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Entry
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- *602225 - CONE-ROD HOMEOBOX-CONTAINING GENE; CRX
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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>
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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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<div class="row">
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<p />
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</div>
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<!-- <div id="mimSearch"> -->
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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>
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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">*602225</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="#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="#geneFunction">Gene Function</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/602225">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=ENSG00000105392;t=ENST00000221996" 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=1406" 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=602225" 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=ENSG00000105392;t=ENST00000221996" 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_000554" 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_000554" 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=602225" 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
|
|
</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=03748&isoform_id=03748_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/CRX" 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/2665534,3287764,4557489,16741738,30583567,31565779,85067812,90110488,119577919,129562628" 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/O43186" 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=1406" 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=ENSG00000105392;t=ENST00000221996" 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=CRX" 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=CRX" 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+1406" 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/CRX" 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:1406" 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/1406" 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=chr19&hgg_gene=ENST00000221996.12&hgg_start=47821937&hgg_end=47843324&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:2383" 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/crx" 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=602225[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=602225[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/CRX/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/ENSG00000105392" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=CRX" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=CRX" 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=CRX" 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="http://www.retina-international.org/files/sci-news/crxmut.htm" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=CRX&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/PA26903" 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:2383" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1194883" 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/CRX#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:1194883" 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/1406/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA000881/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=1406" 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=WBGene00000458;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-010403-1" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=CRX&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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602225
|
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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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|
CONE-ROD HOMEOBOX-CONTAINING GENE; CRX
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</span>
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</h3>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=CRX" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CRX</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/19/881?start=-3&limit=10&highlight=881">19q13.33</a>
|
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr19:47821937-47843324&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'})">19:47,821,937-47,843,324</a> </span>
|
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</em>
|
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</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>
|
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<br />
|
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</div>
|
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
|
<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">
|
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<thead>
|
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<tr class="active">
|
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<th>
|
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Location
|
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</th>
|
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<th>
|
|
Phenotype
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<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=120970,613829" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
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|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
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<th>
|
|
Inheritance
|
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</th>
|
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<th>
|
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Phenotype <br /> mapping key
|
|
</th>
|
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</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/19/881?start=-3&limit=10&highlight=881">
|
|
19q13.33
|
|
</a>
|
|
</span>
|
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</td>
|
|
|
|
|
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<td>
|
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<span class="mim-font">
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<p>To identify retinal homeobox-containing genes, <a href="#4" class="mim-tip-reference" title="Freund, C. L., Gregory-Evans, C. Y., Furukawa, T., Papaioannou, M., Looser, J., Ploder, L., Bellingham, J., Ng, D., Herbrick, J. A., Duncan, A., Scherer, S. W., Tsui, L. C., Loutradis-Anagnostou, A., Jacobson, S. G., Cepko, C. L., Bhattacharya, S. S., McInnes, R. R. <strong>Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor.</strong> Cell 91: 543-553, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9390563/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9390563</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80440-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9390563">Freund et al. (1997)</a> screened a human retina cDNA library at low stringency with a fragment from the human CHX10 (<a href="/entry/142993">142993</a>) cDNA. One of the isolated cDNAs encoded a novel gene, which the authors termed CRX for 'cone-rod homeobox-containing gene.' CRX encodes a 299-amino acid protein with a predicted mass of 32 kD that is most similar to the human OTX1 (<a href="/entry/600036">600036</a>) and OTX2 (<a href="/entry/600037">600037</a>) homeodomain proteins. The CRX homeodomain is located near the amino terminus at residues 39 to 99 and belongs to the prd class. Additional domains of the CRX protein include the WSP motif and the OTX tail. The CRX gene was expressed as an abundant 4.5-kb transcript in retina but not in any other of 10 tissues or cells examined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9390563" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Furukawa, T., Morrow, E. M., Cepko, C. L. <strong>Crx, a novel otx-like homeobox gene, shows photoreceptor-specific expression and regulates photoreceptor differentiation.</strong> Cell 91: 531-541, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9390562/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9390562</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80439-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9390562">Furukawa et al. (1997)</a> isolated the mouse Crx gene from mouse retina. The human CRX cDNA is 97% identical to the mouse gene. Crx expression was restricted to developing and mature photoreceptor cells. Crx bound and transactivated the sequence TAATCC/A, which is found upstream of several photoreceptor-specific genes, including the opsin genes from many species. Overexpression of Crx using a retroviral vector increased the frequency of clones containing exclusively rod photoreceptors and reduced the frequency of clones containing amacrine interneurons and Muller glial cells. In addition, presumptive photoreceptor cells expressing a dominant negative form of Crx failed to form proper photoreceptor outer segments and terminals. The authors concluded that Crx is a photoreceptor-specific transcription factor and plays a crucial role in the differentiation of photoreceptor cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9390562" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#1" class="mim-tip-reference" title="Akagi, T., Mandai, M., Ooto, S., Hirami, Y., Osakada, F., Kageyama, R., Yoshimura, N., Takahashi, M. <strong>Otx2 homeobox gene induces photoreceptor-specific phenotypes in cells derived from adult iris and ciliary tissue.</strong> Invest. Ophthal. Vis. Sci. 45: 4570-4575, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15557469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15557469</a>] [<a href="https://doi.org/10.1167/iovs.04-0697" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15557469">Akagi et al. (2004)</a> reported that CRX and OTX2 effectively induced the generation of photoreceptor-specific phenotypes from ciliary- and iris-derived cells of adult rat. More than 90% of the CRX- and OTX2-transfected ciliary- and iris-derived cells exhibited rod opsin immunoreactivity, whereas few of the similarly transfected mesencephalon-derived neural stem cells from embryonic rat expressed rod opsin. At least 2 additional key components of the phototransduction cascade, recoverin (<a href="/entry/179618">179618</a>) and G-delta-T1, were expressed by CRX- and OTX2-transfected iris-derived cells. <a href="#1" class="mim-tip-reference" title="Akagi, T., Mandai, M., Ooto, S., Hirami, Y., Osakada, F., Kageyama, R., Yoshimura, N., Takahashi, M. <strong>Otx2 homeobox gene induces photoreceptor-specific phenotypes in cells derived from adult iris and ciliary tissue.</strong> Invest. Ophthal. Vis. Sci. 45: 4570-4575, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15557469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15557469</a>] [<a href="https://doi.org/10.1167/iovs.04-0697" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15557469">Akagi et al. (2004)</a> concluded that CRX and OTX2 induced phenotype generation in cells derived from iris or ciliary tissue, which may suggest an approach to photoreceptor cell preparation for retinal transplantation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15557469" 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>Spinocerebellar ataxia type 7 (SCA7; <a href="/entry/164500">164500</a>) is an inherited neurodegenerative disorder caused by expansion of a polyglutamine tract in the ataxin-7 (ATXN7; <a href="/entry/607640">607640</a>) protein. A unique feature of SCA7 is degeneration of photoreceptor cells in the retina, resulting in cone-rod dystrophy. In an SCA7 transgenic mouse model, <a href="#10" class="mim-tip-reference" title="La Spada, A. R., Fu, Y.-H., Sopher, B. L., Libby, R. T., Wang, X., Li, L. Y., Einum, D. D., Huang, J., Possin, D. E., Smith, A. C., Martinez, R. A., Koszdin, K. L., Treuting, P. M., Ware, C. B., Hurley, J. B., Ptacek, L. J., Chen, S. <strong>Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7.</strong> Neuron 31: 913-927, 2001. Note: Erratum: Neuron 32: 957-958, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11580893/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11580893</a>] [<a href="https://doi.org/10.1016/s0896-6273(01)00422-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11580893">La Spada et al. (2001)</a> found that the cone-rod dystrophy involved altered photoreceptor gene expression due to interference with CRX. By coimmunoprecipitation analysis of CRX and ATXN7 truncation and point mutants, <a href="#2" class="mim-tip-reference" title="Chen, S., Peng, G.-H., Wang, X., Smith, A. C., Grote, S. K., Sopher, B. L., La Spada, A. R. <strong>Interference of Crx-dependent transcription by ataxin-7 involves interaction between the glutamine regions and requires the ataxin-7 carboxy-terminal region for nuclear localization.</strong> Hum. Molec. Genet. 13: 53-67, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14613968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14613968</a>] [<a href="https://doi.org/10.1093/hmg/ddh005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14613968">Chen et al. (2004)</a> determined that the ATXN7-interacting domain of CRX localized to its glutamine-rich region and that the CRX-interacting domain of ATXN7 localized to its glutamine tract. Nuclear localization of ataxin-7 was required to repress Crx transactivation, and the likely nuclear localization signals were mapped to the C-terminal region of ataxin-7. Using chromatin immunoprecipitation, the authors showed that both Crx and ataxin-7 occupied the promoter and enhancer regions of Crx-regulated retinal genes in vivo. <a href="#2" class="mim-tip-reference" title="Chen, S., Peng, G.-H., Wang, X., Smith, A. C., Grote, S. K., Sopher, B. L., La Spada, A. R. <strong>Interference of Crx-dependent transcription by ataxin-7 involves interaction between the glutamine regions and requires the ataxin-7 carboxy-terminal region for nuclear localization.</strong> Hum. Molec. Genet. 13: 53-67, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14613968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14613968</a>] [<a href="https://doi.org/10.1093/hmg/ddh005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14613968">Chen et al. (2004)</a> suggested that one mechanism of SCA7 disease pathogenesis may be transcription dysregulation, and that CRX transcription interference may be a predominant factor in SCA7 cone-rod dystrophy retinal degeneration. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14613968+11580893" 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>Using a combination of in situ hybridization, somatic cell hybrid and radiation hybrid mapping, and yeast artificial chromosome contig analysis, <a href="#4" class="mim-tip-reference" title="Freund, C. L., Gregory-Evans, C. Y., Furukawa, T., Papaioannou, M., Looser, J., Ploder, L., Bellingham, J., Ng, D., Herbrick, J. A., Duncan, A., Scherer, S. W., Tsui, L. C., Loutradis-Anagnostou, A., Jacobson, S. G., Cepko, C. L., Bhattacharya, S. S., McInnes, R. R. <strong>Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor.</strong> Cell 91: 543-553, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9390563/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9390563</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80440-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9390563">Freund et al. (1997)</a> mapped the CRX gene to 19q13.3 in the interval between markers D19S219 and D19S246 in the critical region of the cone-rod dystrophy-2 locus (CORD2; <a href="/entry/120970">120970</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9390563" 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="#4" class="mim-tip-reference" title="Freund, C. L., Gregory-Evans, C. Y., Furukawa, T., Papaioannou, M., Looser, J., Ploder, L., Bellingham, J., Ng, D., Herbrick, J. A., Duncan, A., Scherer, S. W., Tsui, L. C., Loutradis-Anagnostou, A., Jacobson, S. G., Cepko, C. L., Bhattacharya, S. S., McInnes, R. R. <strong>Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor.</strong> Cell 91: 543-553, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9390563/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9390563</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80440-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9390563">Freund et al. (1997)</a> found a missense and a frameshift mutation in the CRX gene in 2 pedigrees with CORD2 (<a href="/entry/120970">120970</a>). The authors showed that the missense (<a href="#0001">602225.0001</a>) mutation was not a polymorphic variant and concluded that mutation in the CRX gene is responsible for the CORD2 phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9390563" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Swain, P. K., Chen, S., Wang, Q.-L., Affatigato, L. M., Coats, C. L., Brady, K. D., Fishman, G. A., Jacobson, S. G., Swaroop, A., Stone, E., Sieving, P. A., Zack, D. J. <strong>Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration.</strong> Neuron 19: 1329-1336, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9427255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9427255</a>] [<a href="https://doi.org/10.1016/s0896-6273(00)80423-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9427255">Swain et al. (1997)</a> found an arg41-to-trp substitution in the third residue of the CRX homeodomain in the proband from a family with autosomal dominant CORD. The sequence change cosegregated with the disease phenotype and was not detected in 247 normal controls. The data suggested that mutations in the CRX gene are associated with photoreceptor degeneration and that the Crx protein is necessary for the maintenance of normal cone and rod function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9427255" 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>Because CRX is essential for photoreceptor maintenance and because expression of a dominant-negative CRX allele in developing retina prevented outer segment biogenesis (<a href="#6" class="mim-tip-reference" title="Furukawa, T., Morrow, E. M., Cepko, C. L. <strong>Crx, a novel otx-like homeobox gene, shows photoreceptor-specific expression and regulates photoreceptor differentiation.</strong> Cell 91: 531-541, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9390562/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9390562</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80439-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9390562">Furukawa et al., 1997</a>), <a href="#5" class="mim-tip-reference" title="Freund, C. L., Wang, Q.-L., Chen, S., Muskat, B. L., Wiles, C. D., Sheffield, V. C., Jacobson, S. G., McInnes, R. R., Zack, D. J., Stone, E. M. <strong>De novo mutations in the CRX homeobox gene associated with Leber congenital amaurosis. (Letter)</strong> Nature Genet. 18: 311-312, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537410</a>] [<a href="https://doi.org/10.1038/ng0498-311" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537410">Freund et al. (1998)</a> tested the hypothesis that CRX mutations are responsible for some cases of the Leber congenital amaurosis phenotype by examining the CRX gene of 74 Leber congenital amaurosis patients. They identified 2 patients with a de novo deletion mutation (<a href="#0003">602225.0003</a>-<a href="#0004">602225.0004</a>, respectively) as the cause of Leber congenital amaurosis-7 (LCA7; <a href="/entry/613829">613829</a>). Their findings indicated that the product of the CRX gene is essential not only for normal maintenance of the photoreceptor, as demonstrated by mutations causing autosomal dominant cone-rod dystrophy (<a href="/entry/120970">120970</a>), but also possibly essential for early photoreceptor development. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9390562+9537410" 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>CRX is a transcription factor for several retinal genes, including the opsins and the gene for interphotoreceptor retinoid-binding protein. Because loss of CRX function could alter the expression of a number of other retinal proteins, <a href="#16" class="mim-tip-reference" title="Sohocki, M. M., Sullivan, L. S., Mintz-Hittner, H. A., Birch, D., Heckenlively, J. R., Freund, C. L., McInnes, R. R., Daiger, S. P. <strong>A range of clinical phenotypes associated with mutations in CRX, a photoreceptor transcription-factor gene.</strong> Am. J. Hum. Genet. 63: 1307-1315, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9792858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9792858</a>] [<a href="https://doi.org/10.1086/302101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9792858">Sohocki et al. (1998)</a> screened for mutations in the CRX gene in probands with a range of degenerative retinal diseases. Of the 294 unrelated individuals screened, they identified 4 CRX mutations in families with clinical diagnoses of autosomal dominant cone-rod dystrophy, late-onset dominant retinitis pigmentosa, or dominant Leber congenital amaurosis (early-onset retinitis pigmentosa), and they identified 4 additional benign sequence variants. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9792858" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Rivolta, C., Berson, E. L., Dryja, T. P. <strong>Dominant Leber congenital amaurosis, cone-rod degeneration, and retinitis pigmentosa caused by mutant versions of the transcription factor CRX.</strong> Hum. Mutat. 18: 488-498, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11748842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11748842</a>] [<a href="https://doi.org/10.1002/humu.1226" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11748842">Rivolta et al. (2001)</a> summarized 18 mutations in the CRX gene associated with retinal abnormalities. Except for 1 obviously null allele not definitely associated with a phenotype (a frameshift in codon 9), all CRX mutations appeared to be completely penetrant and caused disease in heterozygotes. These dominant alleles fell into 2 categories. In one group were missense mutations and short, in-frame deletions; in the second group were frameshift mutations, all of which were in the last exon. All of these dominant mutations were likely to produce stable mRNA that is translated. <a href="#15" class="mim-tip-reference" title="Rivolta, C., Berson, E. L., Dryja, T. P. <strong>Dominant Leber congenital amaurosis, cone-rod degeneration, and retinitis pigmentosa caused by mutant versions of the transcription factor CRX.</strong> Hum. Mutat. 18: 488-498, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11748842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11748842</a>] [<a href="https://doi.org/10.1002/humu.1226" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11748842">Rivolta et al. (2001)</a> did not detect a correlation between type of disease and type of mutation. Four of the mutations were de novo and these were found in isolated cases of Leber congenital amaurosis. <a href="#15" class="mim-tip-reference" title="Rivolta, C., Berson, E. L., Dryja, T. P. <strong>Dominant Leber congenital amaurosis, cone-rod degeneration, and retinitis pigmentosa caused by mutant versions of the transcription factor CRX.</strong> Hum. Mutat. 18: 488-498, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11748842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11748842</a>] [<a href="https://doi.org/10.1002/humu.1226" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11748842">Rivolta et al. (2001)</a> noted that dominant CRX mutations have not been associated with mental retardation or developmental delay that has sometimes been found in Leber congenital amaurosis caused by mutation in other genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11748842" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Chen, S., Wang, Q.-L., Xu, S., Liu, I., Li, L. Y., Wang, Y., Zack, D. J. <strong>Functional analysis of cone-rod homeobox (CRX) mutations associated with retinal dystrophy.</strong> Hum. Molec. Genet. 11: 873-884, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11971869/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11971869</a>] [<a href="https://doi.org/10.1093/hmg/11.8.873" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11971869">Chen et al. (2002)</a> used transient transfection and mobility shift assays to investigate the consequences of 11 known mutations in CRX in vitro. They demonstrated that the C-terminal region, between amino acids 200 and 284, is essential for CRX-mediated transcriptional activation. Three homeodomain missense mutations (R41W, <a href="#0005">602225.0005</a>; R41Q, <a href="#0006">602225.0006</a>; and R90W, <a href="#0007">602225.0007</a>) displayed decreased transactivating activity, and E80A (<a href="#0001">602225.0001</a>) demonstrated markedly increased activity. In vitro protein-DNA binding assays with mutant CRX homeodomain peptides demonstrated that the alteration was due to reduced DNA binding to CRX targets. The authors hypothesized that CRX mutations involved in human photoreceptor degeneration act by impairing CRX-mediated transcriptional regulation of the photoreceptor genes. However, since a clear relationship between the magnitude of biochemical abnormality and degree of disease severity was not observed, the authors suggested that other genetic and environmental modifiers may also contribute to the disease phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11971869" 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>CRX is expressed not only in the photoreceptors of the retina, but also in the pinealocytes of the pineal gland. <a href="#7" class="mim-tip-reference" title="Furukawa, T., Morrow, E. M., Li, T., Davis, F. C., Cepko, C. L. <strong>Retinopathy and attenuated circadian entrainment in Crx-deficient mice.</strong> Nature Genet. 23: 466-470, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10581037/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10581037</a>] [<a href="https://doi.org/10.1038/70591" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10581037">Furukawa et al. (1999)</a> generated mice carrying a targeted disruption of Crx. Homozygous deficient mice did not elaborate photoreceptor outer segments and lacked rod and cone activity as assayed by electroretinogram. Expression of several photoreceptor- and pineal-specific genes was reduced in Crx mutants. Circadian entrainment was also affected in Crx -/- mice. To examine photoentrainment activity in homozygous deficient mice, <a href="#7" class="mim-tip-reference" title="Furukawa, T., Morrow, E. M., Li, T., Davis, F. C., Cepko, C. L. <strong>Retinopathy and attenuated circadian entrainment in Crx-deficient mice.</strong> Nature Genet. 23: 466-470, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10581037/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10581037</a>] [<a href="https://doi.org/10.1038/70591" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10581037">Furukawa et al. (1999)</a> recorded the activity of wildtype and Crx -/- mice running on an exercise wheel. All mice showed robust 24-hour rhythms in activity during entrainment and in constant darkness. All mice showed the most activity during the dark interval of a 24-hour period. The percentage of total activity that occurred at night, however, was significantly less in homozygous deficient mice than in wildtype mice. All mice re-entrained to the light-dark cycle following an advance of 4 hours in the cycle; however, the number of days required to complete the shift was greater in Crx -/- mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10581037" 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>Zebrafish proved a useful model for studying circadian gene regulation and pineal organ function. The Crx gene was thought to regulate pineal circadian activity. In the mouse, targeted inactivation of Crx caused a reduction in pineal gene expression and attenuated entrainment to light/dark cycles (<a href="#7" class="mim-tip-reference" title="Furukawa, T., Morrow, E. M., Li, T., Davis, F. C., Cepko, C. L. <strong>Retinopathy and attenuated circadian entrainment in Crx-deficient mice.</strong> Nature Genet. 23: 466-470, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10581037/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10581037</a>] [<a href="https://doi.org/10.1038/70591" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10581037">Furukawa et al., 1999</a>). <a href="#8" class="mim-tip-reference" title="Gamse, J. T., Shen, Y.-C., Thisse, C., Thisse, B., Raymond, P. A., Halpern, M. E., Liang, J. O. <strong>Otx5 regulates genes that show circadian expression in the zebrafish pineal complex.</strong> Nature Genet. 30: 117-121, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11753388/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11753388</a>] [<a href="https://doi.org/10.1038/ng793" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11753388">Gamse et al. (2002)</a> showed that Crx and Otx5 (orthodenticle homeobox-5) orthologs are expressed in both the pineal organ and the asymmetrically positioned parapineal of larval zebrafish. Circadian gene expression was unaffected by a reduction in Crx expression but was inhibited specifically by depletion of Otx5. These results indicate that Otx5 rather than Crx regulates genes that show circadian expression in the zebrafish pineal complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11753388+10581037" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using expression studies in transgenic mice under conditional Otx2 (<a href="/entry/600037">600037</a>) gene ablation, <a href="#13" class="mim-tip-reference" title="Nishida, A., Furukawa, A., Koike, C., Tano, Y., Aizawa, S., Matsuo, I., Furukawa, T. <strong>Otx2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development.</strong> Nature Neurosci. 6: 1255-1263, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14625556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14625556</a>] [<a href="https://doi.org/10.1038/nn1155" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14625556">Nishida et al. (2003)</a> presented evidence that Otx2 is a direct upstream regulator of Crx and acts via binding to specific consensus sequences in the Crx promoter. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14625556" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Menotti-Raymond, M., Deckman, K. H., David, V., Myrkalo, J., O'Brien, S. J., Narfstrom, K. <strong>Mutation discovered in a feline model of human congenital retinal blinding disease.</strong> Invest. Ophthal. Vis. Sci. 51: 2852-2859, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20053974/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20053974</a>] [<a href="https://doi.org/10.1167/iovs.09-4261" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20053974">Menotti-Raymond et al. (2010)</a> identified a putative mutation in the CRX gene (546delC) as the cause of autosomal dominant rod-cone dysplasia (Rdy) in a pedigree of cats segregating for the disorder. Disease expression in Rdy cats is comparable to that in young patients with Leber congenital amaurosis or retinitis pigmentosa. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20053974" 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 Greek family with autosomal dominant CORD2 (<a href="/entry/120970">120970</a>), <a href="#4" class="mim-tip-reference" title="Freund, C. L., Gregory-Evans, C. Y., Furukawa, T., Papaioannou, M., Looser, J., Ploder, L., Bellingham, J., Ng, D., Herbrick, J. A., Duncan, A., Scherer, S. W., Tsui, L. C., Loutradis-Anagnostou, A., Jacobson, S. G., Cepko, C. L., Bhattacharya, S. S., McInnes, R. R. <strong>Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor.</strong> Cell 91: 543-553, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9390563/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9390563</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80440-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9390563">Freund et al. (1997)</a> identified a GAG-to-GCG mutation at codon 80 of one allele of the CRX gene. The mutation was not a common polymorphism in the Greek population since it was not found in more than 100 normal Greek alleles or in more than 600 other Caucasian control alleles examined. The glu80-to-ala mutation is located within the CRX homeodomain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9390563" 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">rs1568626209 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1568626209;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=rs1568626209" 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=rs1568626209" 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=RCV000007842" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007842" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007842</a>
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<p>In a northern European family with autosomal dominant CORD2 (<a href="/entry/120970">120970</a>), <a href="#4" class="mim-tip-reference" title="Freund, C. L., Gregory-Evans, C. Y., Furukawa, T., Papaioannou, M., Looser, J., Ploder, L., Bellingham, J., Ng, D., Herbrick, J. A., Duncan, A., Scherer, S. W., Tsui, L. C., Loutradis-Anagnostou, A., Jacobson, S. G., Cepko, C. L., Bhattacharya, S. S., McInnes, R. R. <strong>Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor.</strong> Cell 91: 543-553, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9390563/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9390563</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80440-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9390563">Freund et al. (1997)</a> identified a deletion of G at nucleotide 502 of one allele of the CRX cDNA (codon 168). This deletion results in a frameshift and premature termination of the CRX protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9390563" 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">rs61748446 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61748446;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=rs61748446" 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=rs61748446" 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=RCV000086005 OR RCV002274927" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000086005, RCV002274927" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000086005...</a>
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<p>Using SSCP analysis and direct sequencing of PCR-amplified exons of the CRX gene, <a href="#5" class="mim-tip-reference" title="Freund, C. L., Wang, Q.-L., Chen, S., Muskat, B. L., Wiles, C. D., Sheffield, V. C., Jacobson, S. G., McInnes, R. R., Zack, D. J., Stone, E. M. <strong>De novo mutations in the CRX homeobox gene associated with Leber congenital amaurosis. (Letter)</strong> Nature Genet. 18: 311-312, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537410</a>] [<a href="https://doi.org/10.1038/ng0498-311" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537410">Freund et al. (1998)</a> identified putative disease-causing de novo deletion mutations in CRX in 2 patients with Leber congenital amaurosis-7 (<a href="/entry/613829">613829</a>): a 2-bp deletion at the glu168 codon (E168del2bp) and a 1-bp deletion at the gly217 codon (G217del1bp; <a href="#0004">602225.0004</a>). Both deletions caused frameshifts, and the predicted proteins lacked the conserved carboxy-terminal tail. The E168del2bp allele had lost an AG dinucleotide from the GAG codon for the eleventh residue within the conserved 13-amino acid WSP motif. If the mRNA containing this premature stop codon were stable, 45% of the protein would be lost and replaced with a new C terminus of 4 amino acids (VPFA). The G217del1bp allele was due to deletion of a G nucleotide, also within a short conserved sequence, and the predicted protein would lack 25% of the C terminus, with 1 new amino acid (alanine) encoded after the frameshift. Curiously, the E168del2bp mutation occurred within the same codon as a mutation found in an autosomal dominant cone-rod dystrophy family (<a href="#0003">602225.0003</a>). Both E168 and G217 are followed by polypyrimidine runs, a feature commonly associated with deletions. Neither mutation was present in any of the parents or in 360 control CRX alleles. <a href="#5" class="mim-tip-reference" title="Freund, C. L., Wang, Q.-L., Chen, S., Muskat, B. L., Wiles, C. D., Sheffield, V. C., Jacobson, S. G., McInnes, R. R., Zack, D. J., Stone, E. M. <strong>De novo mutations in the CRX homeobox gene associated with Leber congenital amaurosis. (Letter)</strong> Nature Genet. 18: 311-312, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537410</a>] [<a href="https://doi.org/10.1038/ng0498-311" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537410">Freund et al. (1998)</a> stated that although they were unable to identify a mutation in the other CRX allele of either patient, both might nevertheless carry a second CRX mutation (such as a promoter or mid-intron mutation) that remains to be discovered. If that is the case, the inheritance would be recessive. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9537410" 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">rs281865517 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865517;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=rs281865517" 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=rs281865517" 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=RCV000086016 OR RCV002274928" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000086016, RCV002274928" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000086016...</a>
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<p>See <a href="#0003">602225.0003</a> and <a href="#5" class="mim-tip-reference" title="Freund, C. L., Wang, Q.-L., Chen, S., Muskat, B. L., Wiles, C. D., Sheffield, V. C., Jacobson, S. G., McInnes, R. R., Zack, D. J., Stone, E. M. <strong>De novo mutations in the CRX homeobox gene associated with Leber congenital amaurosis. (Letter)</strong> Nature Genet. 18: 311-312, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537410</a>] [<a href="https://doi.org/10.1038/ng0498-311" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537410">Freund et al. (1998)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9537410" 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 CONE-ROD DYSTROPHY 2</strong>
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CRX, ARG41TRP
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894672 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894672;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104894672?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894672" 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=rs104894672" 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=RCV000007843 OR RCV000085989 OR RCV001073396 OR RCV001386169 OR RCV003324484 OR RCV003324485" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007843, RCV000085989, RCV001073396, RCV001386169, RCV003324484, RCV003324485" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007843...</a>
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<p>In the proband from a family with autosomal dominant CORD2 (<a href="/entry/120970">120970</a>), <a href="#17" class="mim-tip-reference" title="Swain, P. K., Chen, S., Wang, Q.-L., Affatigato, L. M., Coats, C. L., Brady, K. D., Fishman, G. A., Jacobson, S. G., Swaroop, A., Stone, E., Sieving, P. A., Zack, D. J. <strong>Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration.</strong> Neuron 19: 1329-1336, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9427255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9427255</a>] [<a href="https://doi.org/10.1016/s0896-6273(00)80423-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9427255">Swain et al. (1997)</a> found an arg41-to-trp substitution in the third residue of the CRX homeodomain. The substitution caused a decrease in DNA binding activity. The sequence change cosegregated with the disease phenotype and was not detected in 247 normal controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9427255" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs61748436 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61748436;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs61748436?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs61748436" 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=rs61748436" 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=RCV000007846 OR RCV000085990 OR RCV001059718 OR RCV001075469 OR RCV001263020 OR RCV004755718" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007846, RCV000085990, RCV001059718, RCV001075469, RCV001263020, RCV004755718" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007846...</a>
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<p>In the proband from a family segregating autosomal dominant cone-rod dystrophy-2 (<a href="/entry/120970">120970</a>), <a href="#17" class="mim-tip-reference" title="Swain, P. K., Chen, S., Wang, Q.-L., Affatigato, L. M., Coats, C. L., Brady, K. D., Fishman, G. A., Jacobson, S. G., Swaroop, A., Stone, E., Sieving, P. A., Zack, D. J. <strong>Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration.</strong> Neuron 19: 1329-1336, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9427255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9427255</a>] [<a href="https://doi.org/10.1016/s0896-6273(00)80423-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9427255">Swain et al. (1997)</a> identified a G-to-A transition in the CRX gene, resulting in an arg41-to-gln (R41Q) substitution. This mutation involves the same codon as the arg41-to-trp mutation (<a href="#0005">602225.0005</a>) found by <a href="#17" class="mim-tip-reference" title="Swain, P. K., Chen, S., Wang, Q.-L., Affatigato, L. M., Coats, C. L., Brady, K. D., Fishman, G. A., Jacobson, S. G., Swaroop, A., Stone, E., Sieving, P. A., Zack, D. J. <strong>Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration.</strong> Neuron 19: 1329-1336, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9427255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9427255</a>] [<a href="https://doi.org/10.1016/s0896-6273(00)80423-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9427255">Swain et al. (1997)</a> in a patient with autosomal dominant CORD2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9427255" 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="#16" class="mim-tip-reference" title="Sohocki, M. M., Sullivan, L. S., Mintz-Hittner, H. A., Birch, D., Heckenlively, J. R., Freund, C. L., McInnes, R. R., Daiger, S. P. <strong>A range of clinical phenotypes associated with mutations in CRX, a photoreceptor transcription-factor gene.</strong> Am. J. Hum. Genet. 63: 1307-1315, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9792858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9792858</a>] [<a href="https://doi.org/10.1086/302101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9792858">Sohocki et al. (1998)</a> identified the R41Q mutation in a proband originally diagnosed with late-onset dominant retinitis pigmentosa. The authors stated that later analysis of additional members of this family suggested an alternative diagnosis of late-onset, atypical, cone-rod dystrophy. None of the other 163 probands with a diagnosis of autosomal dominant RP studied by <a href="#16" class="mim-tip-reference" title="Sohocki, M. M., Sullivan, L. S., Mintz-Hittner, H. A., Birch, D., Heckenlively, J. R., Freund, C. L., McInnes, R. R., Daiger, S. P. <strong>A range of clinical phenotypes associated with mutations in CRX, a photoreceptor transcription-factor gene.</strong> Am. J. Hum. Genet. 63: 1307-1315, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9792858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9792858</a>] [<a href="https://doi.org/10.1086/302101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9792858">Sohocki et al. (1998)</a> were found to have a mutation in the CRX gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9792858" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894673 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894673;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104894673?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894673" 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=rs104894673" 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=RCV000007847 OR RCV000086364 OR RCV001074643 OR RCV001244346" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007847, RCV000086364, RCV001074643, RCV001244346" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007847...</a>
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<p>In a patient with Leber congenital amaurosis-7 (<a href="/entry/613829">613829</a>), <a href="#18" class="mim-tip-reference" title="Swaroop, A., Wang, Q.-L., Wu, W., Cook, J., Coats, C., Xu, S., Chen, S., Zack, D. J., Sieving, P. A. <strong>Leber congenital amaurosis caused by a homozygous mutation (R90W) in the homeodomain of the retinal transcription factor CRX: direct evidence for the involvement of CRX in the development of photoreceptor function.</strong> Hum. Molec. Genet. 8: 299-305, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9931337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9931337</a>] [<a href="https://doi.org/10.1093/hmg/8.2.299" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9931337">Swaroop et al. (1999)</a> identified a homozygous substitution of arginine (arg) at codon 90 by tryptophan (trp) in the CRX homeodomain due to a C-to-T transition in exon 3 of the CRX gene. <a href="#18" class="mim-tip-reference" title="Swaroop, A., Wang, Q.-L., Wu, W., Cook, J., Coats, C., Xu, S., Chen, S., Zack, D. J., Sieving, P. A. <strong>Leber congenital amaurosis caused by a homozygous mutation (R90W) in the homeodomain of the retinal transcription factor CRX: direct evidence for the involvement of CRX in the development of photoreceptor function.</strong> Hum. Molec. Genet. 8: 299-305, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9931337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9931337</a>] [<a href="https://doi.org/10.1093/hmg/8.2.299" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9931337">Swaroop et al. (1999)</a> found that the mutant CRX (R90W) homeodomain demonstrated decreased binding to the previously identified cis sequence elements in the rhodopsin promoter. In transient transfection experiments, the mutant protein showed significantly reduced ability to transactivate the rhodopsin promoter, as well as lower synergistic activation with the transcription factor NRL (<a href="/entry/162080">162080</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9931337" 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">rs281865515 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865515;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=rs281865515" 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=rs281865515" 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=RCV000007848 OR RCV000086007" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007848, RCV000086007" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007848...</a>
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<p><a href="#12" class="mim-tip-reference" title="Nakamura, M., Ito, S., Miyake, Y. <strong>Novel de novo mutation in CRX gene in a Japanese patient with Leber congenital amaurosis.</strong> Am. J. Ophthal. 134: 465-467, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12208271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12208271</a>] [<a href="https://doi.org/10.1016/s0002-9394(02)01542-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12208271">Nakamura et al. (2002)</a> reported a novel de novo mutation in the CRX gene in a Japanese patient with Leber congenital amaurosis-7 (<a href="/entry/613829">613829</a>). The CRX gene was analyzed by direct genomic sequencing in the patient with LCA and in his healthy parents. They identified a heterozygous deletion of G at nucleotide 520 in CRX, predicting a frameshift in codon 174 and a premature termination of translation. The mutation was not present in the proband's unaffected parents. Except for CRX, all known genes that cause LCA cause the disorder in an autosomal recessive fashion. This mutation was similar to the other 5 known de novo mutations in CRX because it was a heterozygous deletion of 1 or 2 base pairs in exon 3 causing a frameshift, producing a protein lacking the conserved OTX tail motif near the C terminus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12208271" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs281865516 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865516;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs281865516?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs281865516" 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=rs281865516" 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=RCV000007849 OR RCV000086015 OR RCV001854501 OR RCV003888488" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007849, RCV000086015, RCV001854501, RCV003888488" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007849...</a>
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<p>In a 3-generation Japanese family with cone-rod dystrophy (CORD; <a href="/entry/120970">120970</a>), <a href="#9" class="mim-tip-reference" title="Itabashi, T., Wada, Y., Sato, H., Kawamura, M., Shiono, T., Tamai, M. <strong>Novel 615delC mutation in the CRX gene in a Japanese family with cone-rod dystrophy.</strong> Am. J. Ophthal. 138: 876-877, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15531334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15531334</a>] [<a href="https://doi.org/10.1016/j.ajo.2004.05.067" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15531334">Itabashi et al. (2004)</a> identified a heterozygous deletion of a cytidine at nucleotide 615 in exon 1 of the CRX gene (605delC). Ophthalmic findings included negative-type electroretinogram and rapid progression after age 40 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15531334" 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">rs2123743692 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2123743692;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=rs2123743692" 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=rs2123743692" 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=RCV000007850 OR RCV004814856" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007850, RCV004814856" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007850...</a>
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<p>In a 2-generation German family with cone-rod dystrophy (CORD2; <a href="/entry/120970">120970</a>), <a href="#14" class="mim-tip-reference" title="Paunescu, K., Preising, M. N., Janke, B., Wissinger, B., Lorenz, B. <strong>Genotype-phenotype correlation in a German family with a novel complex CRX mutation extending the open reading frame.</strong> Ophthalmology 114: 1348-1357, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17320181/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17320181</a>] [<a href="https://doi.org/10.1016/j.ophtha.2006.10.034" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17320181">Paunescu et al. (2007)</a> identified a novel heterozygous complex mutation (816delCACinsAA) in the CRX gene, predicting the substitution of 27 C-terminal amino acids by 44 novel amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17320181" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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<a id="Akagi2004" class="mim-anchor"></a>
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[<a href="https://doi.org/10.1167/iovs.04-0697" target="_blank">Full Text</a>]
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<a id="Chen2004" class="mim-anchor"></a>
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Chen, S., Peng, G.-H., Wang, X., Smith, A. C., Grote, S. K., Sopher, B. L., La Spada, A. R.
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<strong>Interference of Crx-dependent transcription by ataxin-7 involves interaction between the glutamine regions and requires the ataxin-7 carboxy-terminal region for nuclear localization.</strong>
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[<a href="https://doi.org/10.1093/hmg/ddh005" target="_blank">Full Text</a>]
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<a id="Chen2002" class="mim-anchor"></a>
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<div class="">
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[<a href="https://doi.org/10.1093/hmg/11.8.873" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0092-8674(00)80440-7" target="_blank">Full Text</a>]
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<a id="Freund1998" class="mim-anchor"></a>
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Freund, C. L., Wang, Q.-L., Chen, S., Muskat, B. L., Wiles, C. D., Sheffield, V. C., Jacobson, S. G., McInnes, R. R., Zack, D. J., Stone, E. M.
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[<a href="https://doi.org/10.1038/ng0498-311" target="_blank">Full Text</a>]
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Furukawa, T., Morrow, E. M., Cepko, C. L.
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[<a href="https://doi.org/10.1016/s0092-8674(00)80439-0" target="_blank">Full Text</a>]
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<a id="Furukawa1999" class="mim-anchor"></a>
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Furukawa, T., Morrow, E. M., Li, T., Davis, F. C., Cepko, C. L.
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[<a href="https://doi.org/10.1038/70591" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11753388/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11753388</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11753388" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng793" target="_blank">Full Text</a>]
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<strong>Novel 615delC mutation in the CRX gene in a Japanese family with cone-rod dystrophy.</strong>
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[<a href="https://doi.org/10.1016/j.ajo.2004.05.067" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0896-6273(01)00422-6" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1167/iovs.09-4261" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12208271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12208271</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12208271" 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/s0002-9394(02)01542-8" target="_blank">Full Text</a>]
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<div class="">
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[<a href="https://doi.org/10.1038/nn1155" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17320181/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17320181</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17320181" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ophtha.2006.10.034" target="_blank">Full Text</a>]
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<a id="Rivolta2001" class="mim-anchor"></a>
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Rivolta, C., Berson, E. L., Dryja, T. P.
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[<a href="https://doi.org/10.1002/humu.1226" target="_blank">Full Text</a>]
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<a id="Sohocki1998" class="mim-anchor"></a>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9792858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9792858</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9792858" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/302101" target="_blank">Full Text</a>]
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<a id="Swain1997" class="mim-anchor"></a>
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Swain, P. K., Chen, S., Wang, Q.-L., Affatigato, L. M., Coats, C. L., Brady, K. D., Fishman, G. A., Jacobson, S. G., Swaroop, A., Stone, E., Sieving, P. A., Zack, D. J.
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<strong>Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration.</strong>
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Neuron 19: 1329-1336, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9427255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9427255</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9427255" 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/s0896-6273(00)80423-7" target="_blank">Full Text</a>]
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<a id="18" class="mim-anchor"></a>
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<a id="Swaroop1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Swaroop, A., Wang, Q.-L., Wu, W., Cook, J., Coats, C., Xu, S., Chen, S., Zack, D. J., Sieving, P. A.
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<strong>Leber congenital amaurosis caused by a homozygous mutation (R90W) in the homeodomain of the retinal transcription factor CRX: direct evidence for the involvement of CRX in the development of photoreceptor function.</strong>
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Hum. Molec. Genet. 8: 299-305, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9931337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9931337</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9931337" 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/8.2.299" target="_blank">Full Text</a>]
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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Jane Kelly - updated : 12/19/2011
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Jane Kelly - updated : 12/13/2007<br>George E. Tiller - updated : 2/17/2006<br>Jane Kelly - updated : 3/3/2005<br>Jane Kelly - updated : 1/10/2005<br>Cassandra L. Kniffin - updated : 3/2/2004<br>George E. Tiller - updated : 12/3/2002<br>Victor A. McKusick - updated : 1/23/2002<br>Victor A. McKusick - updated : 12/27/2001<br>Victor A. McKusick - updated : 11/30/1999<br>Victor A. McKusick - updated : 9/8/1999<br>Victor A. McKusick - updated : 3/9/1999<br>Victor A. McKusick - updated : 10/26/1998<br>Victor A. McKusick - updated : 5/12/1998<br>Victor A. McKusick - updated : 5/9/1998<br>Victor A. McKusick - updated : 3/31/1998
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Creation Date:
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<span class="mim-text-font">
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Stylianos E. Antonarakis : 1/6/1998
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carol : 06/28/2019
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alopez : 10/17/2016<br>carol : 12/19/2011<br>terry : 3/25/2011<br>carol : 3/24/2011<br>carol : 3/24/2011<br>carol : 3/24/2011<br>carol : 4/3/2009<br>alopez : 2/18/2009<br>wwang : 4/28/2008<br>terry : 4/25/2008<br>carol : 12/13/2007<br>carol : 11/13/2006<br>carol : 9/8/2006<br>wwang : 3/6/2006<br>terry : 2/17/2006<br>tkritzer : 3/3/2005<br>alopez : 1/10/2005<br>terry : 3/19/2004<br>terry : 3/18/2004<br>alopez : 3/17/2004<br>tkritzer : 3/5/2004<br>ckniffin : 3/2/2004<br>cwells : 11/18/2003<br>cwells : 12/3/2002<br>alopez : 1/23/2002<br>carol : 1/9/2002<br>mcapotos : 1/2/2002<br>terry : 12/27/2001<br>alopez : 12/1/1999<br>terry : 11/30/1999<br>terry : 11/30/1999<br>joanna : 10/22/1999<br>carol : 10/15/1999<br>terry : 9/8/1999<br>carol : 3/25/1999<br>terry : 3/25/1999<br>terry : 3/25/1999<br>terry : 3/9/1999<br>terry : 11/18/1998<br>terry : 10/27/1998<br>terry : 10/27/1998<br>terry : 10/26/1998<br>terry : 8/17/1998<br>carol : 5/21/1998<br>joanna : 5/15/1998<br>terry : 5/12/1998<br>carol : 5/9/1998<br>carol : 4/24/1998<br>terry : 4/14/1998<br>alopez : 4/7/1998<br>alopez : 4/2/1998<br>terry : 3/31/1998<br>carol : 1/7/1998<br>carol : 1/6/1998
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<strong>*</strong> 602225
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CONE-ROD HOMEOBOX-CONTAINING GENE; CRX
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<strong><em>HGNC Approved Gene Symbol: CRX</em></strong>
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Cytogenetic location: 19q13.33
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Genomic coordinates <span class="small">(GRCh38)</span> : 19:47,821,937-47,843,324 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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<strong>Gene-Phenotype Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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19q13.33
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Cone-rod retinal dystrophy-2
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<span class="mim-font">
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120970
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Autosomal dominant
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<span class="mim-font">
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3
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Leber congenital amaurosis 7
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<span class="mim-font">
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613829
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<span class="mim-font">
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3
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<strong>TEXT</strong>
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<strong>Cloning and Expression</strong>
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<p>To identify retinal homeobox-containing genes, Freund et al. (1997) screened a human retina cDNA library at low stringency with a fragment from the human CHX10 (142993) cDNA. One of the isolated cDNAs encoded a novel gene, which the authors termed CRX for 'cone-rod homeobox-containing gene.' CRX encodes a 299-amino acid protein with a predicted mass of 32 kD that is most similar to the human OTX1 (600036) and OTX2 (600037) homeodomain proteins. The CRX homeodomain is located near the amino terminus at residues 39 to 99 and belongs to the prd class. Additional domains of the CRX protein include the WSP motif and the OTX tail. The CRX gene was expressed as an abundant 4.5-kb transcript in retina but not in any other of 10 tissues or cells examined. </p><p>Furukawa et al. (1997) isolated the mouse Crx gene from mouse retina. The human CRX cDNA is 97% identical to the mouse gene. Crx expression was restricted to developing and mature photoreceptor cells. Crx bound and transactivated the sequence TAATCC/A, which is found upstream of several photoreceptor-specific genes, including the opsin genes from many species. Overexpression of Crx using a retroviral vector increased the frequency of clones containing exclusively rod photoreceptors and reduced the frequency of clones containing amacrine interneurons and Muller glial cells. In addition, presumptive photoreceptor cells expressing a dominant negative form of Crx failed to form proper photoreceptor outer segments and terminals. The authors concluded that Crx is a photoreceptor-specific transcription factor and plays a crucial role in the differentiation of photoreceptor cells. </p>
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<strong>Gene Function</strong>
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<p>Akagi et al. (2004) reported that CRX and OTX2 effectively induced the generation of photoreceptor-specific phenotypes from ciliary- and iris-derived cells of adult rat. More than 90% of the CRX- and OTX2-transfected ciliary- and iris-derived cells exhibited rod opsin immunoreactivity, whereas few of the similarly transfected mesencephalon-derived neural stem cells from embryonic rat expressed rod opsin. At least 2 additional key components of the phototransduction cascade, recoverin (179618) and G-delta-T1, were expressed by CRX- and OTX2-transfected iris-derived cells. Akagi et al. (2004) concluded that CRX and OTX2 induced phenotype generation in cells derived from iris or ciliary tissue, which may suggest an approach to photoreceptor cell preparation for retinal transplantation. </p><p>Spinocerebellar ataxia type 7 (SCA7; 164500) is an inherited neurodegenerative disorder caused by expansion of a polyglutamine tract in the ataxin-7 (ATXN7; 607640) protein. A unique feature of SCA7 is degeneration of photoreceptor cells in the retina, resulting in cone-rod dystrophy. In an SCA7 transgenic mouse model, La Spada et al. (2001) found that the cone-rod dystrophy involved altered photoreceptor gene expression due to interference with CRX. By coimmunoprecipitation analysis of CRX and ATXN7 truncation and point mutants, Chen et al. (2004) determined that the ATXN7-interacting domain of CRX localized to its glutamine-rich region and that the CRX-interacting domain of ATXN7 localized to its glutamine tract. Nuclear localization of ataxin-7 was required to repress Crx transactivation, and the likely nuclear localization signals were mapped to the C-terminal region of ataxin-7. Using chromatin immunoprecipitation, the authors showed that both Crx and ataxin-7 occupied the promoter and enhancer regions of Crx-regulated retinal genes in vivo. Chen et al. (2004) suggested that one mechanism of SCA7 disease pathogenesis may be transcription dysregulation, and that CRX transcription interference may be a predominant factor in SCA7 cone-rod dystrophy retinal degeneration. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using a combination of in situ hybridization, somatic cell hybrid and radiation hybrid mapping, and yeast artificial chromosome contig analysis, Freund et al. (1997) mapped the CRX gene to 19q13.3 in the interval between markers D19S219 and D19S246 in the critical region of the cone-rod dystrophy-2 locus (CORD2; 120970). </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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<span class="mim-text-font">
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<p>Freund et al. (1997) found a missense and a frameshift mutation in the CRX gene in 2 pedigrees with CORD2 (120970). The authors showed that the missense (602225.0001) mutation was not a polymorphic variant and concluded that mutation in the CRX gene is responsible for the CORD2 phenotype. </p><p>Swain et al. (1997) found an arg41-to-trp substitution in the third residue of the CRX homeodomain in the proband from a family with autosomal dominant CORD. The sequence change cosegregated with the disease phenotype and was not detected in 247 normal controls. The data suggested that mutations in the CRX gene are associated with photoreceptor degeneration and that the Crx protein is necessary for the maintenance of normal cone and rod function. </p><p>Because CRX is essential for photoreceptor maintenance and because expression of a dominant-negative CRX allele in developing retina prevented outer segment biogenesis (Furukawa et al., 1997), Freund et al. (1998) tested the hypothesis that CRX mutations are responsible for some cases of the Leber congenital amaurosis phenotype by examining the CRX gene of 74 Leber congenital amaurosis patients. They identified 2 patients with a de novo deletion mutation (602225.0003-602225.0004, respectively) as the cause of Leber congenital amaurosis-7 (LCA7; 613829). Their findings indicated that the product of the CRX gene is essential not only for normal maintenance of the photoreceptor, as demonstrated by mutations causing autosomal dominant cone-rod dystrophy (120970), but also possibly essential for early photoreceptor development. </p><p>CRX is a transcription factor for several retinal genes, including the opsins and the gene for interphotoreceptor retinoid-binding protein. Because loss of CRX function could alter the expression of a number of other retinal proteins, Sohocki et al. (1998) screened for mutations in the CRX gene in probands with a range of degenerative retinal diseases. Of the 294 unrelated individuals screened, they identified 4 CRX mutations in families with clinical diagnoses of autosomal dominant cone-rod dystrophy, late-onset dominant retinitis pigmentosa, or dominant Leber congenital amaurosis (early-onset retinitis pigmentosa), and they identified 4 additional benign sequence variants. </p><p>Rivolta et al. (2001) summarized 18 mutations in the CRX gene associated with retinal abnormalities. Except for 1 obviously null allele not definitely associated with a phenotype (a frameshift in codon 9), all CRX mutations appeared to be completely penetrant and caused disease in heterozygotes. These dominant alleles fell into 2 categories. In one group were missense mutations and short, in-frame deletions; in the second group were frameshift mutations, all of which were in the last exon. All of these dominant mutations were likely to produce stable mRNA that is translated. Rivolta et al. (2001) did not detect a correlation between type of disease and type of mutation. Four of the mutations were de novo and these were found in isolated cases of Leber congenital amaurosis. Rivolta et al. (2001) noted that dominant CRX mutations have not been associated with mental retardation or developmental delay that has sometimes been found in Leber congenital amaurosis caused by mutation in other genes. </p><p>Chen et al. (2002) used transient transfection and mobility shift assays to investigate the consequences of 11 known mutations in CRX in vitro. They demonstrated that the C-terminal region, between amino acids 200 and 284, is essential for CRX-mediated transcriptional activation. Three homeodomain missense mutations (R41W, 602225.0005; R41Q, 602225.0006; and R90W, 602225.0007) displayed decreased transactivating activity, and E80A (602225.0001) demonstrated markedly increased activity. In vitro protein-DNA binding assays with mutant CRX homeodomain peptides demonstrated that the alteration was due to reduced DNA binding to CRX targets. The authors hypothesized that CRX mutations involved in human photoreceptor degeneration act by impairing CRX-mediated transcriptional regulation of the photoreceptor genes. However, since a clear relationship between the magnitude of biochemical abnormality and degree of disease severity was not observed, the authors suggested that other genetic and environmental modifiers may also contribute to the disease phenotype. </p>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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<p>CRX is expressed not only in the photoreceptors of the retina, but also in the pinealocytes of the pineal gland. Furukawa et al. (1999) generated mice carrying a targeted disruption of Crx. Homozygous deficient mice did not elaborate photoreceptor outer segments and lacked rod and cone activity as assayed by electroretinogram. Expression of several photoreceptor- and pineal-specific genes was reduced in Crx mutants. Circadian entrainment was also affected in Crx -/- mice. To examine photoentrainment activity in homozygous deficient mice, Furukawa et al. (1999) recorded the activity of wildtype and Crx -/- mice running on an exercise wheel. All mice showed robust 24-hour rhythms in activity during entrainment and in constant darkness. All mice showed the most activity during the dark interval of a 24-hour period. The percentage of total activity that occurred at night, however, was significantly less in homozygous deficient mice than in wildtype mice. All mice re-entrained to the light-dark cycle following an advance of 4 hours in the cycle; however, the number of days required to complete the shift was greater in Crx -/- mice. </p><p>Zebrafish proved a useful model for studying circadian gene regulation and pineal organ function. The Crx gene was thought to regulate pineal circadian activity. In the mouse, targeted inactivation of Crx caused a reduction in pineal gene expression and attenuated entrainment to light/dark cycles (Furukawa et al., 1999). Gamse et al. (2002) showed that Crx and Otx5 (orthodenticle homeobox-5) orthologs are expressed in both the pineal organ and the asymmetrically positioned parapineal of larval zebrafish. Circadian gene expression was unaffected by a reduction in Crx expression but was inhibited specifically by depletion of Otx5. These results indicate that Otx5 rather than Crx regulates genes that show circadian expression in the zebrafish pineal complex. </p><p>Using expression studies in transgenic mice under conditional Otx2 (600037) gene ablation, Nishida et al. (2003) presented evidence that Otx2 is a direct upstream regulator of Crx and acts via binding to specific consensus sequences in the Crx promoter. </p><p>Menotti-Raymond et al. (2010) identified a putative mutation in the CRX gene (546delC) as the cause of autosomal dominant rod-cone dysplasia (Rdy) in a pedigree of cats segregating for the disorder. Disease expression in Rdy cats is comparable to that in young patients with Leber congenital amaurosis or retinitis pigmentosa. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>10 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 CONE-ROD DYSTROPHY 2</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CRX, GLU80ALA
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<br />
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SNP: rs104894671,
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ClinVar: RCV000007841, RCV000085995, RCV001386170
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a Greek family with autosomal dominant CORD2 (120970), Freund et al. (1997) identified a GAG-to-GCG mutation at codon 80 of one allele of the CRX gene. The mutation was not a common polymorphism in the Greek population since it was not found in more than 100 normal Greek alleles or in more than 600 other Caucasian control alleles examined. The glu80-to-ala mutation is located within the CRX homeodomain. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 CONE-ROD DYSTROPHY 2</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CRX, 1-BP DEL, 502G
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<br />
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SNP: rs1568626209,
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ClinVar: RCV000007842
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a northern European family with autosomal dominant CORD2 (120970), Freund et al. (1997) identified a deletion of G at nucleotide 502 of one allele of the CRX cDNA (codon 168). This deletion results in a frameshift and premature termination of the CRX protein. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 LEBER CONGENITAL AMAUROSIS 7</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CRX, 2-BP DEL, GLU168
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<br />
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SNP: rs61748446,
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ClinVar: RCV000086005, RCV002274927
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Using SSCP analysis and direct sequencing of PCR-amplified exons of the CRX gene, Freund et al. (1998) identified putative disease-causing de novo deletion mutations in CRX in 2 patients with Leber congenital amaurosis-7 (613829): a 2-bp deletion at the glu168 codon (E168del2bp) and a 1-bp deletion at the gly217 codon (G217del1bp; 602225.0004). Both deletions caused frameshifts, and the predicted proteins lacked the conserved carboxy-terminal tail. The E168del2bp allele had lost an AG dinucleotide from the GAG codon for the eleventh residue within the conserved 13-amino acid WSP motif. If the mRNA containing this premature stop codon were stable, 45% of the protein would be lost and replaced with a new C terminus of 4 amino acids (VPFA). The G217del1bp allele was due to deletion of a G nucleotide, also within a short conserved sequence, and the predicted protein would lack 25% of the C terminus, with 1 new amino acid (alanine) encoded after the frameshift. Curiously, the E168del2bp mutation occurred within the same codon as a mutation found in an autosomal dominant cone-rod dystrophy family (602225.0003). Both E168 and G217 are followed by polypyrimidine runs, a feature commonly associated with deletions. Neither mutation was present in any of the parents or in 360 control CRX alleles. Freund et al. (1998) stated that although they were unable to identify a mutation in the other CRX allele of either patient, both might nevertheless carry a second CRX mutation (such as a promoter or mid-intron mutation) that remains to be discovered. If that is the case, the inheritance would be recessive. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0004 LEBER CONGENITAL AMAUROSIS 7</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CRX, 1-BP DEL, GLY217
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<br />
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SNP: rs281865517,
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ClinVar: RCV000086016, RCV002274928
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>See 602225.0003 and Freund et al. (1998). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 CONE-ROD DYSTROPHY 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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|
|
CRX, ARG41TRP
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<br />
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SNP: rs104894672,
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|
|
gnomAD: rs104894672,
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|
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ClinVar: RCV000007843, RCV000085989, RCV001073396, RCV001386169, RCV003324484, RCV003324485
|
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|
|
</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In the proband from a family with autosomal dominant CORD2 (120970), Swain et al. (1997) found an arg41-to-trp substitution in the third residue of the CRX homeodomain. The substitution caused a decrease in DNA binding activity. The sequence change cosegregated with the disease phenotype and was not detected in 247 normal controls. </p>
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|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 CONE-ROD DYSTROPHY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
CRX, ARG41GLN
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|
<br />
|
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|
|
SNP: rs61748436,
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|
|
|
|
|
gnomAD: rs61748436,
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|
|
|
|
|
ClinVar: RCV000007846, RCV000085990, RCV001059718, RCV001075469, RCV001263020, RCV004755718
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the proband from a family segregating autosomal dominant cone-rod dystrophy-2 (120970), Swain et al. (1997) identified a G-to-A transition in the CRX gene, resulting in an arg41-to-gln (R41Q) substitution. This mutation involves the same codon as the arg41-to-trp mutation (602225.0005) found by Swain et al. (1997) in a patient with autosomal dominant CORD2. </p><p>Sohocki et al. (1998) identified the R41Q mutation in a proband originally diagnosed with late-onset dominant retinitis pigmentosa. The authors stated that later analysis of additional members of this family suggested an alternative diagnosis of late-onset, atypical, cone-rod dystrophy. None of the other 163 probands with a diagnosis of autosomal dominant RP studied by Sohocki et al. (1998) were found to have a mutation in the CRX gene. </p>
|
|
</span>
|
|
</div>
|
|
|
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|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 LEBER CONGENITAL AMAUROSIS 7</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CRX, ARG90TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894673,
|
|
|
|
|
|
gnomAD: rs104894673,
|
|
|
|
|
|
ClinVar: RCV000007847, RCV000086364, RCV001074643, RCV001244346
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Leber congenital amaurosis-7 (613829), Swaroop et al. (1999) identified a homozygous substitution of arginine (arg) at codon 90 by tryptophan (trp) in the CRX homeodomain due to a C-to-T transition in exon 3 of the CRX gene. Swaroop et al. (1999) found that the mutant CRX (R90W) homeodomain demonstrated decreased binding to the previously identified cis sequence elements in the rhodopsin promoter. In transient transfection experiments, the mutant protein showed significantly reduced ability to transactivate the rhodopsin promoter, as well as lower synergistic activation with the transcription factor NRL (162080). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 LEBER CONGENITAL AMAUROSIS 7</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CRX, 1-BP DEL, 520G
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs281865515,
|
|
|
|
|
|
|
|
ClinVar: RCV000007848, RCV000086007
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Nakamura et al. (2002) reported a novel de novo mutation in the CRX gene in a Japanese patient with Leber congenital amaurosis-7 (613829). The CRX gene was analyzed by direct genomic sequencing in the patient with LCA and in his healthy parents. They identified a heterozygous deletion of G at nucleotide 520 in CRX, predicting a frameshift in codon 174 and a premature termination of translation. The mutation was not present in the proband's unaffected parents. Except for CRX, all known genes that cause LCA cause the disorder in an autosomal recessive fashion. This mutation was similar to the other 5 known de novo mutations in CRX because it was a heterozygous deletion of 1 or 2 base pairs in exon 3 causing a frameshift, producing a protein lacking the conserved OTX tail motif near the C terminus. </p>
|
|
</span>
|
|
</div>
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<div>
|
|
<br />
|
|
</div>
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|
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</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 CONE-ROD DYSTROPHY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CRX, 1-BP DEL, 615C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs281865516,
|
|
|
|
|
|
gnomAD: rs281865516,
|
|
|
|
|
|
ClinVar: RCV000007849, RCV000086015, RCV001854501, RCV003888488
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 3-generation Japanese family with cone-rod dystrophy (CORD; 120970), Itabashi et al. (2004) identified a heterozygous deletion of a cytidine at nucleotide 615 in exon 1 of the CRX gene (605delC). Ophthalmic findings included negative-type electroretinogram and rapid progression after age 40 years. </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>.0010 CONE-ROD DYSTROPHY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
CRX, 3-BP DEL/2-BP INS, NT816
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs2123743692,
|
|
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|
|
|
|
|
ClinVar: RCV000007850, RCV004814856
|
|
|
|
|
|
</span>
|
|
</div>
|
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|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 2-generation German family with cone-rod dystrophy (CORD2; 120970), Paunescu et al. (2007) identified a novel heterozygous complex mutation (816delCACinsAA) in the CRX gene, predicting the substitution of 27 C-terminal amino acids by 44 novel amino acids. </p>
|
|
</span>
|
|
</div>
|
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
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|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Akagi, T., Mandai, M., Ooto, S., Hirami, Y., Osakada, F., Kageyama, R., Yoshimura, N., Takahashi, M.
|
|
<strong>Otx2 homeobox gene induces photoreceptor-specific phenotypes in cells derived from adult iris and ciliary tissue.</strong>
|
|
Invest. Ophthal. Vis. Sci. 45: 4570-4575, 2004.
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|
|
[PubMed: 15557469]
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|
[Full Text: https://doi.org/10.1167/iovs.04-0697]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Chen, S., Peng, G.-H., Wang, X., Smith, A. C., Grote, S. K., Sopher, B. L., La Spada, A. R.
|
|
<strong>Interference of Crx-dependent transcription by ataxin-7 involves interaction between the glutamine regions and requires the ataxin-7 carboxy-terminal region for nuclear localization.</strong>
|
|
Hum. Molec. Genet. 13: 53-67, 2004.
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|
[PubMed: 14613968]
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|
[Full Text: https://doi.org/10.1093/hmg/ddh005]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Chen, S., Wang, Q.-L., Xu, S., Liu, I., Li, L. Y., Wang, Y., Zack, D. J.
|
|
<strong>Functional analysis of cone-rod homeobox (CRX) mutations associated with retinal dystrophy.</strong>
|
|
Hum. Molec. Genet. 11: 873-884, 2002.
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|
[PubMed: 11971869]
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|
[Full Text: https://doi.org/10.1093/hmg/11.8.873]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Freund, C. L., Gregory-Evans, C. Y., Furukawa, T., Papaioannou, M., Looser, J., Ploder, L., Bellingham, J., Ng, D., Herbrick, J. A., Duncan, A., Scherer, S. W., Tsui, L. C., Loutradis-Anagnostou, A., Jacobson, S. G., Cepko, C. L., Bhattacharya, S. S., McInnes, R. R.
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