 20 USH2A patients with no identified mutation or only a single pathogenic mutation, as well as in 4 of 18 Spanish patients with incomplete USH2A genotypes. <a href="#26" class="mim-tip-reference" title="Vache, C., Besnard, T., le Berre, P., Garcia-Garcia, G., Baux, D., Larrieu, L., Abadie, C., Blanchet, C., Bolz, H. J., Millan, J., Hamel, C., Malcolm, S., Claustres, M., Roux, A.-F. <strong>Usher syndrome type 2 caused by activation of an USH2A pseudoexon: implications for diagnosis and therapy.</strong> Hum. Mutat. 33: 104-108, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22009552/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22009552</a>] [<a href="https://doi.org/10.1002/humu.21634" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22009552">Vache et al. (2012)</a> noted that the identification of a deep intronic mutation in a pseudoexon raised the possibility of a new therapeutic strategy using antisense oligonucleotide chemistry to restore normal splicing via exon skipping. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22009552" 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> rs786205115 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786205115;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/rs786205115?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=rs786205115" 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=rs786205115" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the 1-bp duplication in the USH2A gene (3129dupT) that was found in compound heterozygous state in a patient with Usher syndrome type IIa (USH2A; <a href="/entry/276901">276901</a>) by <a href="#26" class="mim-tip-reference" title="Vache, C., Besnard, T., le Berre, P., Garcia-Garcia, G., Baux, D., Larrieu, L., Abadie, C., Blanchet, C., Bolz, H. J., Millan, J., Hamel, C., Malcolm, S., Claustres, M., Roux, A.-F. <strong>Usher syndrome type 2 caused by activation of an USH2A pseudoexon: implications for diagnosis and therapy.</strong> Hum. Mutat. 33: 104-108, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22009552/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22009552</a>] [<a href="https://doi.org/10.1002/humu.21634" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22009552">Vache et al. (2012)</a>, see <a href="#0013">608400.0013</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22009552" 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> rs786205116 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786205116;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/rs786205116?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=rs786205116" 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=rs786205116" 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=RCV000023702 OR RCV002513202" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023702, RCV002513202" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023702...</a>
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<p>For discussion of the 1-bp duplication in the USH2A gene (8890dupT) that was found in compound heterozygous state in patients with Usher syndrome type IIa (USH2A; <a href="/entry/276901">276901</a>) by <a href="#26" class="mim-tip-reference" title="Vache, C., Besnard, T., le Berre, P., Garcia-Garcia, G., Baux, D., Larrieu, L., Abadie, C., Blanchet, C., Bolz, H. J., Millan, J., Hamel, C., Malcolm, S., Claustres, M., Roux, A.-F. <strong>Usher syndrome type 2 caused by activation of an USH2A pseudoexon: implications for diagnosis and therapy.</strong> Hum. Mutat. 33: 104-108, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22009552/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22009552</a>] [<a href="https://doi.org/10.1002/humu.21634" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22009552">Vache et al. (2012)</a>, see <a href="#0013">608400.0013</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22009552" 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> rs201527662 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs201527662;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/rs201527662?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=rs201527662" 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=rs201527662" 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=RCV000132710 OR RCV000576637 OR RCV000595137 OR RCV000986542 OR RCV001003277 OR RCV001074347 OR RCV002469023 OR RCV004796037" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000132710, RCV000576637, RCV000595137, RCV000986542, RCV001003277, RCV001074347, RCV002469023, RCV004796037" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000132710...</a>
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<p>In 5 Korean probands with retinitis pigmentosa (RP39; <a href="/entry/613809">613809</a>), <a href="#14" class="mim-tip-reference" title="Jung, S., Park, Y. C., Lee, D., Kim, S., Kim, S.-M., Kim, Y., Lee, D., Hyun, J., Koh, I., Lee, J.-Y. <strong>Exome sequencing identified five novel USH2A variants in Korean patients with retinitis pigmentosa.</strong> Ophthalmic Genet. 44: 163-170, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36314366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36314366</a>] [<a href="https://doi.org/10.1080/13816810.2022.2138456" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36314366">Jung et al. (2023)</a> identified compound heterozygosity for a c.2802T-G transversion in exon 13 of the USH2A gene, resulting in a cys934-to-trp (C934W) substitution within the LamE 8 domain, and another missense or truncating mutation in the USH2A gene (e.g., <a href="#0017">608400.0017</a> and <a href="#0018">608400.0018</a>). Hearing tests were not performed, but no hearing problems were reported by any of the probands. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36314366" 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> rs768161313 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs768161313;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/rs768161313?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=rs768161313" 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=rs768161313" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 Korean probands with retinitis pigmentosa (RP39; <a href="/entry/613809">613809</a>), <a href="#14" class="mim-tip-reference" title="Jung, S., Park, Y. C., Lee, D., Kim, S., Kim, S.-M., Kim, Y., Lee, D., Hyun, J., Koh, I., Lee, J.-Y. <strong>Exome sequencing identified five novel USH2A variants in Korean patients with retinitis pigmentosa.</strong> Ophthalmic Genet. 44: 163-170, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36314366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36314366</a>] [<a href="https://doi.org/10.1080/13816810.2022.2138456" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36314366">Jung et al. (2023)</a> identified compound heterozygosity for a 4-bp deletion (c.13112_13115delAAAT) in exon 63 of the USH2A gene, causing a frameshift predicted to result in a premature termination codon (Gln4371fs), and another missense or truncating mutation in the USH2A gene (e.g., <a href="#0016">608400.0016</a>). Hearing tests were not performed, but no hearing problems were reported by the probands. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36314366" 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> rs201529124 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs201529124;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/rs201529124?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=rs201529124" 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=rs201529124" 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=RCV001067861 OR RCV001376322 OR RCV002282450 OR RCV003455294 OR RCV004813699 OR RCV005021413" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001067861, RCV001376322, RCV002282450, RCV003455294, RCV004813699, RCV005021413" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001067861...</a>
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<p>In 2 Korean probands with retinitis pigmentosa (RP39; <a href="/entry/613809">613809</a>), <a href="#14" class="mim-tip-reference" title="Jung, S., Park, Y. C., Lee, D., Kim, S., Kim, S.-M., Kim, Y., Lee, D., Hyun, J., Koh, I., Lee, J.-Y. <strong>Exome sequencing identified five novel USH2A variants in Korean patients with retinitis pigmentosa.</strong> Ophthalmic Genet. 44: 163-170, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36314366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36314366</a>] [<a href="https://doi.org/10.1080/13816810.2022.2138456" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36314366">Jung et al. (2023)</a> identified compound heterozygosity for a c.4732C-T transition in exon 22 of the USH2A gene, resulting in an arg1578-to-cys (R1578C) substitution within the LamG 1 domain, and another missense or truncating mutation in the USH2A gene (e.g., <a href="#0016">608400.0016</a>). Hearing tests were not performed, but no hearing problems were reported by the probands. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36314366" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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[<a href="https://doi.org/10.1093/hmg/ddi416" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.2006.041764" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/sj.ejhg.5201138" target="_blank">Full Text</a>]
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<strong>Molecular and in silico analyses of the full-length isoform of usherin identify new pathogenic alleles in Usher type II patients.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17405132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17405132</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17405132" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.20513" target="_blank">Full Text</a>]
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Bernal, S., Ayuso, C., Antinolo, G., Gimenez, A., Borrego, S., Trujillo, M. J., Marcos, I., Calaf, M., Del Rio, E., Baiget, M.
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<strong>Mutations in USH2A in Spanish patients with autosomal recessive retinitis pigmentosa: high prevalence and phenotypic variation.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12525556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12525556</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12525556" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmg.40.1.e8" target="_blank">Full Text</a>]
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Bernal, S., Meda, C., Solans, T., Ayuso, C., Garcia-Sandoval, B., Valverde, D., Del Rio, E., Baiget, M.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16098008/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16098008</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16098008" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2005.00481.x" target="_blank">Full Text</a>]
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Dreyer, B., Brox, V., Tranebjaerg, L., Rosenberg, T., Sadeghi, A. M., Moller, C., Nilssen, O.
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<strong>Spectrum of USH2A mutations in Scandinavian patients with Usher syndrome type II.</strong>
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Hum. Mutat. 29: 451 only, 2008. Note: Full article online.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18273898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18273898</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18273898" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.9524" target="_blank">Full Text</a>]
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Dreyer, B., Tranebjaerg, L., Brox, V., Rosenberg, T., Moller, C., Beneyto, M., Weston, M. D., Kimberling, W. J., Nilssen, O.
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[<a href="https://doi.org/10.1086/321269" target="_blank">Full Text</a>]
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Dreyer, B., Tranebjaerg, L., Rosenberg, T., Weston, M. D., Kimberling, W. J., Nilssen, O.
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[<a href="https://doi.org/10.1038/sj.ejhg.5200491" target="_blank">Full Text</a>]
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<a id="Ebermann2009" class="mim-anchor"></a>
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<strong>An USH2A founder mutation is the major cause of Usher syndrome type 2 in Canadians of French origin and confirms common roots of Quebecois and Acadians.</strong>
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[<a href="https://doi.org/10.1038/ejhg.2008.143" target="_blank">Full Text</a>]
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Ebermann, I., Phillips, J. B., Liebau, M. C., Koenekoop, R. K., Schermer, B., Lopez, I., Schafer, E., Roux, A.-F., Dafinger, C., Bernd, A., Zrenner, E., Claustres, M., Blanco, B., Nurnberg, G., Nurnberg, P., Ruland, R., Westerfield, M., Benzing, T., Bolz, H. J.
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[<a href="https://doi.org/10.1172/JCI39715" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1126/science.280.5370.1753" target="_blank">Full Text</a>]
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<strong>Identification of the mouse and rat orthologs of the gene mutated in Usher syndrome type IIA and the cellular source of USH2A mRNA in retina, a target tissue of the disease.</strong>
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[<a href="https://doi.org/10.1006/geno.2002.6823" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1080/13816810.2022.2138456" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1001/archopht.125.2.219" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/ejhg.2014.283" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.0610950104" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1086/302332" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.2009.075143" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1046/j.1399-0004.2004.00216.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1371/journal.pone.0199048" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.37003" target="_blank">Full Text</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/10.1001/archopht.120.11.1566" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1086/302926" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/humu.21634" target="_blank">Full Text</a>]
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<a id="Weston2000" class="mim-anchor"></a>
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Weston, M. D., Eudy, J. D., Fujita, S., Yao, S.-F., Usami, S., Cremers, C., Greenburg, J., Ramesar, R., Martini, A., Moller, C., Smith, R. J., Sumegi, J., Kimberling, W. J.
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<strong>Genomic structure and identification of novel mutations in usherin, the gene responsible for Usher syndrome type IIa.</strong>
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Am. J. Hum. Genet. 66: 1199-1210, 2000. Note: Erratum: Am. J. Hum. Genet. 66: 2020 only, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10729113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10729113</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10729113" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/302855" target="_blank">Full Text</a>]
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<a id="Yan2009" class="mim-anchor"></a>
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Yan, D., Ouyang, X., Patterson, D. M., Du, L. L., Jacobson, S. G., Liu, X.-Z.
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<strong>Mutation analysis in the long isoform of USH2A in American patients with Usher syndrome type II.</strong>
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J. Hum. Genet. 54: 732-738, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19881469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19881469</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19881469" 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/jhg.2009.107" target="_blank">Full Text</a>]
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<a id="Zlotogora2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zlotogora, J.
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<strong>Parents of children with autosomal recessive diseases are not always carriers of the respective mutant alleles.</strong>
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Hum. Genet. 114: 521-526, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15024643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15024643</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15024643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s00439-004-1105-y" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 02/02/2023
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Anne M. Lopez - updated : 10/11/2018<br>Nara Sobreira - updated : 11/10/2015<br>Marla J. F. O'Neill - updated : 6/11/2015<br>Cassandra L. Kniffin - updated : 1/9/2012<br>Marla J. F. O'Neill - updated : 5/3/2011<br>Cassandra L. Kniffin - updated : 6/14/2010<br>George E. Tiller - updated : 10/23/2009<br>George E. Tiller - updated : 7/20/2009<br>George E. Tiller - updated : 7/6/2009<br>Cassandra L. Kniffin - updated : 4/2/2009<br>Jane Kelly - updated : 11/30/2007<br>Cassandra L. Kniffin - updated : 10/10/2007<br>Patricia A. Hartz - updated : 4/30/2007<br>Cassandra L. Kniffin - updated : 12/28/2006<br>Marla J. F. O'Neill - updated : 3/13/2006<br>Marla J. F. O'Neill - updated : 6/2/2004<br>Victor A. McKusick - updated : 5/7/2004<br>Victor A. McKusick - updated : 4/22/2004<br>Victor A. McKusick - updated : 4/8/2004
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Creation Date:
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Cassandra L. Kniffin : 1/15/2004
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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carol : 04/18/2023
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<span class="mim-text-font">
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carol : 04/17/2023<br>alopez : 02/02/2023<br>carol : 03/15/2021<br>alopez : 10/11/2018<br>alopez : 02/19/2016<br>carol : 11/11/2015<br>carol : 11/10/2015<br>alopez : 6/11/2015<br>alopez : 4/23/2015<br>mcolton : 4/21/2015<br>alopez : 3/30/2015<br>carol : 6/18/2014<br>terry : 3/14/2013<br>terry : 8/31/2012<br>carol : 1/19/2012<br>carol : 1/19/2012<br>ckniffin : 1/9/2012<br>ckniffin : 1/9/2012<br>carol : 5/5/2011<br>terry : 5/5/2011<br>terry : 5/3/2011<br>terry : 5/3/2011<br>alopez : 3/15/2011<br>wwang : 6/21/2010<br>ckniffin : 6/14/2010<br>wwang : 11/4/2009<br>terry : 10/23/2009<br>alopez : 7/20/2009<br>alopez : 7/10/2009<br>terry : 7/6/2009<br>wwang : 6/23/2009<br>wwang : 4/17/2009<br>ckniffin : 4/2/2009<br>carol : 11/30/2007<br>carol : 11/29/2007<br>wwang : 10/17/2007<br>ckniffin : 10/10/2007<br>wwang : 4/30/2007<br>carol : 1/4/2007<br>ckniffin : 12/28/2006<br>ckniffin : 12/28/2006<br>wwang : 3/17/2006<br>terry : 3/13/2006<br>carol : 6/8/2004<br>terry : 6/2/2004<br>tkritzer : 5/24/2004<br>terry : 5/7/2004<br>tkritzer : 4/26/2004<br>terry : 4/22/2004<br>tkritzer : 4/16/2004<br>terry : 4/8/2004<br>carol : 4/8/2004<br>tkritzer : 2/20/2004<br>carol : 1/22/2004<br>ckniffin : 1/16/2004
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<span class="mim-font">
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<strong>*</strong> 608400
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USHERIN; USH2A
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<em>Alternative titles; symbols</em>
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USH2A GENE<br />
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USH2; US2
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: USH2A</em></strong>
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Cytogenetic location: 1q41
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Genomic coordinates <span class="small">(GRCh38)</span> : 1:215,622,891-216,423,448 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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<strong>Gene-Phenotype Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<span class="mim-font">
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1q41
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<span class="mim-font">
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Retinitis pigmentosa 39
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<span class="mim-font">
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613809
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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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Usher syndrome, type 2A
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<span class="mim-font">
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276901
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<span class="mim-font">
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Autosomal recessive
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<span class="mim-font">
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3
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<strong>TEXT</strong>
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<strong>Description</strong>
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<span class="mim-text-font">
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<p>Usherin is a transmembrane protein expressed in various tissues including retinal photoreceptors and cochlear hair cells, with a crucial role in photoreceptor survival and cochlear development (summary by Jung et al., 2023). </p>
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<div>
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<strong>Cloning and Expression</strong>
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<p>From the Usher syndrome type IIa (276901) critical region on chromosome 1 established by linkage studies, Eudy et al. (1998) identified the USH2A gene and isolated the corresponding cDNA from a human retina cDNA library. The USH2A gene encodes a 1,551-amino acid protein with a predicted molecular mass of 171.5 kD. Northern blot analysis identified 3 mRNA transcripts of 6.5, 5.0, and 1.9 kb in the retina. Reverse transcriptase PCR identified expression of USH2A in human fetal cochlea, eye, brain, and kidney. The USH2A protein sequence contains laminin epidermal growth factor and fibronectin type III motifs, which are most commonly observed in proteins comprising components of the basal lamina and extracellular matrices and in cell adhesion molecules. In the eye, both Bruch membrane (a specialized basement membrane underlying the retinal pigment epithelium) and the interphotoreceptor cell matrix are rich in extracellular matrix proteins. Extracellular matrix proteins also play a fundamental role in the cochlea: COL1A2 (120160), COL2A1 (120140), and COL3A1 (120180) are highly expressed in the membranous labyrinth of the cochlea. In addition, both X-linked and autosomal forms of Alport syndrome (see 104200) are caused by mutations in collagen type IV genes. </p><p>Weston et al. (2000) found a sequence difference in the USH2A gene, resulting in reduction of the total length of the encoded protein, which they designated usherin, from 1,551 to 1,546 amino acids. </p><p>Huang et al. (2002) isolated and characterized the mouse and rat orthologs of human USH2A. Like human USH2A, the mouse and rat genes are expressed primarily in retina and cochlea. Mouse Ush2a encodes a 161-kD protein that shows 68% identity and 9% similarity to the human USH2A protein. The predicted amino acid sequence of the mouse and rat proteins, like their human counterpart, contain a leader sequence, an amino-terminal globular domain, 10 laminin epidermal growth factor domains, and 4 carboxy-terminal fibronectin type III motifs. With in situ hybridization, the authors compared the cellular expression of the USH2A gene in rat, mouse, and human retinas. In all 3 species, Ush2a mRNA was expressed in cells of the outer nuclear layer of the retina, one of the target tissues of the disease. In the developing rat retina, Ush2a mRNA expression appeared in the neuroepithelium at embryonic day 17. </p><p>Van Wijk et al. (2004) identified novel exons in the USH2A gene and obtained evidence for alternative splicing. The putative 5,202-residue protein encoded by the longest open reading frame harbors, in addition to the known functional domains, 2 laminin G and 28 fibronectin type III repeats, as well as a transmembrane region followed by an intracellular domain with a PDZ-binding domain at its C-terminal end. Semiquantitative expression profile analysis suggested a low level of expression for both the long and the short isoform(s) and partial overlap in spatial and temporal expression patterns. </p><p>Using immunofluorescence microscopy in mouse retina, Liu et al. (2007) localized usherin to the apical inner segment recess that wraps around the connecting cilia, which links the inner and outer photoreceptor segments. Usherin also associated transiently with hair bundles in hair cells of the cochlea during early postnatal mouse development. </p>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Weston et al. (2000) determined that the usherin gene contains 21 exons. </p><p>Van Wijk et al. (2004) identified 51 additional exons at the 3-prime end of the USH2A gene, bringing the total number of exons to 72, and Adato et al. (2005) described a new alternatively spliced exon 71. </p>
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</span>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>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 fluorescence in situ hybridization, Huang et al. (2002) mapped the mouse Ush2a gene to chromosome 1 in a region syntenic to human chromosome 1q41. Rat Ush2a was localized by radiation hybrid analysis to rat chromosome 13. </p>
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</span>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Adato et al. (2005) described usherin alternative transcripts in the murine inner ear encoding several predicted transmembrane usherin isoforms with modular ectodomains of different lengths. They identified a 24-amino acid peptide, encoded by a novel exon, within the cytoplasmic region and found it to be predominantly expressed in the inner ear but not in the retina. In mouse and rat inner ears, a transmembrane usherin was present at the base of the differentiating stereocilia, which make up the mechanosensitive hair bundles receptive to sound. Usherin immunolabeling was transient in the hair bundles of cochlear hair cells (HCs), but persisted in mature hair bundles of vestibular HCs. Coimmunoprecipitation and in vitro binding assays demonstrated that the usherin cytodomain can bind to whirlin (WHRN; 607928) and harmonin (USH1C; 605242), 2 PDZ domain-containing proteins that are defective in genetic forms of isolated deafness (see 607084) and Usher type IC (276904), respectively. These PDZ proteins are suitable to provide the anchoring of interstereocilia lateral links to the F-actin core of stereocilia. The authors suggested that congenital deafness in Usher types I and II (see 276901) shares similar pathogenic mechanisms, i.e., the disruption of hair bundle links-mediated adhesion forces that are essential for the proper organization of growing hair bundles. </p><p>Reiners et al. (2005) demonstrated a molecular interaction between the scaffold protein harmonin, the USH2A protein usherin, 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>By yeast 2-hybrid analysis using deletion constructs of lebercilin (611408) and the intracellular region of USH2A isoform B, van Wijk et al. (2009) showed that the intermediate filament region of NLP(isoB) (NINL; 609580) interacts with lebercilin and USH2A(isoB), whereas no interaction was detected for NLP(isoA). Coimmunoprecipitation and GST pull-down assays confirmed interaction between NLP(isoB) and lebercilin and USH2A. Recombinant NLP(isoB), lebercilin, and USH2A(isoB) were all found to colocalize at the centrosomes in human retinal pigment epithelial (ARPE-19) cells. Staining of adult rat retinal sections with specific antibodies against all 3 proteins revealed their colocalization at the basal bodies of the photoreceptor-connecting cilia. A truncation mutation (611408.0003) in lebercilin reduced interaction and colocalization with NLP(isoB); however, RNAi knockdown of both endogenous NLP and lebercilin in ciliated ARPE-19 cells did not result in altered protein localization of NLP or lebercilin. </p><p>In coimmunoprecipitation studies, Ebermann et al. (2010) demonstrated interaction of USH2A with the first and second PDZ domains of PDZD7 (612971); a truncated version of USH2A without the C-terminal PDZ-binding motif showed reduced interaction. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Usher Syndrome Type IIA</em></strong></p><p>
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Among 96 patients with Usher syndrome type IIa (276901), Eudy et al. (1998) identified 3 mutations in the USH2A gene (608400.0001-608400.0003), all of which resulted in frameshifts and premature terminations. A 2299delG mutation (608400.0001), originally reported as 2314delG, was the most frequent mutant allele, occurring in 21 cases. </p><p>In a mutation search of 57 independent USH2A probands, Weston et al. (2000) identified 15 mutations in the USH2A gene. Of 114 independent USH2A alleles, 58 harbored probable pathologic mutations. Ten cases were true homozygotes and 10 were compound heterozygotes; 18 heterozygotes with only 1 identifiable mutation were observed. The 2299delG allele was the most frequent mutant allele, observed in 31 of 192 alleles (16%). </p><p>Dreyer et al. (2000) screened the USH2A gene for mutations in 31 unrelated patients from Denmark and Norway with Usher syndrome type II. The 2299delG mutation accounted for 44% of disease alleles. They found 16 novel putative disease-causing mutations, of which 12 were private and 4 were shared by unrelated patients. </p><p>In 12 unrelated patients with Usher syndrome, each with 1 mutation in exons 1 to 21 of the USH2A gene, van Wijk et al. (2004) identified a second pathogenic USH2A mutation in the 51 additional USH2A exons that they identified. The novel mutations included 3 different truncating mutations and 2 missense mutations (see, .e.g., 608400.0007-608400.0009). The presence of pathogenic mutations in the novel exons indicated that at least 1 of the putative long isoforms of the USH2A protein plays a role in both hearing and vision. </p><p>Aller et al. (2006) identified mutations in the USH2A gene in 14 of 32 unrelated Spanish patients with Usher syndrome, nonsyndromic retinal degeneration, or nonsyndromic deafness in whom 2 disease-causing mutations could not be found after screening the first 21 exons of the USH2A gene. Analysis of the 51 new exons identified by van Wijk et al. (2004) and the 1 new exon identified by Adato et al. (2005) yielded 14 novel mutations, including 7 missense, 5 frameshift, 1 duplication, and 1 putative splice site mutation. Most of the patients had previously been reported by Aller et al. (2004). All of the individuals with 2 mutations were clinically diagnosed with Usher syndrome type IIa. </p><p>Baux et al. (2007) identified 34 distinct mutations in the USH2A gene in affected individuals from 25 families with Usher syndrome. Two of the alleles were complex with 3 and 2 mutations in cis, respectively. Only 5 families carried both mutations in the first 21 exons, indicating that screening of the entire gene is necessary for accurate and complete mutational analysis. </p><p>To explore the spectrum of USH2A disease-causing mutations among Scandinavian USH2 cases, Dreyer et al. (2008) performed extensive DNA sequence analysis of the full-size USH2A gene in patients from 118 unrelated families, of which 27 had previously been found to carry mutations in exons 1 to 21. In all, 122 USH2A DNA sequence alterations were identified, of which 57 were predicted to be pathogenic, 7 were considered to be of uncertain pathogenicity, and 58 were predicted to be benign variants. Of 36 novel pathogenic USH2A mutations, 31 were located in exons 22 to 73, specific to the long isoform (see, e.g., 608400.0013). USH2A mutations were identified in 89 (75.4%) of 118 families. In 79 (88.8%) of these 89 families, 2 pathogenic mutations were identified, whereas in 10 families (11.2%) the second mutation remained unidentified. In 5 (4.2%) of the 118 families the USH phenotype could be explained by mutations in the CLRN1 gene (606397). </p><p>Yan et al. (2009) identified mutant USH2A alleles in 12 (60%) of 20 American patients of European ancestry with Usher syndrome type IIa. Seven (35%) patients had only 1 pathogenic mutation, and 8 patients did not have USH2A mutations. There were 5 novel mutations and 5 previously reported mutations, consisting of 3 missense, 3 frameshift, and 4 nonsense. The 2299delG mutation was the most common, accounting for 38.9% of mutant alleles. </p><p>McGee et al. (2010) screened the long isoform of USH2A in 108 patients diagnosed with Usher syndrome type IIa and identified at least 1 deleterious mutation in at least 57% of cases. </p><p><strong><em>Retinitis Pigmentosa 39</em></strong></p><p>
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Rivolta et al. (2002) identified autosomal recessive retinitis pigmentosa (RP39; 613809) without hearing loss due to mutation in the USH2A gene inherited by uniparental paternal disomy (C759F; 608400.0006). Zlotogora (2004) reviewed examples in which uniparental disomy had been established as the cause of an autosomal recessive disorder. One of 6 such disorders listed for chromosome 1, the most for any single chromosome, was autosomal recessive retinitis pigmentosa without hearing loss due to mutation in the USH2A gene. </p><p>McGee et al. (2010) screened the long isoform of USH2A in 80 patients with nonsyndromic autosomal recessive RP and identified at least 1 deleterious mutation in 19% of cases. The authors stated that their findings supported USH2A as the most common known cause of RP in the United States. </p><p>In a cohort of 94 Korean probands with RP, Jung et al. (2023) analyzed the USH2A gene and identified 10 probands who were compound heterozygous for mutations in the USH2A gene (e.g., 608400.0016-608400.0018). Hearing tests were not performed because no hearing problems were reported by any of the probands. </p><p><strong><em>Cosegregation of Usher Syndrome and Retinitis Pigmentosa</em></strong></p><p>
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In a consanguineous family of Iraqi Jewish origin in which some members had USH2 and others had nonsyndromic retinitis pigmentosa, Kaiserman et al. (2007) identified 3 pathogenic mutations in the USH2A gene. Patients with USH2A were compound heterozygous for 2 null mutations (608400.0010-608400.0011), whereas patients with nonsyndromic RP were compound heterozygous for 1 of the null mutations and a novel missense mutation (608400.0012). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Genotype/Phenotype Correlations</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>To investigate genotype/phenotype correlations, Aller et al. (2004) screened 191 unrelated Spanish patients with syndromic or nonsyndromic retinal diseases, or with nonsyndromic hearing impairment, for the 2299delG (608400.0001) and C759F (608400.0006) mutations in the USH2A gene. They found that the 2299delG mutation was present in patients with clinical signs of Usher syndrome type II or of atypical Usher syndrome, whereas the C759F mutation, whether or not it was associated with the 2299delG mutation, was identified in cases with nonsyndromic retinitis pigmentosa (RP). Aller et al. (2004) concluded that sensorineural hearing loss in patients with RP may depend on the nature and association of the USH2A allelic variants present. </p><p>Bernal et al. (2005) studied 28 Spanish patients with Usher syndrome type II, identifying 10 different pathogenic mutations and 17 polymorphisms in the USH2A gene. They observed discordant phenotypes in sib pairs from 2 unrelated families and noted that Liu et al. (1999) had reported clinical differences in monozygotic twins with Usher syndrome type II and had suggested that variation in the expression of the USH2A gene is not determined simply by genetic factors. </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>Liu et al. (2007) found that Ush2a knockout in mice led to progressive photoreceptor degeneration and a moderate but nonprogressive hearing impairment, mimicking the visual and hearing defects in USH2A patients. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<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>18 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 IIA</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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USH2A, 1-BP DEL, 2299G
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<br />
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SNP: rs80338903,
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gnomAD: rs80338903,
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ClinVar: RCV000002445, RCV000032524, RCV000191141, RCV000210326, RCV000254870, RCV000504641, RCV000623326, RCV000678639, RCV000735362, RCV000787895, RCV000787897, RCV000787899, RCV000824793, RCV001000453, RCV001095692, RCV002504737
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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>By heteroduplex analysis, Eudy et al. (1998) identified a 2299delG mutation (originally reported by them as 2314delG) in the USH2A gene in 21 of 96 probands with Usher syndrome type IIa (USH2A; 276901); 8 of them were homozygous and 13 heterozygous. All but 2 were of northern European ancestry (Swedish, Dutch, German, or English). The 2 non-northern European patients were both homozygous for the 2299G deletion; one was from Spain and the other was an African American from Nebraska, U.S. Examination of various haplotypes failed to reveal any substantial disequilibrium with the 2299delG mutation, suggesting that the mutation did not arise in a common ancestor. The 2299delG mutation caused a frameshift at codon 772, after which the open reading frame continued for 20 codons and ended as TAG. </p><p>Liu et al. (1999) performed a mutation analysis of the USH2A gene in 23 families with Usher syndrome, 10 of which had a diagnosis of atypical Usher syndrome, from the United Kingdom and China. They found that most of the families with USH2 carried the 2299delG mutation. Of 12 families with the 2299delG mutation, 8 families had the typical USH2 phenotype (congenital moderate to severe hearing impairment, normal vestibular function, and postpubertal onset of retinitis pigmentosa). However, 5 affected individuals from the remaining 4 families carrying the 2299delG mutation showed atypical Usher syndrome features, with progressive hearing impairment, variable vestibular function, and RP. An isolated patient with the mutation was typical of USH2 in all aspects, including nonprogressive hearing loss, but had absent vestibular function, which is a critical discriminator in clinical classification. </p><p>Weston et al. (2000) revised numbering for the sequence of the USH2A gene, taking into account a significant sequence difference. The 2299delG mutation reported by Eudy et al. (1998) is correctly referred to as 2299delG. The sequence difference reduces the length of the usherin protein from 1551 to 1546 amino acids. </p><p>Weston et al. (2000) found the 2299delG mutation to be the most frequent, having a frequency of 31 in 192 alleles (16%) in their series. </p><p>Dreyer et al. (2001) presented data indicating that the widespread geographic distribution of the 2299delG mutation is the result of an ancestral mutation that spread throughout Europe and into the New World as a result of migration. Various studies had reported a range of frequencies (from 0.16 to 0.44) among patients with Usher syndrome, depending on the geographic origin of the patients. Dreyer et al. (2001) performed haplotype analysis on DNA samples from 116 unrelated patients with Usher syndrome type IIa; the patients were from 14 countries and represented 148 2299delG alleles. On the basis of 6 single-nucleotide polymorphisms (SNPs) within the USH2A gene, 12 core haplotypes were observed in a panel of normal chromosomes. However, in their patient analysis, only 1 core haplotype was associated with the 2299delG mutation. </p><p>Ouyang et al. (2004) confirmed that 2299delG is the most common mutation in USH2A, accounting for 77.5% of the pathologic alleles. In 5 of the 24 patients, the 2299delG mutation was present in homozygous state; in 3 it was present in compound heterozygous state with other mutations; and in 16 it was present in heterozygous state. </p><p>Baux et al. (2007) identified the 2299delG mutation, which results in a frameshift at codon 767, in 22% of mutated alleles in their study of 25 affected families. </p><p>Yan et al. (2009) identified the 2299delG mutation in 38.9% of mutant alleles among 12 American probands of European descent with Usher syndrome type IIa. </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 IIA</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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USH2A, 1-BP DEL, 2898G
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<br />
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SNP: rs397518008,
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ClinVar: RCV000002446, RCV000671576, RCV000824792, RCV001851582, RCV003450613
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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 IIa (USH2A; 276901), Eudy et al. (1998) found a 1-bp deletion, reported by them as 2913delG, in the USH2A gene. This mutation is correctly referred to as 2898delG (T967FS) (Weston et al., 2000). </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 IIA</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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USH2A, 2-BP DEL, 4338CT
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<br />
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SNP: rs111033367,
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gnomAD: rs111033367,
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ClinVar: RCV000002447, RCV000310917, RCV000710335, RCV000793722, RCV000984013, RCV001073308, RCV002482816
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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 the Louisiana Acadian population with Usher syndrome type IIa (USH2A; 276901), Eudy et al. (1998) found heterozygosity for a dinucleotide deletion that they reported as 4353-4delCT. This mutation is correctly referred to as 4338-9delCT (C1447FS) (Weston et al., 2000). </p><p>Ebermann et al. (2009) identified the homozygous 4338delCT mutation in 4 of 9 French Canadian families with Usher syndrome type IIa from Quebec and New Brunswick, the former Acadia. Affected individuals from 2 additional families carried the mutation in heterozygosity. Altogether, the 4338delCT mutation accounted for 10 (55.6%) of 18 disease alleles. Haplotype analysis indicated a founder effect. The findings indicated that the Acadian and Quebec populations share common ancestors. </p><p>Ebermann et al. (2010) studied 2 French Canadian sisters with USH2A who were homozygous for the 4338delCT mutation in the USH2A gene, and identified an additional de novo heterozygous frameshift mutation in the PDZD7 gene (612971.0001) in 1 of the sisters, who had earlier-onset and more severe retinal disease. The PDZD7 mutation was not present in the other sister, who had a much milder retinal phenotype. Ebermann et al. (2010) concluded that PDZD7 is a retinal disease modifier in patients with USH2A. </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 IIA</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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USH2A, LEU260TER
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<br />
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SNP: rs121912598,
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gnomAD: rs121912598,
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ClinVar: RCV000002448
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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 members of a Swedish family with type IIa Usher syndrome (USH2A; 276901), Weston et al. (2000) identified a 779T-G transversion in the USH2A gene, resulting in a leu260-to-ter (L260X) change. The mutation was present in compound heterozygous state with the 2299delG mutation (608400.0001). </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 IIA</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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USH2A, CYS319TYR
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<br />
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SNP: rs121912599,
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gnomAD: rs121912599,
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ClinVar: RCV000002449, RCV000303941, RCV000824798, RCV001004780, RCV001074393, RCV003460406, RCV005007808
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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>Weston et al. (2000) found homozygosity for a cys319-to-tyr (C319Y) mutation in the USH2A gene in a proband with Usher syndrome type IIa (USH2A; 276901) from a Hispanic American 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>.0006 RETINITIS PIGMENTOSA 39</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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USH2A, CYS759PHE ({dbSNP rs80338902})
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<br />
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SNP: rs80338902,
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gnomAD: rs80338902,
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ClinVar: RCV000002450, RCV000032523, RCV000174625, RCV000239000, RCV000404009, RCV000504814, RCV000505146, RCV000623925, RCV001257905, RCV001535506, RCV001813938, RCV002251859
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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>Rivolta et al. (2000) described a cys759-to-phe (C759F) missense mutation caused by a G-T change in the USH2A gene that was associated with autosomal recessive retinitis pigmentosa without hearing loss (RP39; 613809). The amino acid at this position is within the fifth laminin-epidermal growth factor-like domain and participates in a presumed disulfide bridge. The mutation was found in 4.5% of 224 patients with recessive RP. </p><p>Rivolta et al. (2002) reported a patient with RP without hearing loss caused by a homozygous C759F mutation in the USH2A gene. Her father was heterozygous for this change, and her mother was a noncarrier. Further evaluation with microsatellite markers revealed that the patient had inherited 2 copies of chromosome 1 from her father and none from her mother. The 2 paternally derived copies of chromosome 1 were heteroallelic from the centromere to the proximal short and long arms. The distal regions of the short and long arms of chromosome 1 were homoallelic, including the region of 1q with the mutant USH2A allele. This genetic pattern is compatible with uniparental primary heterodisomy with regions of homozygosity arising through a nondisjunction event during paternal meiosis I and subsequent trisomy rescue or gamete complementation. A paternal second cousin of the patient also had RP and had an identical heterozygous mutation in the USH2A gene in the same codon. However, the analysis of an isocoding polymorphism 20 bp away and closely linked microsatellite markers in the patient and family members indicated that the 2 mutant alleles were unlikely to be identical by descent and that the 2 relatives fortuitously had RP and a mutation in the same codon of the USH2A gene. </p><p>Pozo et al. (2015) noted that 15 families with RP had been reported to have a homozygous C759F variant (rs80338902) in the USH2A gene. In all reviewed cases, the segregation data either were not shown or were inconclusive. Pozo et al. (2015) restudied a Spanish family (S23) in which Bernal et al. (2003) had identified homozygosity for C759F in 2 affected and 2 unaffected sibs. By next-generation sequencing, they identified homozygosity for an R560C mutation in the PDE6B gene (180072.0008) that segregated with the disorder in the family and was absent in 200 control individuals. Pozo et al. (2015) suggested that the C759F variant might not be pathogenic and proposed genetic reevaluation of other reported families with the C759F variant. </p><p>In a discovery cohort of 186 unrelated probands with autosomal recessive retinal degeneration without childhood hearing loss, Lenassi et al. (2015) found the c.2276G-T transversion in USH2A gene, resulting in a C759F substitution, in 11 alleles (once in homozygosity). In the replication cohort of 84 unrelated probands with autosomal recessive retinal degeneration, the allele was found 5 times, once in homozygosity; and in a third panel of 187 patients with nonsyndromic adult-onset autosomal recessive retinitis pigmentosa, it was found 5 times, once in homozygosity. Lenassi et al. (2015) noted that the C759F mutation is often considered to be the most common disease-causing variant in patients with nonsyndromic retinitis pigmentosa. </p><p>To assess the role of the C759F mutation in autosomal recessive retinitis pigmentosa and Usher syndrome type 2, Perez-Carro et al. (2018) performed a comprehensive genetic and clinical study of 57 families with affected members who carried the C759F mutation on at least 1 allele. Of the 57 probands, 11 were homozygous for the mutation, 42 were compound heterozygous with another mutation in the USH2A gene, and the remaining 4 also carried mutations in RP1 (603937), PROM1 (604365), or CNGB1 (600724). The 2 patients with PROM1 and CNGB1 mutations, and 1 patient with mutated RP1, were homozygous for those mutations in addition to the C759F mutation in USH2A; the second patient with mutation in RP1 was heterozygous for that mutation. The authors noted that although the C759F variant is enriched in the Spanish population, no homozygous individuals had been identified in control populations, even in Spanish population databases. Perez-Carro et al. (2018) stated that the C759F mutation alters a highly conserved residue in a domain that enhances USH2A stability in the basement membrane by prompting its interaction with collagen IV (see 120070). The mutation was also predicted to disrupt a disulfide bridge, leading to erroneous protein folding and instability. While Pozo et al. (2015) had questioned the pathogenicity of the C759F variant, at least in homozygosity, Perez-Carro et al. (2018) pointed out that no other candidate variants in the USH2A or any other RP genes that could explain the phenotypes were found in their patients by next-generation sequencing. They concluded that C759F homozygosity is associated with a later diagnosis of RP and slower progression of visual field loss, with a very late hypoacusis diagnosis (around the seventh decade). </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 IIA</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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USH2A, TRP3955TER
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<br />
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SNP: rs111033364,
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gnomAD: rs111033364,
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ClinVar: RCV000002451, RCV000412373, RCV000414231, RCV000414867, RCV000415089, RCV000504922, RCV000824781, RCV001003260, RCV001074873, RCV001813732, RCV002476913, RCV003114173, RCV003314546, RCV004584307
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 patients with Usher syndrome type IIa (USH2A; 276901), van Wijk et al. (2004) found compound heterozygosity for a trp3955-to-ter (W3955X) mutation in the USH2A gene and 2 different mutations: a 949C-A transversion in one patient, resulting in an arg317-to-arg mutation (R317R; 608400.0008), which was predicted to create an additional 5-prime splice site in exon 5; and a 1256G-T transversion, resulting in a cys419-to-phe substitution (C419F; 608400.0009) in the second patient. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0008 USHER SYNDROME, TYPE IIA</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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USH2A, 949C-A, ARG317ARG
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<br />
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SNP: rs111033272,
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gnomAD: rs111033272,
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ClinVar: RCV000002452, RCV000412796, RCV000627017, RCV000763297, RCV000824799, RCV000984234, RCV001075725, RCV001199595
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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>For discussion of the arg317-to-arg (R317R) mutation in the USH2A gene that was found in compound heterozygous state in patients with Usher syndrome type IIa (USH2A; 276901) by van Wijk et al. (2004), see 608400.0007. </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>.0009 USHER SYNDROME, TYPE IIA</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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USH2A, CYS419PHE
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<br />
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SNP: rs121912600,
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gnomAD: rs121912600,
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ClinVar: RCV000002453, RCV000224697, RCV000504809, RCV000778222, RCV000824795, RCV000984315, RCV001074823, RCV002482817
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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>For discussion of the cys419-to-phe (C419F) mutation in the USH2A gene that was found in compound heterozygous state in patients with Usher syndrome type IIa (USH2A; 276901) by van Wijk et al. (2004), see 608400.0007. </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>.0010 USHER SYNDROME, TYPE IIA</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">
|
|
RETINITIS PIGMENTOSA 39, INCLUDED
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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USH2A, 4-BP INS, NT239
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<br />
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SNP: rs587776538,
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ClinVar: RCV000002454, RCV000002455
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a consanguineous family of Iraqi Jewish origin in which some members had Usher syndrome type IIa (USH2A; 276901) and others had nonsyndromic retinitis pigmentosa (RP39; 613809), Kaiserman et al. (2007) identified compound heterozygosity for 2 null mutations in the USH2A gene in those affected with USH2A: a 4-bp insertion (239_242insCGAT) resulting in a frameshift at position 80 (Thr80fs), and a 2209C-T transition resulting in an arg737-to-ter (R737X; 608400.0011) substitution. In those affected with nonsyndromic RP, they identified compound heterozygosity for one of the null mutations and a 14021A-G transition resulting in an arg4674-to-gly substitution (R4674G; 608400.0012). </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>.0011 USHER SYNDROME, TYPE IIA</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">
|
|
RETINITIS PIGMENTOSA 39, INCLUDED
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
|
USH2A, ARG737TER
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<br />
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SNP: rs111033334,
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gnomAD: rs111033334,
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ClinVar: RCV000002456, RCV000002457, RCV000725261, RCV000824794, RCV001003279
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|
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|
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</span>
|
|
</div>
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|
|
<div>
|
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<span class="mim-text-font">
|
|
<p>For discussion of the arg737-to-ter (R737X) mutation in the USH2A gene that was found in compound heterozygous state in a family in which some members had Usher syndrome type IIa (USH2A; 276901) and others had nonsyndromic retinitis pigmentosa (RP39; 613809) by Kaiserman et al. (2007), see 608400.0010. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
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<br />
|
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 RETINITIS PIGMENTOSA 39</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
USH2A, ARG4674GLY
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<br />
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SNP: rs80338904,
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|
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gnomAD: rs80338904,
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|
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|
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ClinVar: RCV000002458, RCV000032522, RCV001379272
|
|
|
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|
|
</span>
|
|
</div>
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|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg4674-to-gly (R4674G) mutation in the USH2A gene that was found in compound heterozygous state in a family in which some members had Usher syndrome type IIa (USH2A; 276901) and others had nonsyndromic retinitis pigmentosa (RP39; 613809) by Kaiserman et al. (2007), see 608400.0010. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
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<div>
|
|
<br />
|
|
</div>
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|
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</div>
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<div>
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 USHER SYNDROME, TYPE IIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
USH2A, IVS40AS, A-G, -2144
|
|
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|
<br />
|
|
|
|
SNP: rs786200928,
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|
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|
|
|
gnomAD: rs786200928,
|
|
|
|
|
|
ClinVar: RCV000023700, RCV000505092, RCV000664608, RCV000787740, RCV000814767, RCV001003267, RCV001074209, RCV001376510, RCV001824575, RCV004017262
|
|
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|
|
</span>
|
|
</div>
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|
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a French patient with Usher syndrome type IIa (USH2A; 276901), Vache et al. (2012) identified compound heterozygosity for 2 mutations in the USH2A gene: a heterozygous A-to-G transition deep within intron 40 (c.7595-2144) and a 1-bp duplication (3129dupT; 608400.0014), resulting in a frameshift. Two other individuals in a different branch of the family had the intron 41 mutation and a different heterozygous frameshift mutation, 8890dupT (608400.0015). The intron 41 mutation was found only after RT-PCR amplification of RNA from nasal cells in 1 patient showed an aberrant USH2A out-of-frame transcript predicted to result in a truncated protein that would not be anchored to the cell membrane. DNA studies showed that the A-to-G transition resulted in activation of a pseudoexon between exons 40 and 41, causing a 153-bp insertion and a frameshift. The nomenclature used for this insertion was r.7594_7595ins7595-2296_7595-2143. This mutation was not found in 338 alleles. However, this mutation was found in 4 of 20 USH2A patients with no identified mutation or only a single pathogenic mutation, as well as in 4 of 18 Spanish patients with incomplete USH2A genotypes. Vache et al. (2012) noted that the identification of a deep intronic mutation in a pseudoexon raised the possibility of a new therapeutic strategy using antisense oligonucleotide chemistry to restore normal splicing via exon skipping. </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>.0014 USHER SYNDROME, TYPE IIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
USH2A, 1-BP DUP, 3129T
|
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|
|
|
<br />
|
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|
|
SNP: rs786205115,
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|
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gnomAD: rs786205115,
|
|
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|
|
|
ClinVar: RCV000023701
|
|
|
|
|
|
</span>
|
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</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 1-bp duplication in the USH2A gene (3129dupT) that was found in compound heterozygous state in a patient with Usher syndrome type IIa (USH2A; 276901) by Vache et al. (2012), see 608400.0013. </p>
|
|
</span>
|
|
</div>
|
|
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|
<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 USHER SYNDROME, TYPE IIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
USH2A, 1-BP DUP, 8890T
|
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<br />
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|
|
SNP: rs786205116,
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|
|
gnomAD: rs786205116,
|
|
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|
|
ClinVar: RCV000023702, RCV002513202
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 1-bp duplication in the USH2A gene (8890dupT) that was found in compound heterozygous state in patients with Usher syndrome type IIa (USH2A; 276901) by Vache et al. (2012), see 608400.0013. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
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</div>
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|
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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>.0016 RETINITIS PIGMENTOSA 39</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
USH2A, CYS934TRP
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<br />
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SNP: rs201527662,
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gnomAD: rs201527662,
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ClinVar: RCV000132710, RCV000576637, RCV000595137, RCV000986542, RCV001003277, RCV001074347, RCV002469023, RCV004796037
|
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|
|
|
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</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 Korean probands with retinitis pigmentosa (RP39; 613809), Jung et al. (2023) identified compound heterozygosity for a c.2802T-G transversion in exon 13 of the USH2A gene, resulting in a cys934-to-trp (C934W) substitution within the LamE 8 domain, and another missense or truncating mutation in the USH2A gene (e.g., 608400.0017 and 608400.0018). Hearing tests were not performed, but no hearing problems were reported by any of the probands. </p>
|
|
</span>
|
|
</div>
|
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|
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<div>
|
|
<br />
|
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</div>
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|
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</div>
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<div>
|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 RETINITIS PIGMENTOSA 39</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
|
|
|
|
USH2A, 4-BP DEL, 13112AAAT
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<br />
|
|
|
|
SNP: rs768161313,
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gnomAD: rs768161313,
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ClinVar: RCV000674880, RCV000734827, RCV000985058, RCV003223665, RCV003889966, RCV004535690
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 Korean probands with retinitis pigmentosa (RP39; 613809), Jung et al. (2023) identified compound heterozygosity for a 4-bp deletion (c.13112_13115delAAAT) in exon 63 of the USH2A gene, causing a frameshift predicted to result in a premature termination codon (Gln4371fs), and another missense or truncating mutation in the USH2A gene (e.g., 608400.0016). Hearing tests were not performed, but no hearing problems were reported by the probands. </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>.0018 RETINITIS PIGMENTOSA 39</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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USH2A, ARG1578CYS
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<br />
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SNP: rs201529124,
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gnomAD: rs201529124,
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ClinVar: RCV001067861, RCV001376322, RCV002282450, RCV003455294, RCV004813699, RCV005021413
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 Korean probands with retinitis pigmentosa (RP39; 613809), Jung et al. (2023) identified compound heterozygosity for a c.4732C-T transition in exon 22 of the USH2A gene, resulting in an arg1578-to-cys (R1578C) substitution within the LamG 1 domain, and another missense or truncating mutation in the USH2A gene (e.g., 608400.0016). Hearing tests were not performed, but no hearing problems were reported by the probands. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Adato, A., Lefevre, G., Delprat, B., Michel, V., Michalski, N., Chardenoux, S., Weil, D., El-Amraoui, A., Petit, C.
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<strong>Usherin, the defective protein in Usher syndrome type IIA, is likely to be a component of interstereocilia ankle links in the inner ear sensory cells.</strong>
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Hum. Molec. Genet. 14: 3921-3932, 2005.
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[PubMed: 16301217]
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[Full Text: https://doi.org/10.1093/hmg/ddi416]
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<p class="mim-text-font">
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Aller, E., Jaijo, T., Beneyto, M., Najera, C., Oltra, S., Ayuso, C., Baiget, M., Carballo, M., Antinolo, G., Valverde, D., Moreno, F., Vilela, C., Collado, D., Perez-Garrigues, H., Navea, A., Millan, J. M.
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<strong>Identification of 14 novel mutations in the long isoform of USH2A in Spanish patients with Usher syndrome type II.</strong>
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J. Med. Genet. 43: e55, 2006. Note: Electronic Article.
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[Full Text: https://doi.org/10.1136/jmg.2006.041764]
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Aller, E., Najera, C., Millan, J. M., Oltra, J. S., Perez-Garrigues, H., Vilela, C., Navea, A., Beneyto, M.
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<strong>Genetic analysis of 2299delG and C759F mutations (USH2A) in patients with visual and/or auditory impairments.</strong>
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Europ. J. Hum. Genet. 12: 407-410, 2004.
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[PubMed: 14970843]
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Baux, D., Larrieu, L., Blanchet, C., Hamel. C., Ben Salah, S., Vielle, A., Gilbert-Dussardier, B., Holder, M., Calvas, P., Philip, N., Edery, P., Bonneau, D., Claustres, M., Malcolm, S., Roux, A.-F.
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<strong>Molecular and in silico analyses of the full-length isoform of usherin identify new pathogenic alleles in Usher type II patients.</strong>
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Hum. Mutat. 28: 781-789, 2007.
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[PubMed: 17405132]
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[Full Text: https://doi.org/10.1002/humu.20513]
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Bernal, S., Ayuso, C., Antinolo, G., Gimenez, A., Borrego, S., Trujillo, M. J., Marcos, I., Calaf, M., Del Rio, E., Baiget, M.
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<strong>Mutations in USH2A in Spanish patients with autosomal recessive retinitis pigmentosa: high prevalence and phenotypic variation.</strong>
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[PubMed: 12525556]
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[Full Text: https://doi.org/10.1136/jmg.40.1.e8]
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Bernal, S., Meda, C., Solans, T., Ayuso, C., Garcia-Sandoval, B., Valverde, D., Del Rio, E., Baiget, M.
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<strong>Clinical and genetic studies in Spanish patients with Usher syndrome type II: description of new mutations and evidence for a lack of genotype-phenotype correlation.</strong>
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Clin. Genet. 68: 204-214, 2005.
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[PubMed: 16098008]
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[Full Text: https://doi.org/10.1111/j.1399-0004.2005.00481.x]
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Dreyer, B., Brox, V., Tranebjaerg, L., Rosenberg, T., Sadeghi, A. M., Moller, C., Nilssen, O.
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<strong>Spectrum of USH2A mutations in Scandinavian patients with Usher syndrome type II.</strong>
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Hum. Mutat. 29: 451 only, 2008. Note: Full article online.
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[PubMed: 18273898]
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[Full Text: https://doi.org/10.1002/humu.9524]
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Dreyer, B., Tranebjaerg, L., Brox, V., Rosenberg, T., Moller, C., Beneyto, M., Weston, M. D., Kimberling, W. J., Nilssen, O.
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<strong>A common ancestral origin of the frequent and widespread 2299delG USH2A mutation.</strong>
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Am. J. Hum. Genet. 69: 228-234, 2001. Note: Erratum: Am. J. Hum. Genet. 69: 922 only, 2001.
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[PubMed: 11402400]
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[Full Text: https://doi.org/10.1086/321269]
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Dreyer, B., Tranebjaerg, L., Rosenberg, T., Weston, M. D., Kimberling, W. J., Nilssen, O.
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[PubMed: 10909849]
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Ebermann, I., Koenekoop, R. K., Lopez, I., Bou-Khzam, L., Pigeon, R., Bolz, H. J.
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<strong>An USH2A founder mutation is the major cause of Usher syndrome type 2 in Canadians of French origin and confirms common roots of Quebecois and Acadians.</strong>
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Europ. J. Hum. Genet. 17: 80-84, 2009.
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[Full Text: https://doi.org/10.1038/ejhg.2008.143]
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Ebermann, I., Phillips, J. B., Liebau, M. C., Koenekoop, R. K., Schermer, B., Lopez, I., Schafer, E., Roux, A.-F., Dafinger, C., Bernd, A., Zrenner, E., Claustres, M., Blanco, B., Nurnberg, G., Nurnberg, P., Ruland, R., Westerfield, M., Benzing, T., Bolz, H. J.
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<strong>PDZD7 is a modifier of retinal disease and a contributor to digenic Usher syndrome.</strong>
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Eudy, J. D., Weston, M. D., Yao, S., Hoover, D. M., Rehm, H. L., Ma-Edmonds, M., Yan, D., Ahmad, I., Cheng, J. J., Ayuso, C., Cremers, C., Davenport, S., Moller, C., Talmadge, C. B., Beisel, K. W., Tamayo, M., Morton, C. C., Swaroop, A., Kimberling, W. J., Sumegi, J.
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<strong>Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa.</strong>
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Science 280: 1753-1757, 1998.
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Huang, D., Eudy, J. D., Uzvolgyi, E., Davis, J. R., Talmadge, C. B., Pretto, D., Weston, M. D., Lehman, J. E., Zhou, M., Seemayer, T. A., Ahmad, I., Kimberling, W. J., Sumegi, J.
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<strong>Identification of the mouse and rat orthologs of the gene mutated in Usher syndrome type IIA and the cellular source of USH2A mRNA in retina, a target tissue of the disease.</strong>
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Genomics 80: 195-203, 2002.
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Jung, S., Park, Y. C., Lee, D., Kim, S., Kim, S.-M., Kim, Y., Lee, D., Hyun, J., Koh, I., Lee, J.-Y.
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<strong>Exome sequencing identified five novel USH2A variants in Korean patients with retinitis pigmentosa.</strong>
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Kaiserman, N., Obolensky, A., Banin, E., Sharon, D.
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<strong>Novel USH2A mutations in Israeli patients with retinitis pigmentosa and Usher syndrome type 2.</strong>
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Lenassi, E., Vincent, A., Li, Z., Saihan, Z., Coffey, A. J., Steele-Stallard, H. B., Moore, A. T., Steel, K. P., Luxon, L. M., Heon, E., Bitner-Glindzicz, M., Webster, A. R.
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<strong>A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants.</strong>
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<p class="mim-text-font">
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Liu, X., Bulgakov, O. V., Darrow, K. N., Pawlyk, B., Adamian, M., Liberman, M. C., Li, T.
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<p class="mim-text-font">
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Liu, X.-Z., Hope, C., Liang, C. Y., Zou, J. M., Xu, L. R., Cole, T., Mueller, R. F., Bundey, S., Nance, W., Steel, K. P., Brown, S. D. M.
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<strong>A mutation (2314delG) in the Usher syndrome type IIA gene: high prevalence and phenotypic variation. (Letter)</strong>
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Am. J. Hum. Genet. 64: 1221-1225, 1999.
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[PubMed: 10090909]
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<p class="mim-text-font">
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McGee, T. L., Seyedahmadi, B. J., Sweeney, M. O., Dryja, T. P., Berson, E. L.
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<strong>Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome type II or non-syndromic retinitis pigmentosa.</strong>
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J. Med. Genet. 47: 499-506, 2010.
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[PubMed: 20507924]
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[Full Text: https://doi.org/10.1136/jmg.2009.075143]
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<p class="mim-text-font">
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Ouyang, X. M., Yan, D., Hejtmancik, J. F., Jacobson, S. G., Li, A. R., Du, L. L., Angeli, S., Kaiser, M., Balkany, T., Liu, X. Z.
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<strong>Mutational spectrum in Usher syndrome type II.</strong>
|
|
Clin. Genet. 65: 288-293, 2004. Note: Erratum: Clin. Genet. 65: 433 only, 2004.
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[PubMed: 15025721]
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[Full Text: https://doi.org/10.1046/j.1399-0004.2004.00216.x]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Perez-Carro, R., Blanco-Kelly, F., Galbis-Martinez, L., Garcia-Garcia, G., Aller, E., Garcia-Sandoval, B., Minguez, P., Corton, M., Mahillo-Fernandez, I., Martin-Merida, I., Avila-Fernandez, A., Millan, J. M., Ayuso, C.
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|
<strong>Unravelling the pathogenic role and genotype-phenotype correlation of the USH2A p.(cys759phe) variant among Spanish families.</strong>
|
|
PLoS One 13: e0199048, 2018. Note: Electronic Article.
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|
|
[PubMed: 29912909]
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[Full Text: https://doi.org/10.1371/journal.pone.0199048]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
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Pozo, M. G., Bravo-Gil, N., Mendez-Vidal, C., Montero-de-Espinosa, I., Millan, J. M., Dopazo, J., Borrego, S., Antinolo, G.
|
|
<strong>Re-evaluation casts doubt on the pathogenicity of homozygous USH2A p.C759F.</strong>
|
|
Am. J. Med. Genet. 167A: 1597-1600, 2015.
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|
|
[PubMed: 25823529]
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[Full Text: https://doi.org/10.1002/ajmg.a.37003]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
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: 16301216]
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|
|
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|
|
[Full Text: https://doi.org/10.1093/hmg/ddi417]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Rivolta, C., Berson, E. L., Dryja, T. P.
|
|
<strong>Paternal uniparental heterodisomy with partial isodisomy of chromosome 1 in a patient with retinitis pigmentosa without hearing loss and a missense mutation in the Usher syndrome type II gene USH2A.</strong>
|
|
Arch. Ophthal. 120: 1566-1571, 2002.
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|
|
[PubMed: 12427073]
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|
[Full Text: https://doi.org/10.1001/archopht.120.11.1566]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Rivolta, C., Sweklo, E. A., Berson, E. L., Dryja, T. P.
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|
<strong>Missense mutation in the USH2A gene: association with recessive retinitis pigmentosa without hearing loss.</strong>
|
|
Am. J. Hum. Genet. 66: 1975-1978, 2000.
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[PubMed: 10775529]
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[Full Text: https://doi.org/10.1086/302926]
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</p>
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<li>
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<p class="mim-text-font">
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Vache, C., Besnard, T., le Berre, P., Garcia-Garcia, G., Baux, D., Larrieu, L., Abadie, C., Blanchet, C., Bolz, H. J., Millan, J., Hamel, C., Malcolm, S., Claustres, M., Roux, A.-F.
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<strong>Usher syndrome type 2 caused by activation of an USH2A pseudoexon: implications for diagnosis and therapy.</strong>
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Hum. Mutat. 33: 104-108, 2012.
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van Wijk, E., Kersten, F. F. J., Kartono, A., Mans, D. A., Brandwijk, K., Letteboer, S. J. F., Peters, T. A., Marker, T., Yan, X., Cremers, C. W. R. J., Cremers, F. P. M., Wolfrum, U., Roepman, R., Kremer, H.
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<strong>Usher syndrome and Leber congenital amaurosis are molecularly linked via a novel isoform of the centrosomal ninein-like protein.</strong>
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Hum. Molec. Genet. 18: 51-64, 2009.
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van Wijk, E., Pennings, R. J. E., te Brinke, H., Claassen, A., Yntema, H. G., Hoefsloot, L. H., Cremers, F. P. M., Cremers, C. W. R. J., Kremer, H.
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<strong>Identification of 51 novel exons of the Usher syndrome type 2A (USH2A) gene that encode multiple conserved functional domains and that are mutated in patients with Usher syndrome type II.</strong>
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Am. J. Hum. Genet. 74: 738-744, 2004.
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Weston, M. D., Eudy, J. D., Fujita, S., Yao, S.-F., Usami, S., Cremers, C., Greenburg, J., Ramesar, R., Martini, A., Moller, C., Smith, R. J., Sumegi, J., Kimberling, W. J.
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<strong>Genomic structure and identification of novel mutations in usherin, the gene responsible for Usher syndrome type IIa.</strong>
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Am. J. Hum. Genet. 66: 1199-1210, 2000. Note: Erratum: Am. J. Hum. Genet. 66: 2020 only, 2000.
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Yan, D., Ouyang, X., Patterson, D. M., Du, L. L., Jacobson, S. G., Liu, X.-Z.
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<strong>Mutation analysis in the long isoform of USH2A in American patients with Usher syndrome type II.</strong>
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[PubMed: 19881469]
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Zlotogora, J.
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<strong>Parents of children with autosomal recessive diseases are not always carriers of the respective mutant alleles.</strong>
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Hum. Genet. 114: 521-526, 2004.
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[PubMed: 15024643]
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[Full Text: https://doi.org/10.1007/s00439-004-1105-y]
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Marla J. F. O'Neill - updated : 02/02/2023<br>Anne M. Lopez - updated : 10/11/2018<br>Nara Sobreira - updated : 11/10/2015<br>Marla J. F. O'Neill - updated : 6/11/2015<br>Cassandra L. Kniffin - updated : 1/9/2012<br>Marla J. F. O'Neill - updated : 5/3/2011<br>Cassandra L. Kniffin - updated : 6/14/2010<br>George E. Tiller - updated : 10/23/2009<br>George E. Tiller - updated : 7/20/2009<br>George E. Tiller - updated : 7/6/2009<br>Cassandra L. Kniffin - updated : 4/2/2009<br>Jane Kelly - updated : 11/30/2007<br>Cassandra L. Kniffin - updated : 10/10/2007<br>Patricia A. Hartz - updated : 4/30/2007<br>Cassandra L. Kniffin - updated : 12/28/2006<br>Marla J. F. O'Neill - updated : 3/13/2006<br>Marla J. F. O'Neill - updated : 6/2/2004<br>Victor A. McKusick - updated : 5/7/2004<br>Victor A. McKusick - updated : 4/22/2004<br>Victor A. McKusick - updated : 4/8/2004
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Cassandra L. Kniffin : 1/15/2004
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