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<title>
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Entry
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- *300039 - POU DOMAIN, CLASS 3, TRANSCRIPTION FACTOR 4; POU3F4
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- OMIM
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</ul>
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</div>
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</nav>
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<div id="mimSearch" class="hidden-print">
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<div class="container">
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<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchStart" name="start" value="1" />
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<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
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<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
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<div class="row">
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<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
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<div class="form-group">
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<div class="input-group">
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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<div class="input-group-btn">
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<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
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<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
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<ul class="dropdown-menu dropdown-menu-right">
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<li class="dropdown-header">
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Advanced Search
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/entry"> OMIM </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/geneMap"> Gene Map </a>
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<li role="separator" class="divider"></li>
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<li>
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<a href="/history"> Search History </a>
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</li>
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</ul>
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</div>
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</div>
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<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
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</div>
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</div>
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<div class="col-lg-4 col-md-4 col-sm-4 col-xs-4">
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<span class="small">
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</form>
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<p />
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</div>
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<div class="container hidden-print">
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<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
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<div id="mimAlertBanner">
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</div>
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</div>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*300039</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>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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</li>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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</li>
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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>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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</li>
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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>
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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>
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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/300039">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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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">
|
|
<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=ENSG00000196767;t=ENST00000644024" 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=5456" 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=300039" 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=ENSG00000196767;t=ENST00000644024" 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_000307" 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_000307" 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=300039" 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=02076&isoform_id=02076_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/POU3F4" 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/732756,77416874,119618983,189054618,433288480" 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/P49335" 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=5456" 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=ENSG00000196767;t=ENST00000644024" 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=POU3F4" 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=POU3F4" 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+5456" 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/POU3F4" 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:5456" 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/5456" 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=chrX&hgg_gene=ENST00000644024.2&hgg_start=83508290&hgg_end=83512127&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">
|
|
<div style="display: table-row">
|
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:9217" 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/pou3f4" 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=300039[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=300039[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/POU3F4/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/ENSG00000196767" 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.gwascentral.org/search?q=POU3F4" 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=POU3F4" 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://webh01.ua.ac.be/hhh/" title="Hereditary Hearing Loss Homepage" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Hereditary Hearing Loss Ho…</a></div><div style="margin-left: 0.5em;"><a href="http://www.LOVD.nl/POU3F4" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">POU3F4 database at LOVD</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=POU3F4&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/PA33541" 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:9217" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0086680.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:101894" 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/POU3F4#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:101894" 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/5456/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=5456" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00000431;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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</div>
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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=POU3F4&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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300039
|
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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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POU DOMAIN, CLASS 3, TRANSCRIPTION FACTOR 4; POU3F4
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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>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
BRAIN-4; BRN4
|
|
</span>
|
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</h4>
|
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</div>
|
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</div>
|
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=POU3F4" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">POU3F4</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/X/465?start=-3&limit=10&highlight=465">Xq21.1</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chrX:83508290-83512127&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'})">X:83,508,290-83,512,127</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
|
|
|
|
|
</span>
|
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</p>
|
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</div>
|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
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|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/X/465?start=-3&limit=10&highlight=465">
|
|
Xq21.1
|
|
</a>
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<p>The POU3F4 gene encodes a transcription factor that restricts the proliferation and lineage potential of neural stem cells (summary by <a href="#2" class="mim-tip-reference" title="Choi, B. Y., Kim, D.-H., Chung, T., Chang, M., Kim, E.-H., Kim, A. R., Seok, J., Chang, S. O., Bok, J., Kim, D., Oh, S.-H., Park, W.-Y. <strong>Destabilization and mislocalization of POU3F4 by C-terminal frameshift truncation and extension mutation.</strong> Hum. Mutat. 34: 309-316, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23076972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23076972</a>] [<a href="https://doi.org/10.1002/humu.22232" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23076972">Choi et al., 2013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23076972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#6" class="mim-tip-reference" title="de Kok, Y. J. M., van der Maarel, S. M., Bitner-Glindzicz, M., Huber, I., Monaco, A. P., Malcolm, S., Pembrey, M. E., Ropers, H.-H., Cremers, F. P. M. <strong>Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4.</strong> Science 267: 685-688, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7839145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7839145</a>] [<a href="https://doi.org/10.1126/science.7839145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7839145">De Kok et al. (1995)</a> used PCR primers complementary to the murine gene sequences to amplify a human POU3F4 fragment from cosmid DNA, which was then used as a probe to screen a human fetal brain cDNA library. They isolated 1.4 kb of the human POU3F4 cDNA sequence, which contained the complete 1,083-bp protein coding region. The rat and mouse proteins are completely identical, and the human protein contains only 4 conservative amino acid substitutions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7839145" 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="#7" class="mim-tip-reference" title="Douville, P. J., Atanasoski, S., Tobler, A., Fontana, A., Schwab, M. E. <strong>The brain-specific POU-box gene Brn4 is a sex-linked transcription factor located on the human and mouse X chromosomes.</strong> Mammalian Genome 5: 180-182, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7911044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7911044</a>] [<a href="https://doi.org/10.1007/BF00352353" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7911044">Douville et al. (1994)</a> showed that the rat homolog of POU3F4, called RHS2, is expressed during embryonic development in the brain, the neural tube, and the otic vesicle at 15.5 and 17.5 days after conception. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7911044" 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="#7" class="mim-tip-reference" title="Douville, P. J., Atanasoski, S., Tobler, A., Fontana, A., Schwab, M. E. <strong>The brain-specific POU-box gene Brn4 is a sex-linked transcription factor located on the human and mouse X chromosomes.</strong> Mammalian Genome 5: 180-182, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7911044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7911044</a>] [<a href="https://doi.org/10.1007/BF00352353" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7911044">Douville et al. (1994)</a> demonstrated that the mouse gene for Brain-4 (Pou3f4), which encodes a transcription factor, maps between the proteolipid protein locus Plp (<a href="/entry/300401">300401</a>) and the DXMit6 marker near the phosphoglycerate kinase-1 locus (Pgk1; <a href="/entry/311800">311800</a>). The chromosomal region between Pgk1 and Plp is evolutionarily conserved between humans and mice, which suggested that the human POU3F4 gene is located in the Xq13-q22 interval. <a href="#7" class="mim-tip-reference" title="Douville, P. J., Atanasoski, S., Tobler, A., Fontana, A., Schwab, M. E. <strong>The brain-specific POU-box gene Brn4 is a sex-linked transcription factor located on the human and mouse X chromosomes.</strong> Mammalian Genome 5: 180-182, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7911044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7911044</a>] [<a href="https://doi.org/10.1007/BF00352353" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7911044">Douville et al. (1994)</a> suggested that both its mapped position and its temporal/spatial expression pattern in early embryogenesis rendered POU3F4 an attractive candidate gene for the DFN3 locus (DFNX2; <a href="/entry/304400">304400</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7911044" 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 confirm and refine the localization of the human gene, <a href="#6" class="mim-tip-reference" title="de Kok, Y. J. M., van der Maarel, S. M., Bitner-Glindzicz, M., Huber, I., Monaco, A. P., Malcolm, S., Pembrey, M. E., Ropers, H.-H., Cremers, F. P. M. <strong>Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4.</strong> Science 267: 685-688, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7839145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7839145</a>] [<a href="https://doi.org/10.1126/science.7839145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7839145">de Kok et al. (1995)</a> amplified a murine genomic Pou3f4 gene fragment by PCR and hybridized it to Southern blots containing EcoRI-digested DNA from patients with Xq21 deletions. Hybridization was seen in the male control but not in DFN3 patients who carried variably sized deletions in Xq21. By hybridizing the probes to cosmids from a contig that spanned the DFN3 locus, they localized the POU3F4 gene 20 kb distal to DXS995. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7839145" 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 4 of 6 patients with X-linked mixed deafness (see DFNX2, <a href="/entry/304400">304400</a>), <a href="#6" class="mim-tip-reference" title="de Kok, Y. J. M., van der Maarel, S. M., Bitner-Glindzicz, M., Huber, I., Monaco, A. P., Malcolm, S., Pembrey, M. E., Ropers, H.-H., Cremers, F. P. M. <strong>Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4.</strong> Science 267: 685-688, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7839145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7839145</a>] [<a href="https://doi.org/10.1126/science.7839145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7839145">de Kok et al. (1995)</a> demonstrated a point mutation; in a fifth patient, in whom profound sensorineural deafness masked the conductive element of DFN3, a nonsense mutation was found (<a href="#0001">300039.0001</a>-<a href="#0005">300039.0005</a>). Unexpectedly, <a href="#6" class="mim-tip-reference" title="de Kok, Y. J. M., van der Maarel, S. M., Bitner-Glindzicz, M., Huber, I., Monaco, A. P., Malcolm, S., Pembrey, M. E., Ropers, H.-H., Cremers, F. P. M. <strong>Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4.</strong> Science 267: 685-688, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7839145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7839145</a>] [<a href="https://doi.org/10.1126/science.7839145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7839145">de Kok et al. (1995)</a> found that 3 Xq21 microdeletions and 1 duplication that had been identified previously in patients with DFN3 did not encompass the POU3F4 gene. In all 4 instances, the rearrangement was located proximal and 5-prime to POU3F4, with physical distances varying between 15 and 400 kb. In none of these patients, nor in 2 others with either a perilymphatic gusher during stapes surgery or a temporal bone defect, were point mutations detected in the POU3F4 gene. <a href="#6" class="mim-tip-reference" title="de Kok, Y. J. M., van der Maarel, S. M., Bitner-Glindzicz, M., Huber, I., Monaco, A. P., Malcolm, S., Pembrey, M. E., Ropers, H.-H., Cremers, F. P. M. <strong>Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4.</strong> Science 267: 685-688, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7839145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7839145</a>] [<a href="https://doi.org/10.1126/science.7839145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7839145">De Kok et al. (1995)</a> concluded that these cases may be caused by mutations that affect 5-prime noncoding or regulatory sequences. Alternatively, these aberrations may affect the gross chromosomal structure and thus affect expression of POU3F4. A less likely explanation might be the presence of other genes in Xq21.1 that can cause DFN3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7839145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Bitner-Glindzicz, M., Turnpenny, P., Hoglund, P., Kaariainen, H., Sankila, E.-M., van der Maarel, S. M., de Kok, Y. J. M., Ropers, H.-H., Cremers, F. P. M., Pembrey, M., Malcolm, S. <strong>Further mutations in brain 4 (POU3F4) clarify the phenotype in the X-linked deafness, DFN3.</strong> Hum. Molec. Genet. 4: 1467-1469, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581392</a>] [<a href="https://doi.org/10.1093/hmg/4.8.1467" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7581392">Bitner-Glindzicz et al. (1995)</a> described specific mutations in the POU3F4 gene in 2 families with X-linked deafness and suggested that the experience further clarifies the phenotype of DFN3. They concluded that DFN3 is characterized, not by mixed conductive and sensorineural deafness associated with perilymphatic gusher at stapes surgery, but by profound sensorineural deafness with or without a conductive component associated with a unique developmental abnormality of the ear. Their family 1 consisted of a mother and 2 sons of Finnish origin. The proband had mixed hearing loss of 40-50 dB and his brother a loss of 75-95 dB. The first brother was found to have a perilymphatic gusher at the time of stapedectomy. Sequencing of the product of PCR/SSCP revealed a 4-bp deletion at bases 862-866 of their clone, located in the homeodomain of the POU3F4 gene (<a href="#0006">300039.0006</a>). Family 2 was a British family with 3 affected males. All affected males had profound sensorineural deafness diagnosed in infancy with no suggestion of a conductive component. Although 2 were of normal intelligence, 1 had a moderately severe learning difficulty of unknown cause. On high resolution CT scanning of the cochlea performed in 1 of the males, the characteristic deficiency of bone between the basal turn of the cochlea and the internal auditory meatus was found. In studies of 4 generations of a family, the origin of the mutation in a heterozygous grandmother could be identified, the mutation being a C-to-T transition at nucleotide 935 resulting in an alanine to valine substitution in a highly conserved residue of the homeodomain of the predicted protein (<a href="#0007">300039.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7581392" 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>From observations of DFN3 in association with a complex duplication/paracentric inversion, <a href="#5" class="mim-tip-reference" title="de Kok, Y. J. M., Merkx, G. F. M., van der Maarel, S. M., Huber, I., Malcolm, S., Ropers, H.-H., Cremers, F. P. M. <strong>A duplication/paracentric inversion associated with familial X-linked deafness (DFN3) suggests the presence of a regulatory element more than 400 kb upstream of the POU3F4 gene.</strong> Hum. Molec. Genet. 4: 2145-2150, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8589693/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8589693</a>] [<a href="https://doi.org/10.1093/hmg/4.11.2145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8589693">de Kok et al. (1995)</a> concluded that there is a regulatory element located at least 400 kb upstream of the POU3F4 gene and that this was disconnected from the POU3F4 gene by the inversion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8589693" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The work of <a href="#5" class="mim-tip-reference" title="de Kok, Y. J. M., Merkx, G. F. M., van der Maarel, S. M., Huber, I., Malcolm, S., Ropers, H.-H., Cremers, F. P. M. <strong>A duplication/paracentric inversion associated with familial X-linked deafness (DFN3) suggests the presence of a regulatory element more than 400 kb upstream of the POU3F4 gene.</strong> Hum. Molec. Genet. 4: 2145-2150, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8589693/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8589693</a>] [<a href="https://doi.org/10.1093/hmg/4.11.2145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8589693">de Kok et al. (1995)</a> and of <a href="#1" class="mim-tip-reference" title="Bitner-Glindzicz, M., Turnpenny, P., Hoglund, P., Kaariainen, H., Sankila, E.-M., van der Maarel, S. M., de Kok, Y. J. M., Ropers, H.-H., Cremers, F. P. M., Pembrey, M., Malcolm, S. <strong>Further mutations in brain 4 (POU3F4) clarify the phenotype in the X-linked deafness, DFN3.</strong> Hum. Molec. Genet. 4: 1467-1469, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581392</a>] [<a href="https://doi.org/10.1093/hmg/4.8.1467" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7581392">Bitner-Glindzicz et al. (1995)</a> indicated that both mixed and pure sensorineural deafness may be caused by mutations in the POU3F4 gene and that they share the same radiologic phenotype as described by <a href="#10" class="mim-tip-reference" title="Phelps, P. D., Reardon, W., Pembrey, M., Bellman, S., Luxom, L. <strong>X-linked deafness, stapes gushers and a distinctive defect of the inner ear.</strong> Neuroradiology 33: 326-330, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1922747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1922747</a>] [<a href="https://doi.org/10.1007/BF00587816" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1922747">Phelps et al. (1991)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1922747+8589693+7581392" 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="Friedman, R. A., Bykhovskaya, Y., Tu, G., Talbot, J. M., Wilson, D. F., Parnes, L. S., Fischel-Ghodsian, N. <strong>Molecular analysis of the POU3F4 gene in patients with clinical and radiographic evidence of X-linked mixed deafness with perilymphatic gusher.</strong> Ann. Otol. Rhinol. Laryng. 106: 320-325, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9109724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9109724</a>] [<a href="https://doi.org/10.1177/000348949710600411" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9109724">Friedman et al. (1997)</a> found a novel mutation in the POU3F4 gene in 2 of 5 patients with X-linked mixed deafness studied. Although the clinical histories and radiographic abnormalities were characteristic in the other 3 patients, no mutation was identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9109724" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 unrelated patients with semicircular canal dehiscence and no family history of the disorder or of deafness, <a href="#3" class="mim-tip-reference" title="Crovetto, M. A., Whyte, J., Sarasola, E., Rodriguez, J. A., Garcia-Barcina, M. J. <strong>Absence of COCH gene mutations in patients with superior semicircular canal dehiscence. (Letter)</strong> Am. J. Med. Genet. 158A: 251-253, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22139968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22139968</a>] [<a href="https://doi.org/10.1002/ajmg.a.34377" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22139968">Crovetto et al. (2012)</a> excluded mutations in the coding exon of the POU3F4 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22139968" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 6 Korean families with X-linked deafness, <a href="#2" class="mim-tip-reference" title="Choi, B. Y., Kim, D.-H., Chung, T., Chang, M., Kim, E.-H., Kim, A. R., Seok, J., Chang, S. O., Bok, J., Kim, D., Oh, S.-H., Park, W.-Y. <strong>Destabilization and mislocalization of POU3F4 by C-terminal frameshift truncation and extension mutation.</strong> Hum. Mutat. 34: 309-316, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23076972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23076972</a>] [<a href="https://doi.org/10.1002/humu.22232" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23076972">Choi et al. (2013)</a> identified 6 pathogenic POU3F4 mutations, including 5 novel mutations (see, e.g., <a href="#0010">300039.0010</a> and <a href="#0011">300039.0011</a>). There were 2 missense mutations, 2 truncating mutations, and 2 mutations causing extension of the protein into the 3-prime untranslated region outside of the POU and NLS domains. All mutations resulted in decreased transcriptional activity of POU3F4 in cellular expression studies. The extension mutations were localized to the cytoplasm and underwent proteasomal degradation due to structural alterations. One of the frameshift mutations resulted in low protein levels that could be restored by a proteasome inhibitor, although transcriptional activity could not be restored to biologically meaningful levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23076972" 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>DFN3 (DFNX2; <a href="/entry/304400">304400</a>), an X chromosome-linked nonsyndromic mixed deafness, is caused by mutations in the BRN4 gene, which encodes a POU transcription factor. <a href="#9" class="mim-tip-reference" title="Minowa, O., Ikeda, K., Sugitani, Y., Oshima, T., Nakai, S., Katori, Y., Suzuki, M., Furukawa, M., Kawase, T., Zheng, Y., Ogura, M., Asada, Y., Watanabe, K., Yamanaka, H., Gotoh, S., Nishi-Takeshima, M., Sugimoto, T., Kikuchi, T., Takasaka, T., Noda, T. <strong>Altered cochlear fibrocytes in a mouse model of DFN3 nonsyndromic deafness.</strong> Science 285: 1408-1411, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10464101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10464101</a>] [<a href="https://doi.org/10.1126/science.285.5432.1408" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10464101">Minowa et al. (1999)</a> created Brn4-deficient mice. They had profound deafness. No gross morphologic changes were observed in the conductive ossicles or cochlea, although there was a dramatic reduction in endocochlear potential. Electron microscopy revealed severe ultrastructural alterations in cochlear spiral ligament fibrocytes. These findings suggested that these fibrocytes, which are mesenchymal in origin and for which a role in potassium ion homeostasis has been postulated, may play a critical role in auditory function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10464101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The phenotype of the mouse mutant 'sex-linked fidget' (slf) is caused by developmental malformations of the inner ear that results in hearing loss and vestibular dysfunction. Pilot mapping experiments suggested that the mouse Brn4 (human homolog, POU3F4) gene cosegregated with the slf locus on the mouse X chromosome. <a href="#11" class="mim-tip-reference" title="Phippard, D., Boyd, Y., Reed, V., Fisher, G., Masson, W. K., Evans, E. P., Saunders, J. C., Crenshaw, E. B., III. <strong>The sex-linked fidget mutation abolishes Brn4/Pou3f4 gene expression in the embryonic inner ear.</strong> Hum. Molec. Genet. 9: 79-85, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10587581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10587581</a>] [<a href="https://doi.org/10.1093/hmg/9.1.79" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10587581">Phippard et al. (2000)</a> identified the nature of the slf mutation: an X chromosomal inversion with 1 breakpoint close to Brn4. This inversion selectively eliminates expression of the Brn4 gene in the developing inner ear but not in the neural tube. <a href="#11" class="mim-tip-reference" title="Phippard, D., Boyd, Y., Reed, V., Fisher, G., Masson, W. K., Evans, E. P., Saunders, J. C., Crenshaw, E. B., III. <strong>The sex-linked fidget mutation abolishes Brn4/Pou3f4 gene expression in the embryonic inner ear.</strong> Hum. Molec. Genet. 9: 79-85, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10587581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10587581</a>] [<a href="https://doi.org/10.1093/hmg/9.1.79" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10587581">Phippard et al. (2000)</a> suggested that the slf mutation is a good mouse model for the most prevalent form of X-linked congenital deafness in man, which is associated with mutations in the human Brn4 ortholog, POU3F4. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10587581" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a patient with X-linked mixed deafness (DFNX2; <a href="/entry/304400">304400</a>), <a href="#6" class="mim-tip-reference" title="de Kok, Y. J. M., van der Maarel, S. M., Bitner-Glindzicz, M., Huber, I., Monaco, A. P., Malcolm, S., Pembrey, M. E., Ropers, H.-H., Cremers, F. P. M. <strong>Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4.</strong> Science 267: 685-688, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7839145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7839145</a>] [<a href="https://doi.org/10.1126/science.7839145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7839145">de Kok et al. (1995)</a> found a leu298-to-ter nonsense mutation. Patient 3055 carried a deletion of an A nucleotide at position 895. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7839145" 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 patient 3105 with X-linked mixed deafness (DFNX2; <a href="/entry/304400">304400</a>), <a href="#6" class="mim-tip-reference" title="de Kok, Y. J. M., van der Maarel, S. M., Bitner-Glindzicz, M., Huber, I., Monaco, A. P., Malcolm, S., Pembrey, M. E., Ropers, H.-H., Cremers, F. P. M. <strong>Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4.</strong> Science 267: 685-688, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7839145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7839145</a>] [<a href="https://doi.org/10.1126/science.7839145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7839145">de Kok et al. (1995)</a> found a deletion of 1 guanine that is part of a GGGG tetranucleotide stretch at positions 648 to 651, resulting in conversion of asp215 to a stop codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7839145" 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">rs104894920 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894920;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=rs104894920" 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=rs104894920" 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=RCV000012444" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012444" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012444</a>
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<p>In a family studied earlier by <a href="#12" class="mim-tip-reference" title="Reardon, W., Middleton-Price, H. R., Sandkuijl, L., Phelps, P., Bellman, S., Luxon, L., Pembrey, M. E., Malcolm, S. <strong>A multipedigree linkage study of X-linked deafness: linkage to Xq13-q21 and evidence for genetic heterogeneity.</strong> Genomics 11: 885-894, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1783396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1783396</a>] [<a href="https://doi.org/10.1016/0888-7543(91)90011-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1783396">Reardon et al. (1991)</a>, <a href="#6" class="mim-tip-reference" title="de Kok, Y. J. M., van der Maarel, S. M., Bitner-Glindzicz, M., Huber, I., Monaco, A. P., Malcolm, S., Pembrey, M. E., Ropers, H.-H., Cremers, F. P. M. <strong>Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4.</strong> Science 267: 685-688, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7839145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7839145</a>] [<a href="https://doi.org/10.1126/science.7839145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7839145">de Kok et al. (1995)</a> found deletion of a CAAA tetranucleotide that is present in tandem at positions 603 to 610 of the wildtype POU3F4 sequence. They were able to show that the mutation cosegregated with the DFN3 phenotype in the whole family. The phenotype in this family was dominated by profound sensorineural deafness that masked the conductive element usually seen with DFN3 (DFNX2; <a href="/entry/304400">304400</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1783396+7839145" 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">rs104894921 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894921;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=rs104894921" 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=rs104894921" 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=RCV000012445" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012445" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012445</a>
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<p>In patient 5736 with X-linked mixed deafness (DFNX2; <a href="/entry/304400">304400</a>), <a href="#6" class="mim-tip-reference" title="de Kok, Y. J. M., van der Maarel, S. M., Bitner-Glindzicz, M., Huber, I., Monaco, A. P., Malcolm, S., Pembrey, M. E., Ropers, H.-H., Cremers, F. P. M. <strong>Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4.</strong> Science 267: 685-688, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7839145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7839145</a>] [<a href="https://doi.org/10.1126/science.7839145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7839145">de Kok et al. (1995)</a> found a leu317-to-trp mutation in the POU3F4 gene. The leucine residue at position 317 is located between helices 2 and 3 of the POU homeodomain, as deduced from nuclear magnetic resonance and crystallographic studies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7839145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 DEAFNESS, X-LINKED 2</strong>
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POU3F4, LYS334GLU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894922 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894922;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=rs104894922" 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=rs104894922" 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=RCV000012446" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012446" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012446</a>
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<p>In a family with X-linked mixed deafness (DFNX2; <a href="/entry/304400">304400</a>), <a href="#6" class="mim-tip-reference" title="de Kok, Y. J. M., van der Maarel, S. M., Bitner-Glindzicz, M., Huber, I., Monaco, A. P., Malcolm, S., Pembrey, M. E., Ropers, H.-H., Cremers, F. P. M. <strong>Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4.</strong> Science 267: 685-688, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7839145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7839145</a>] [<a href="https://doi.org/10.1126/science.7839145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7839145">de Kok et al. (1995)</a> found a nonconservative K334E substitution in the POU homeodomain of the POU3F4 protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7839145" 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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POU3F4, 4-BP DEL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs730882189 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs730882189;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=rs730882189" 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=rs730882189" 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=RCV000012447" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012447" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012447</a>
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<p>In 2 brothers with mixed hearing loss and established perilymphatic gusher (DFNX2; <a href="/entry/304400">304400</a>) in 1 and in their asymptomatic mother, <a href="#1" class="mim-tip-reference" title="Bitner-Glindzicz, M., Turnpenny, P., Hoglund, P., Kaariainen, H., Sankila, E.-M., van der Maarel, S. M., de Kok, Y. J. M., Ropers, H.-H., Cremers, F. P. M., Pembrey, M., Malcolm, S. <strong>Further mutations in brain 4 (POU3F4) clarify the phenotype in the X-linked deafness, DFN3.</strong> Hum. Molec. Genet. 4: 1467-1469, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581392</a>] [<a href="https://doi.org/10.1093/hmg/4.8.1467" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7581392">Bitner-Glindzicz et al. (1995)</a> demonstrated a 4-bp deletion at bases 862-866 of their clone located in the homeodomain which resulted in a frameshift. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7581392" 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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POU3F4, 935C-T, ALA-VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906502 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906502;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=rs387906502" 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=rs387906502" 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=RCV000012448" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012448" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012448</a>
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<p>In a British family in which 2 brothers and their maternal uncle had profound sensorineural deafness 'diagnosed in infancy with no suggestion of a conductive component' (DFNX2; <a href="/entry/304400">304400</a>) and in the asymptomatic maternal grandmother, <a href="#1" class="mim-tip-reference" title="Bitner-Glindzicz, M., Turnpenny, P., Hoglund, P., Kaariainen, H., Sankila, E.-M., van der Maarel, S. M., de Kok, Y. J. M., Ropers, H.-H., Cremers, F. P. M., Pembrey, M., Malcolm, S. <strong>Further mutations in brain 4 (POU3F4) clarify the phenotype in the X-linked deafness, DFN3.</strong> Hum. Molec. Genet. 4: 1467-1469, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581392</a>] [<a href="https://doi.org/10.1093/hmg/4.8.1467" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7581392">Bitner-Glindzicz et al. (1995)</a> identified a C-to-T transition at nucleotide 935 of the POU3F4 gene resulting in an alanine to valine substitution in a highly conserved residue of the homeodomain of the predicted protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7581392" 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">rs104894923 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894923;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=rs104894923" 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=rs104894923" 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=RCV000012449" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012449" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012449</a>
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<p>In a patient with X-linked mixed deafness (DFNX2; <a href="/entry/304400">304400</a>), <a href="#4" class="mim-tip-reference" title="de Kok, Y. J. M., Cremers, C. W. R. J., Ropers, H.-H., Cremers, F. P. M. <strong>The molecular basis of X-linked deafness type 3 (DFN3) in two sporadic cases: identification of a somatic mosaicism for a POU3F4 missense mutation.</strong> Hum. Mutat. 10: 207-211, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9298820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9298820</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1997)10:3<207::AID-HUMU5>3.0.CO;2-F" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9298820">de Kok et al. (1997)</a> found a mutation in the POU3F4 gene predicted to result in an arg330-to-ser amino acid substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9298820" 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">rs104894924 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894924;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=rs104894924" 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=rs104894924" 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=RCV000012450" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012450" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012450</a>
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<p>In a patient with X-linked mixed deafness (DFNX2; <a href="/entry/304400">304400</a>), <a href="#4" class="mim-tip-reference" title="de Kok, Y. J. M., Cremers, C. W. R. J., Ropers, H.-H., Cremers, F. P. M. <strong>The molecular basis of X-linked deafness type 3 (DFN3) in two sporadic cases: identification of a somatic mosaicism for a POU3F4 missense mutation.</strong> Hum. Mutat. 10: 207-211, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9298820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9298820</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1997)10:3<207::AID-HUMU5>3.0.CO;2-F" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9298820">de Kok et al. (1997)</a> found somatic mosaicism for an arg323-to-gly amino acid substitution in the POU3F4 gene. The mosaicism was detected in 2 independently established EBV immortalized B cells and peripheral blood lymphocytes (PBLs). Semiquantitative analysis showed that approximately 50% of the PBLs of this patient carried the mutation. The arg323-to-gly mutation appears to have occurred very early in embryogenesis, before the differentiation of cells involved in hematopoiesis and inner ear development. The mutation was situated in the POU homeodomain and was predicted to disrupt the DNA binding of the POU3F4 protein. All previously described point mutations had been found in the POU domains of POU3F4. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9298820" 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">rs398122517 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398122517;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=rs398122517" 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=rs398122517" 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=RCV000034344" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000034344" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000034344</a>
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<p>In 2 affected brothers of a Korean family segregating X-linked mixed deafness (DFNX2; <a href="/entry/304400">304400</a>), <a href="#2" class="mim-tip-reference" title="Choi, B. Y., Kim, D.-H., Chung, T., Chang, M., Kim, E.-H., Kim, A. R., Seok, J., Chang, S. O., Bok, J., Kim, D., Oh, S.-H., Park, W.-Y. <strong>Destabilization and mislocalization of POU3F4 by C-terminal frameshift truncation and extension mutation.</strong> Hum. Mutat. 34: 309-316, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23076972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23076972</a>] [<a href="https://doi.org/10.1002/humu.22232" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23076972">Choi et al. (2013)</a> identified a 1-bp deletion (1069delA) in the POU3F4 gene, resulting in a frameshift and extension of the translated protein into the 3-prime untranslated region (Thr354GlnfsTer115). The mutation was not found in 100 controls or in a large exome sequence database. Transfection of the mutation into HEK293 cells resulted in normal levels of mutant transcript, but decreased levels of protein compared to controls, suggesting that the mutation alters protein stability. The mutant protein also showed abnormal intracellular localization, with most of the protein located in the cytoplasm and not in the nucleus. The mutant protein showed decreased transcriptional activity compared to wildtype. <a href="#2" class="mim-tip-reference" title="Choi, B. Y., Kim, D.-H., Chung, T., Chang, M., Kim, E.-H., Kim, A. R., Seok, J., Chang, S. O., Bok, J., Kim, D., Oh, S.-H., Park, W.-Y. <strong>Destabilization and mislocalization of POU3F4 by C-terminal frameshift truncation and extension mutation.</strong> Hum. Mutat. 34: 309-316, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23076972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23076972</a>] [<a href="https://doi.org/10.1002/humu.22232" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23076972">Choi et al. (2013)</a> concluded that this frameshift extension mutation limited accessibility of the mutant protein to the cis-acting regulatory sequences of POU3F4 target genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23076972" 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">rs398122516 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398122516;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=rs398122516" 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=rs398122516" 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=RCV000034343" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000034343" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000034343</a>
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<p>In a Korean proband and his maternal uncle with X-linked deafness (DFNX2; <a href="/entry/304400">304400</a>), <a href="#2" class="mim-tip-reference" title="Choi, B. Y., Kim, D.-H., Chung, T., Chang, M., Kim, E.-H., Kim, A. R., Seok, J., Chang, S. O., Bok, J., Kim, D., Oh, S.-H., Park, W.-Y. <strong>Destabilization and mislocalization of POU3F4 by C-terminal frameshift truncation and extension mutation.</strong> Hum. Mutat. 34: 309-316, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23076972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23076972</a>] [<a href="https://doi.org/10.1002/humu.22232" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23076972">Choi et al. (2013)</a> identified a 1-bp duplication (950dupT) in the POU3F4 gene, resulting in a frameshift and premature termination (Leu317PhefsTer12) of the C-terminal 44 residues spanning the POU domain and the NLS. The mutation was not found in 100 controls or in a large exome sequence database. Transfection of the mutation into HEK293 cells resulted in normal levels of mutant transcript, but decreased levels of protein compared to controls. The mutant protein localized to both the nucleus and the cytoplasm. Treatment with a proteasome inhibitor (MG132) resulted in an increase in protein levels and a small increase in transcriptional activity, but not restoration to wildtype levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23076972" 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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Bitner-Glindzicz, M., Turnpenny, P., Hoglund, P., Kaariainen, H., Sankila, E.-M., van der Maarel, S. M., de Kok, Y. J. M., Ropers, H.-H., Cremers, F. P. M., Pembrey, M., Malcolm, S.
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<strong>Further mutations in brain 4 (POU3F4) clarify the phenotype in the X-linked deafness, DFN3.</strong>
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Hum. Molec. Genet. 4: 1467-1469, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581392</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7581392" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Choi, B. Y., Kim, D.-H., Chung, T., Chang, M., Kim, E.-H., Kim, A. R., Seok, J., Chang, S. O., Bok, J., Kim, D., Oh, S.-H., Park, W.-Y.
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<strong>Destabilization and mislocalization of POU3F4 by C-terminal frameshift truncation and extension mutation.</strong>
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Hum. Mutat. 34: 309-316, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23076972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23076972</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23076972" 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.22232" target="_blank">Full Text</a>]
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Crovetto, M. A., Whyte, J., Sarasola, E., Rodriguez, J. A., Garcia-Barcina, M. J.
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<strong>Absence of COCH gene mutations in patients with superior semicircular canal dehiscence. (Letter)</strong>
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Am. J. Med. Genet. 158A: 251-253, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22139968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22139968</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22139968" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<strong>The molecular basis of X-linked deafness type 3 (DFN3) in two sporadic cases: identification of a somatic mosaicism for a POU3F4 missense mutation.</strong>
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Hum. Mutat. 10: 207-211, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9298820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9298820</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9298820" 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/(SICI)1098-1004(1997)10:3<207::AID-HUMU5>3.0.CO;2-F" target="_blank">Full Text</a>]
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<strong>A duplication/paracentric inversion associated with familial X-linked deafness (DFN3) suggests the presence of a regulatory element more than 400 kb upstream of the POU3F4 gene.</strong>
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Hum. Molec. Genet. 4: 2145-2150, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8589693/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8589693</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8589693" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1093/hmg/4.11.2145" target="_blank">Full Text</a>]
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</p>
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|
</div>
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|
</li>
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<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="de Kok1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
de Kok, Y. J. M., van der Maarel, S. M., Bitner-Glindzicz, M., Huber, I., Monaco, A. P., Malcolm, S., Pembrey, M. E., Ropers, H.-H., Cremers, F. P. M.
|
|
<strong>Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4.</strong>
|
|
Science 267: 685-688, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7839145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7839145</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7839145" 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/10.1126/science.7839145" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="7" class="mim-anchor"></a>
|
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<a id="Douville1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Douville, P. J., Atanasoski, S., Tobler, A., Fontana, A., Schwab, M. E.
|
|
<strong>The brain-specific POU-box gene Brn4 is a sex-linked transcription factor located on the human and mouse X chromosomes.</strong>
|
|
Mammalian Genome 5: 180-182, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7911044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7911044</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7911044" 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/BF00352353" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Friedman1997" class="mim-anchor"></a>
|
|
<div class="">
|
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<p class="mim-text-font">
|
|
Friedman, R. A., Bykhovskaya, Y., Tu, G., Talbot, J. M., Wilson, D. F., Parnes, L. S., Fischel-Ghodsian, N.
|
|
<strong>Molecular analysis of the POU3F4 gene in patients with clinical and radiographic evidence of X-linked mixed deafness with perilymphatic gusher.</strong>
|
|
Ann. Otol. Rhinol. Laryng. 106: 320-325, 1997.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9109724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9109724</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9109724" 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/10.1177/000348949710600411" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Minowa1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Minowa, O., Ikeda, K., Sugitani, Y., Oshima, T., Nakai, S., Katori, Y., Suzuki, M., Furukawa, M., Kawase, T., Zheng, Y., Ogura, M., Asada, Y., Watanabe, K., Yamanaka, H., Gotoh, S., Nishi-Takeshima, M., Sugimoto, T., Kikuchi, T., Takasaka, T., Noda, T.
|
|
<strong>Altered cochlear fibrocytes in a mouse model of DFN3 nonsyndromic deafness.</strong>
|
|
Science 285: 1408-1411, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10464101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10464101</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10464101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1126/science.285.5432.1408" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Phelps1991" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
|
Phelps, P. D., Reardon, W., Pembrey, M., Bellman, S., Luxom, L.
|
|
<strong>X-linked deafness, stapes gushers and a distinctive defect of the inner ear.</strong>
|
|
Neuroradiology 33: 326-330, 1991.
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|
|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1922747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1922747</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1922747" 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/BF00587816" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Phippard2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
|
Phippard, D., Boyd, Y., Reed, V., Fisher, G., Masson, W. K., Evans, E. P., Saunders, J. C., Crenshaw, E. B., III.
|
|
<strong>The sex-linked fidget mutation abolishes Brn4/Pou3f4 gene expression in the embryonic inner ear.</strong>
|
|
Hum. Molec. Genet. 9: 79-85, 2000.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10587581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10587581</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10587581" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/9.1.79" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Reardon1991" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Reardon, W., Middleton-Price, H. R., Sandkuijl, L., Phelps, P., Bellman, S., Luxon, L., Pembrey, M. E., Malcolm, S.
|
|
<strong>A multipedigree linkage study of X-linked deafness: linkage to Xq13-q21 and evidence for genetic heterogeneity.</strong>
|
|
Genomics 11: 885-894, 1991.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1783396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1783396</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1783396" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
|
[<a href="https://doi.org/10.1016/0888-7543(91)90011-3" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
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</span>
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</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 3/27/2013
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</span>
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</div>
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</div>
|
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<div class="row collapse" id="mimCollapseContributors">
|
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 2/16/2012<br>Ada Hamosh - updated : 4/18/2001<br>Ada Hamosh - updated : 2/1/2000<br>Victor A. McKusick - updated : 10/10/1997<br>Victor A. McKusick - updated : 6/21/1997<br>Victor A. McKusick - updated : 3/6/1997
|
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
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<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
Victor A. McKusick : 3/12/1996
|
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
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<span class="text-nowrap mim-text-font">
|
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
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</span>
|
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</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 03/20/2023
|
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</span>
|
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</div>
|
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</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
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|
carol : 06/23/2016<br>carol : 3/3/2015<br>carol : 9/12/2013<br>carol : 4/1/2013<br>ckniffin : 3/27/2013<br>carol : 5/17/2012<br>ckniffin : 5/16/2012<br>carol : 2/16/2012<br>ckniffin : 2/16/2012<br>carol : 5/24/2011<br>carol : 4/16/2009<br>wwang : 3/18/2008<br>ckniffin : 8/28/2002<br>carol : 11/24/2001<br>alopez : 4/19/2001<br>terry : 4/18/2001<br>alopez : 2/2/2000<br>terry : 2/1/2000<br>jenny : 10/17/1997<br>terry : 10/10/1997<br>alopez : 7/10/1997<br>terry : 6/24/1997<br>terry : 6/21/1997<br>jenny : 3/6/1997<br>terry : 2/13/1997<br>joanna : 3/14/1996<br>mark : 3/14/1996
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
|
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<span class="mim-font">
|
|
<strong>*</strong> 300039
|
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</span>
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</h3>
|
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</div>
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<div>
|
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<h3>
|
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<span class="mim-font">
|
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|
|
POU DOMAIN, CLASS 3, TRANSCRIPTION FACTOR 4; POU3F4
|
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</span>
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</h3>
|
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
|
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
BRAIN-4; BRN4
|
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</span>
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: POU3F4</em></strong>
|
|
</span>
|
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</p>
|
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
|
<strong>
|
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<em>
|
|
Cytogenetic location: Xq21.1
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : X:83,508,290-83,512,127 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
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</p>
|
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</div>
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<div>
|
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<br />
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</h4>
|
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<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
Xq21.1
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Deafness, X-linked 2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
304400
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
X-linked recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
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|
<div>
|
|
<br />
|
|
</div>
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<div>
|
|
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
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|
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
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|
<span class="mim-text-font">
|
|
<p>The POU3F4 gene encodes a transcription factor that restricts the proliferation and lineage potential of neural stem cells (summary by Choi et al., 2013). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>De Kok et al. (1995) used PCR primers complementary to the murine gene sequences to amplify a human POU3F4 fragment from cosmid DNA, which was then used as a probe to screen a human fetal brain cDNA library. They isolated 1.4 kb of the human POU3F4 cDNA sequence, which contained the complete 1,083-bp protein coding region. The rat and mouse proteins are completely identical, and the human protein contains only 4 conservative amino acid substitutions. </p><p>Douville et al. (1994) showed that the rat homolog of POU3F4, called RHS2, is expressed during embryonic development in the brain, the neural tube, and the otic vesicle at 15.5 and 17.5 days after conception. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<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>Douville et al. (1994) demonstrated that the mouse gene for Brain-4 (Pou3f4), which encodes a transcription factor, maps between the proteolipid protein locus Plp (300401) and the DXMit6 marker near the phosphoglycerate kinase-1 locus (Pgk1; 311800). The chromosomal region between Pgk1 and Plp is evolutionarily conserved between humans and mice, which suggested that the human POU3F4 gene is located in the Xq13-q22 interval. Douville et al. (1994) suggested that both its mapped position and its temporal/spatial expression pattern in early embryogenesis rendered POU3F4 an attractive candidate gene for the DFN3 locus (DFNX2; 304400). </p><p>To confirm and refine the localization of the human gene, de Kok et al. (1995) amplified a murine genomic Pou3f4 gene fragment by PCR and hybridized it to Southern blots containing EcoRI-digested DNA from patients with Xq21 deletions. Hybridization was seen in the male control but not in DFN3 patients who carried variably sized deletions in Xq21. By hybridizing the probes to cosmids from a contig that spanned the DFN3 locus, they localized the POU3F4 gene 20 kb distal to DXS995. </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">
|
|
<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">
|
|
<p>In 4 of 6 patients with X-linked mixed deafness (see DFNX2, 304400), de Kok et al. (1995) demonstrated a point mutation; in a fifth patient, in whom profound sensorineural deafness masked the conductive element of DFN3, a nonsense mutation was found (300039.0001-300039.0005). Unexpectedly, de Kok et al. (1995) found that 3 Xq21 microdeletions and 1 duplication that had been identified previously in patients with DFN3 did not encompass the POU3F4 gene. In all 4 instances, the rearrangement was located proximal and 5-prime to POU3F4, with physical distances varying between 15 and 400 kb. In none of these patients, nor in 2 others with either a perilymphatic gusher during stapes surgery or a temporal bone defect, were point mutations detected in the POU3F4 gene. De Kok et al. (1995) concluded that these cases may be caused by mutations that affect 5-prime noncoding or regulatory sequences. Alternatively, these aberrations may affect the gross chromosomal structure and thus affect expression of POU3F4. A less likely explanation might be the presence of other genes in Xq21.1 that can cause DFN3. </p><p>Bitner-Glindzicz et al. (1995) described specific mutations in the POU3F4 gene in 2 families with X-linked deafness and suggested that the experience further clarifies the phenotype of DFN3. They concluded that DFN3 is characterized, not by mixed conductive and sensorineural deafness associated with perilymphatic gusher at stapes surgery, but by profound sensorineural deafness with or without a conductive component associated with a unique developmental abnormality of the ear. Their family 1 consisted of a mother and 2 sons of Finnish origin. The proband had mixed hearing loss of 40-50 dB and his brother a loss of 75-95 dB. The first brother was found to have a perilymphatic gusher at the time of stapedectomy. Sequencing of the product of PCR/SSCP revealed a 4-bp deletion at bases 862-866 of their clone, located in the homeodomain of the POU3F4 gene (300039.0006). Family 2 was a British family with 3 affected males. All affected males had profound sensorineural deafness diagnosed in infancy with no suggestion of a conductive component. Although 2 were of normal intelligence, 1 had a moderately severe learning difficulty of unknown cause. On high resolution CT scanning of the cochlea performed in 1 of the males, the characteristic deficiency of bone between the basal turn of the cochlea and the internal auditory meatus was found. In studies of 4 generations of a family, the origin of the mutation in a heterozygous grandmother could be identified, the mutation being a C-to-T transition at nucleotide 935 resulting in an alanine to valine substitution in a highly conserved residue of the homeodomain of the predicted protein (300039.0007). </p><p>From observations of DFN3 in association with a complex duplication/paracentric inversion, de Kok et al. (1995) concluded that there is a regulatory element located at least 400 kb upstream of the POU3F4 gene and that this was disconnected from the POU3F4 gene by the inversion. </p><p>The work of de Kok et al. (1995) and of Bitner-Glindzicz et al. (1995) indicated that both mixed and pure sensorineural deafness may be caused by mutations in the POU3F4 gene and that they share the same radiologic phenotype as described by Phelps et al. (1991). </p><p>Friedman et al. (1997) found a novel mutation in the POU3F4 gene in 2 of 5 patients with X-linked mixed deafness studied. Although the clinical histories and radiographic abnormalities were characteristic in the other 3 patients, no mutation was identified. </p><p>In 3 unrelated patients with semicircular canal dehiscence and no family history of the disorder or of deafness, Crovetto et al. (2012) excluded mutations in the coding exon of the POU3F4 gene. </p><p>In 6 Korean families with X-linked deafness, Choi et al. (2013) identified 6 pathogenic POU3F4 mutations, including 5 novel mutations (see, e.g., 300039.0010 and 300039.0011). There were 2 missense mutations, 2 truncating mutations, and 2 mutations causing extension of the protein into the 3-prime untranslated region outside of the POU and NLS domains. All mutations resulted in decreased transcriptional activity of POU3F4 in cellular expression studies. The extension mutations were localized to the cytoplasm and underwent proteasomal degradation due to structural alterations. One of the frameshift mutations resulted in low protein levels that could be restored by a proteasome inhibitor, although transcriptional activity could not be restored to biologically meaningful levels. </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">
|
|
<strong>Animal Model</strong>
|
|
</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
|
<p>DFN3 (DFNX2; 304400), an X chromosome-linked nonsyndromic mixed deafness, is caused by mutations in the BRN4 gene, which encodes a POU transcription factor. Minowa et al. (1999) created Brn4-deficient mice. They had profound deafness. No gross morphologic changes were observed in the conductive ossicles or cochlea, although there was a dramatic reduction in endocochlear potential. Electron microscopy revealed severe ultrastructural alterations in cochlear spiral ligament fibrocytes. These findings suggested that these fibrocytes, which are mesenchymal in origin and for which a role in potassium ion homeostasis has been postulated, may play a critical role in auditory function. </p><p>The phenotype of the mouse mutant 'sex-linked fidget' (slf) is caused by developmental malformations of the inner ear that results in hearing loss and vestibular dysfunction. Pilot mapping experiments suggested that the mouse Brn4 (human homolog, POU3F4) gene cosegregated with the slf locus on the mouse X chromosome. Phippard et al. (2000) identified the nature of the slf mutation: an X chromosomal inversion with 1 breakpoint close to Brn4. This inversion selectively eliminates expression of the Brn4 gene in the developing inner ear but not in the neural tube. Phippard et al. (2000) suggested that the slf mutation is a good mouse model for the most prevalent form of X-linked congenital deafness in man, which is associated with mutations in the human Brn4 ortholog, POU3F4. </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>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>11 Selected Examples):</strong>
|
|
</span>
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</h4>
|
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<div>
|
|
<p />
|
|
</div>
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<div>
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<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 DEAFNESS, X-LINKED 2</strong>
|
|
</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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POU3F4, LEU298TER
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<br />
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SNP: rs267606974,
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|
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ClinVar: RCV000144387
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with X-linked mixed deafness (DFNX2; 304400), de Kok et al. (1995) found a leu298-to-ter nonsense mutation. Patient 3055 carried a deletion of an A nucleotide at position 895. </p>
|
|
</span>
|
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</div>
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<div>
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<br />
|
|
</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 DEAFNESS, X-LINKED 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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|
|
POU3F4, ASP215TER
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<br />
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|
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SNP: rs1555984570,
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|
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ClinVar: RCV000012443
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</span>
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</div>
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In patient 3105 with X-linked mixed deafness (DFNX2; 304400), de Kok et al. (1995) found a deletion of 1 guanine that is part of a GGGG tetranucleotide stretch at positions 648 to 651, resulting in conversion of asp215 to a stop codon. </p>
|
|
</span>
|
|
</div>
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<div>
|
|
<br />
|
|
</div>
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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>.0003 DEAFNESS, X-LINKED 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
POU3F4, LYS202TER
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|
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|
|
<br />
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|
|
SNP: rs104894920,
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|
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|
|
ClinVar: RCV000012444
|
|
|
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|
|
</span>
|
|
</div>
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|
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|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family studied earlier by Reardon et al. (1991), de Kok et al. (1995) found deletion of a CAAA tetranucleotide that is present in tandem at positions 603 to 610 of the wildtype POU3F4 sequence. They were able to show that the mutation cosegregated with the DFN3 phenotype in the whole family. The phenotype in this family was dominated by profound sensorineural deafness that masked the conductive element usually seen with DFN3 (DFNX2; 304400). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 DEAFNESS, X-LINKED 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
POU3F4, LEU317TRP
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs104894921,
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|
|
|
|
|
|
|
ClinVar: RCV000012445
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In patient 5736 with X-linked mixed deafness (DFNX2; 304400), de Kok et al. (1995) found a leu317-to-trp mutation in the POU3F4 gene. The leucine residue at position 317 is located between helices 2 and 3 of the POU homeodomain, as deduced from nuclear magnetic resonance and crystallographic studies. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 DEAFNESS, X-LINKED 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
POU3F4, LYS334GLU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894922,
|
|
|
|
|
|
|
|
ClinVar: RCV000012446
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with X-linked mixed deafness (DFNX2; 304400), de Kok et al. (1995) found a nonconservative K334E substitution in the POU homeodomain of the POU3F4 protein. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 DEAFNESS, X-LINKED 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
POU3F4, 4-BP DEL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs730882189,
|
|
|
|
|
|
|
|
ClinVar: RCV000012447
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 brothers with mixed hearing loss and established perilymphatic gusher (DFNX2; 304400) in 1 and in their asymptomatic mother, Bitner-Glindzicz et al. (1995) demonstrated a 4-bp deletion at bases 862-866 of their clone located in the homeodomain which resulted in a frameshift. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 DEAFNESS, X-LINKED 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
POU3F4, 935C-T, ALA-VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906502,
|
|
|
|
|
|
|
|
ClinVar: RCV000012448
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a British family in which 2 brothers and their maternal uncle had profound sensorineural deafness 'diagnosed in infancy with no suggestion of a conductive component' (DFNX2; 304400) and in the asymptomatic maternal grandmother, Bitner-Glindzicz et al. (1995) identified a C-to-T transition at nucleotide 935 of the POU3F4 gene resulting in an alanine to valine substitution in a highly conserved residue of the homeodomain of the predicted protein. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 DEAFNESS, X-LINKED 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
POU3F4, ARG330SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894923,
|
|
|
|
|
|
|
|
ClinVar: RCV000012449
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with X-linked mixed deafness (DFNX2; 304400), de Kok et al. (1997) found a mutation in the POU3F4 gene predicted to result in an arg330-to-ser amino acid substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 DEAFNESS, X-LINKED 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
POU3F4, ARG323GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894924,
|
|
|
|
|
|
|
|
ClinVar: RCV000012450
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with X-linked mixed deafness (DFNX2; 304400), de Kok et al. (1997) found somatic mosaicism for an arg323-to-gly amino acid substitution in the POU3F4 gene. The mosaicism was detected in 2 independently established EBV immortalized B cells and peripheral blood lymphocytes (PBLs). Semiquantitative analysis showed that approximately 50% of the PBLs of this patient carried the mutation. The arg323-to-gly mutation appears to have occurred very early in embryogenesis, before the differentiation of cells involved in hematopoiesis and inner ear development. The mutation was situated in the POU homeodomain and was predicted to disrupt the DNA binding of the POU3F4 protein. All previously described point mutations had been found in the POU domains of POU3F4. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 DEAFNESS, X-LINKED 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
POU3F4, 1-BP DEL, 1069A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs398122517,
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|
|
|
|
|
|
|
ClinVar: RCV000034344
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 affected brothers of a Korean family segregating X-linked mixed deafness (DFNX2; 304400), Choi et al. (2013) identified a 1-bp deletion (1069delA) in the POU3F4 gene, resulting in a frameshift and extension of the translated protein into the 3-prime untranslated region (Thr354GlnfsTer115). The mutation was not found in 100 controls or in a large exome sequence database. Transfection of the mutation into HEK293 cells resulted in normal levels of mutant transcript, but decreased levels of protein compared to controls, suggesting that the mutation alters protein stability. The mutant protein also showed abnormal intracellular localization, with most of the protein located in the cytoplasm and not in the nucleus. The mutant protein showed decreased transcriptional activity compared to wildtype. Choi et al. (2013) concluded that this frameshift extension mutation limited accessibility of the mutant protein to the cis-acting regulatory sequences of POU3F4 target genes. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 DEAFNESS, X-LINKED 2</strong>
|
|
</span>
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POU3F4, 1-BP DUP, 950T
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<br />
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SNP: rs398122516,
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ClinVar: RCV000034343
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<p>In a Korean proband and his maternal uncle with X-linked deafness (DFNX2; 304400), Choi et al. (2013) identified a 1-bp duplication (950dupT) in the POU3F4 gene, resulting in a frameshift and premature termination (Leu317PhefsTer12) of the C-terminal 44 residues spanning the POU domain and the NLS. The mutation was not found in 100 controls or in a large exome sequence database. Transfection of the mutation into HEK293 cells resulted in normal levels of mutant transcript, but decreased levels of protein compared to controls. The mutant protein localized to both the nucleus and the cytoplasm. Treatment with a proteasome inhibitor (MG132) resulted in an increase in protein levels and a small increase in transcriptional activity, but not restoration to wildtype levels. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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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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Bitner-Glindzicz, M., Turnpenny, P., Hoglund, P., Kaariainen, H., Sankila, E.-M., van der Maarel, S. M., de Kok, Y. J. M., Ropers, H.-H., Cremers, F. P. M., Pembrey, M., Malcolm, S.
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<strong>Further mutations in brain 4 (POU3F4) clarify the phenotype in the X-linked deafness, DFN3.</strong>
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Hum. Molec. Genet. 4: 1467-1469, 1995.
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[PubMed: 7581392]
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[Full Text: https://doi.org/10.1093/hmg/4.8.1467]
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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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Choi, B. Y., Kim, D.-H., Chung, T., Chang, M., Kim, E.-H., Kim, A. R., Seok, J., Chang, S. O., Bok, J., Kim, D., Oh, S.-H., Park, W.-Y.
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<strong>Destabilization and mislocalization of POU3F4 by C-terminal frameshift truncation and extension mutation.</strong>
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Hum. Mutat. 34: 309-316, 2013.
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[PubMed: 23076972]
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[Full Text: https://doi.org/10.1002/humu.22232]
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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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Crovetto, M. A., Whyte, J., Sarasola, E., Rodriguez, J. A., Garcia-Barcina, M. J.
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<strong>Absence of COCH gene mutations in patients with superior semicircular canal dehiscence. (Letter)</strong>
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Am. J. Med. Genet. 158A: 251-253, 2012.
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[PubMed: 22139968]
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[Full Text: https://doi.org/10.1002/ajmg.a.34377]
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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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de Kok, Y. J. M., Cremers, C. W. R. J., Ropers, H.-H., Cremers, F. P. M.
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<strong>The molecular basis of X-linked deafness type 3 (DFN3) in two sporadic cases: identification of a somatic mosaicism for a POU3F4 missense mutation.</strong>
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Hum. Mutat. 10: 207-211, 1997.
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[PubMed: 9298820]
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[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1997)10:3<207::AID-HUMU5>3.0.CO;2-F]
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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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de Kok, Y. J. M., Merkx, G. F. M., van der Maarel, S. M., Huber, I., Malcolm, S., Ropers, H.-H., Cremers, F. P. M.
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<strong>A duplication/paracentric inversion associated with familial X-linked deafness (DFN3) suggests the presence of a regulatory element more than 400 kb upstream of the POU3F4 gene.</strong>
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Hum. Molec. Genet. 4: 2145-2150, 1995.
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[PubMed: 8589693]
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[Full Text: https://doi.org/10.1093/hmg/4.11.2145]
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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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de Kok, Y. J. M., van der Maarel, S. M., Bitner-Glindzicz, M., Huber, I., Monaco, A. P., Malcolm, S., Pembrey, M. E., Ropers, H.-H., Cremers, F. P. M.
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<strong>Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4.</strong>
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Science 267: 685-688, 1995.
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[PubMed: 7839145]
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[Full Text: https://doi.org/10.1126/science.7839145]
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</li>
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<li>
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<p class="mim-text-font">
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Douville, P. J., Atanasoski, S., Tobler, A., Fontana, A., Schwab, M. E.
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<strong>The brain-specific POU-box gene Brn4 is a sex-linked transcription factor located on the human and mouse X chromosomes.</strong>
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Mammalian Genome 5: 180-182, 1994.
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[PubMed: 7911044]
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[Full Text: https://doi.org/10.1007/BF00352353]
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<li>
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<p class="mim-text-font">
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Friedman, R. A., Bykhovskaya, Y., Tu, G., Talbot, J. M., Wilson, D. F., Parnes, L. S., Fischel-Ghodsian, N.
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<strong>Molecular analysis of the POU3F4 gene in patients with clinical and radiographic evidence of X-linked mixed deafness with perilymphatic gusher.</strong>
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Ann. Otol. Rhinol. Laryng. 106: 320-325, 1997.
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[PubMed: 9109724]
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[Full Text: https://doi.org/10.1177/000348949710600411]
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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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Minowa, O., Ikeda, K., Sugitani, Y., Oshima, T., Nakai, S., Katori, Y., Suzuki, M., Furukawa, M., Kawase, T., Zheng, Y., Ogura, M., Asada, Y., Watanabe, K., Yamanaka, H., Gotoh, S., Nishi-Takeshima, M., Sugimoto, T., Kikuchi, T., Takasaka, T., Noda, T.
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<strong>Altered cochlear fibrocytes in a mouse model of DFN3 nonsyndromic deafness.</strong>
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Science 285: 1408-1411, 1999.
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[PubMed: 10464101]
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[Full Text: https://doi.org/10.1126/science.285.5432.1408]
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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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Phelps, P. D., Reardon, W., Pembrey, M., Bellman, S., Luxom, L.
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<strong>X-linked deafness, stapes gushers and a distinctive defect of the inner ear.</strong>
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Neuroradiology 33: 326-330, 1991.
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[PubMed: 1922747]
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[Full Text: https://doi.org/10.1007/BF00587816]
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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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Phippard, D., Boyd, Y., Reed, V., Fisher, G., Masson, W. K., Evans, E. P., Saunders, J. C., Crenshaw, E. B., III.
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<strong>The sex-linked fidget mutation abolishes Brn4/Pou3f4 gene expression in the embryonic inner ear.</strong>
|
|
Hum. Molec. Genet. 9: 79-85, 2000.
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[PubMed: 10587581]
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[Full Text: https://doi.org/10.1093/hmg/9.1.79]
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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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Reardon, W., Middleton-Price, H. R., Sandkuijl, L., Phelps, P., Bellman, S., Luxon, L., Pembrey, M. E., Malcolm, S.
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<strong>A multipedigree linkage study of X-linked deafness: linkage to Xq13-q21 and evidence for genetic heterogeneity.</strong>
|
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Genomics 11: 885-894, 1991.
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[PubMed: 1783396]
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[Full Text: https://doi.org/10.1016/0888-7543(91)90011-3]
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</p>
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</li>
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</ol>
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<div>
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<br />
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<div 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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Cassandra L. Kniffin - updated : 3/27/2013<br>Cassandra L. Kniffin - updated : 2/16/2012<br>Ada Hamosh - updated : 4/18/2001<br>Ada Hamosh - updated : 2/1/2000<br>Victor A. McKusick - updated : 10/10/1997<br>Victor A. McKusick - updated : 6/21/1997<br>Victor A. McKusick - updated : 3/6/1997
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Victor A. McKusick : 3/12/1996
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alopez : 03/20/2023<br>carol : 06/23/2016<br>carol : 3/3/2015<br>carol : 9/12/2013<br>carol : 4/1/2013<br>ckniffin : 3/27/2013<br>carol : 5/17/2012<br>ckniffin : 5/16/2012<br>carol : 2/16/2012<br>ckniffin : 2/16/2012<br>carol : 5/24/2011<br>carol : 4/16/2009<br>wwang : 3/18/2008<br>ckniffin : 8/28/2002<br>carol : 11/24/2001<br>alopez : 4/19/2001<br>terry : 4/18/2001<br>alopez : 2/2/2000<br>terry : 2/1/2000<br>jenny : 10/17/1997<br>terry : 10/10/1997<br>alopez : 7/10/1997<br>terry : 6/24/1997<br>terry : 6/21/1997<br>jenny : 3/6/1997<br>terry : 2/13/1997<br>joanna : 3/14/1996<br>mark : 3/14/1996
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