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Entry
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- *604210 - CRUMBS CELL POLARITY COMPLEX COMPONENT 1; CRB1
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- OMIM
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</ul>
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</nav>
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<div id="mimSearch" class="hidden-print">
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<div class="container">
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<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchStart" name="start" value="1" />
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<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
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<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
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<div class="row">
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<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
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<div class="form-group">
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<div class="input-group">
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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<div class="input-group-btn">
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<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
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<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
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<ul class="dropdown-menu dropdown-menu-right">
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<li class="dropdown-header">
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Advanced Search
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/entry"> OMIM </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/geneMap"> Gene Map </a>
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<li role="separator" class="divider"></li>
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<li>
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<a href="/history"> Search History </a>
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</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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</form>
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<p />
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</div>
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<div id="mimAlertBanner">
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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">*604210</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="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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</li>
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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/604210">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">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
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</a>
|
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</span>
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</span>
|
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</div>
|
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000134376;t=ENST00000367400" 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=23418" 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=604210" 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=ENSG00000134376;t=ENST00000367400" 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_001193640,NM_001257965,NM_001257966,NM_201253,NR_047563,NR_047564,XM_011509365,XM_011509367,XM_011509369,XM_017000852,XM_047416572,XM_047416573,XM_047416574,XM_047416575" 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_201253" 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=604210" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
|
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</div>
|
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</div>
|
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
|
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</a>
|
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</span>
|
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</span>
|
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</div>
|
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=05019&isoform_id=05019_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/CRB1" 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/6014482,18175284,18175289,18175295,34364816,41327708,57283951,62087426,71153499,119611683,158260489,221042680,221042682,221044266,221044270,223459574,302370926,384081579,384081581,444733507,767908866,767908870,767908874,1034557193,1880321577,1880321579,1880321581,2217265990,2217265992,2217265995,2217265997,2462507234,2462507236,2462507238,2462507240,2462507242,2462507244,2462507246,2462507248" 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/P82279" 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=23418" 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=ENSG00000134376;t=ENST00000367400" 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=CRB1" 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=CRB1" 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+23418" 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/CRB1" 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:23418" 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/23418" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr1&hgg_gene=ENST00000843830.1&hgg_start=197201504&hgg_end=197478455&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://medlineplus.gov/genetics/gene/crb1" 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=604210[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=604210[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/CRB1/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/ENSG00000134376" 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=CRB1" 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=CRB1" 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=CRB1" 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/crb1mut.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=CRB1&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/PA26863" 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:2343" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0259685.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:2136343" 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/CRB1#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:2136343" 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/23418/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=23418" 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=WBGene00000792;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-050208-382" 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://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:23418" 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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<div><a href="https://reactome.org/content/query?q=CRB1&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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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 723450004<br />
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">ICD+</a>
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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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604210
|
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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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CRUMBS CELL POLARITY COMPLEX COMPONENT 1; CRB1
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</span>
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</h3>
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</div>
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<div>
|
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
|
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<em>Alternative titles; symbols</em>
|
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</span>
|
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</p>
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
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CRUMBS, DROSOPHILA, HOMOLOG OF, 1
|
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</span>
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=CRB1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CRB1</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/1/1536?start=-3&limit=10&highlight=1536">1q31.3</a>
|
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:197201504-197478455&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">1:197,201,504-197,478,455</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>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
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</div>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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Phenotype
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<a href="/clinicalSynopsis/table?mimNumber=613835,172870,600105" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
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View Clinical Synopses
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Phenotype <br /> MIM number
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1q31.3
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Leber congenital amaurosis 8
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<a href="/entry/613835"> 613835 </a>
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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Pigmented paravenous chorioretinal atrophy
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<a href="/entry/172870"> 172870 </a>
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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Retinitis pigmentosa-12
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<a href="/entry/600105"> 600105 </a>
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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PheneGene Graphics <span class="caret"></span>
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<li><a href="/graph/linear/604210" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/604210" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<strong>Cloning and Expression</strong>
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<p>To isolate candidate genes for chorioretinal diseases, <a href="#10" class="mim-tip-reference" title="den Hollander, A. I., van Driel, M. A., de Kok, Y. J. M., van de Pol, D. J. R., Hoyng, C. B., Brunner, H. G., Deutman, A. F., Cremers, F. P. M. <strong>Isolation and mapping of novel candidate genes for retinal disorders using suppression subtractive hybridization.</strong> Genomics 58: 240-249, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10373321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10373321</a>] [<a href="https://doi.org/10.1006/geno.1999.5823" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10373321">den Hollander et al. (1999)</a> cloned cDNAs specifically or preferentially expressed in the human retina and the retinal pigment epithelium (RPE) through a novel suppression subtractive hybridization (SSH) method (<a href="#11" class="mim-tip-reference" title="Diatchenko, L., Lau, Y.-F. C., Campbell, A. P., Chenchik, A., Moqadam, F., Huang, B., Lukyanov, S., Lukyanov, K., Gurskaya, N., Sverdlov, E. D., Siebert, P. D. <strong>Suppression subtractive hybridization: a method for generating differentially regulated or tissue-specific cDNA probes and libraries.</strong> Proc. Nat. Acad. Sci. 93: 6025-6030, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8650213/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8650213</a>] [<a href="https://doi.org/10.1073/pnas.93.12.6025" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8650213">Diatchenko et al., 1996</a>). One of these cDNAs (RET3C11) mapped to 1q31-q32.1, a region harboring a gene involved in a severe form of autosomal recessive retinitis pigmentosa characterized by a typical preservation of the paraarteriolar RPE, designated RP12 (<a href="/entry/600105">600105</a>). <a href="#9" class="mim-tip-reference" title="den Hollander, A. I., ten Brink, J. B., de Kok, Y. J. M., van Soest, S., van den Born, L. I., van Driel, M. A., van de Pol, D. J. R., Payne, A. M., Bhattacharya, S. S., Kellner, U., Hoyng, C. B., Westerveld, A., Brunner, H. G., Bleeker-Wagemakers, E. M., Deutman, A. F., Heckenlively, J. R., Cremers, F. P. M., Bergen, A. A. B. <strong>Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12).</strong> Nature Genet. 23: 217-221, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10508521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10508521</a>] [<a href="https://doi.org/10.1038/13848" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10508521">Den Hollander et al. (1999)</a> isolated the full-length cDNA, encoding an extracellular protein with 19 EGF-like domains, 3 laminin-A G-like domains, and a C-type lectin domain. This 1,376-amino acid protein, 35% identical to the protein 'crumbs' (CRB) of Drosophila melanogaster, was denoted CRB1 for crumbs homolog-1. The CRB1 gene consists of 11 exons and spans at least 40 kb. Northern blot analysis detected a 5-kb transcript in neural retina; RT-PCR detected expression additionally in adult and fetal brain. The similarity to Drosophila CRB suggested a role for CRB1 in cell-cell interaction and possibly in the maintenance of cell polarity in the retina. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10508521+8650213+10373321" 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="#21" class="mim-tip-reference" title="Roh, M. H., Makarova, O., Liu, C.-J., Shin, K., Lee, S., Laurinec, S., Goyal, M., Wiggins, R., Margolis, B. <strong>The Maguk protein, Pals1, functions as an adapter, linking mammalian homologues of Crumbs and Discs Lost.</strong> J. Cell Biol. 157: 161-172, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11927608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11927608</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11927608[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1083/jcb.200109010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11927608">Roh et al. (2002)</a> obtained a full-length cDNA encoding CRB1. The protein contains a transmembrane segment and a 37-amino acid tail. It is associated in tight junctions with MPP5 (<a href="/entry/606958">606958</a>) and PATJ (<a href="/entry/603199">603199</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11927608" 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>Gene Function</strong>
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<p>The polarized architecture of epithelial cells depends on the highly stereotypic distribution of cellular junctions and other membrane-associated protein complexes. In epithelial cells of the Drosophila embryo, 3 distinct domains subdivide the lateral plasma membrane. The most apical one comprises the subapical complex. It is followed by the zonula adherens, and, further basally, by the septate junction. A core component of the subapical complex is the transmembrane protein crumbs, the cytoplasmic domain of which recruits the PDZ protein Patj (<a href="/entry/603199">603199</a>) into the complex. Cells lacking crumbs or the functionally related gene 'stardust' fail to organize a continuous zonular adherens and to maintain cell polarity. <a href="#2" class="mim-tip-reference" title="Bachmann, A., Schneider, M., Theilenberg, E., Grawe, F., Knust, E. <strong>Drosophila stardust is a partner of crumbs in the control of epithelial cell polarity.</strong> Nature 414: 638-643, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11740560/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11740560</a>] [<a href="https://doi.org/10.1038/414638a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11740560">Bachmann et al. (2001)</a> demonstrated that stardust provides an essential component of the subapical complex. Stardust proteins colocalize with crumbs and bind to the carboxy-terminal amino acids of its cytoplasmic tail. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11740560" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Pellikka, M., Tanentzapf, G., Pinto, M., Smith, C., McGlade, C. J., Ready, D. F., Tepass, U. <strong>Crumbs, the Drosophila homologue of human CRB1/RP12, is essential for photoreceptor morphogenesis.</strong> Nature 416: 143-149, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11850625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11850625</a>] [<a href="https://doi.org/10.1038/nature721" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11850625">Pellikka et al. (2002)</a> showed that crumbs and CRB1 localize to corresponding subdomains of the photoreceptor apical plasma membrane: the stalk of the Drosophila photoreceptor and the inner segment of mammalian photoreceptors. The subdomains support the morphogenesis and orientation of the photosensitive membrane organelles: rhabdomeres and outer segments, respectively. Drosophila crumbs is required to maintain zonula adherens integrity during the rapid apical membrane expansion that builds the rhabdomere. Crumbs also regulates stalk development by stabilizing the membrane-associated spectrin cytoskeleton, a function mechanistically distinct from its role in epithelial apical-basal polarity. <a href="#20" class="mim-tip-reference" title="Pellikka, M., Tanentzapf, G., Pinto, M., Smith, C., McGlade, C. J., Ready, D. F., Tepass, U. <strong>Crumbs, the Drosophila homologue of human CRB1/RP12, is essential for photoreceptor morphogenesis.</strong> Nature 416: 143-149, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11850625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11850625</a>] [<a href="https://doi.org/10.1038/nature721" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11850625">Pellikka et al. (2002)</a> proposed that crumbs is a central component of a molecular scaffold that controls zonula adherens assembly and defines the stalk as an apical membrane subdomain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11850625" 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="Izaddoost, S., Nam, S.-C., Bhat, M. A., Bellen, H. J., Choi, K.-W. <strong>Drosophila crumbs is a positional cue in photoreceptor adherens junctions and rhabdomeres.</strong> Nature 416: 178-182, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11850624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11850624</a>] [<a href="https://doi.org/10.1038/nature720" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11850624">Izaddoost et al. (2002)</a> described the properties of crumbs that control the position and integrity of the photoreceptor adherens junction and photosensitive organ, or rhabdomere, in Drosophila. In contrast to normal photoreceptor adherens junctions and rhabdomeres, which span the depth of the retina, adherens junctions and rhabdomeres of crumbs-deficient photoreceptors initially accumulate at the top of the retina and fail to maintain their integrity as they stretch to the retinal floor. <a href="#15" class="mim-tip-reference" title="Izaddoost, S., Nam, S.-C., Bhat, M. A., Bellen, H. J., Choi, K.-W. <strong>Drosophila crumbs is a positional cue in photoreceptor adherens junctions and rhabdomeres.</strong> Nature 416: 178-182, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11850624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11850624</a>] [<a href="https://doi.org/10.1038/nature720" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11850624">Izaddoost et al. (2002)</a> showed that crumbs controls localization of the adherens junction through its intracellular domain containing a putative binding site for a protein 4.1 superfamily protein (FERM). Although loss of crumbs or overexpression of the FERM binding domain caused mislocalization of adherens junctions, they did not result in a significant loss of photoreceptor polarity. The intracellular domain of human CRB1 behaved similarly to its Drosophila counterpart when overexpressed in the fly eye. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11850624" 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 striking difference between CRB1 and crumbs is that the latter contains a transmembrane region and a 37-amino acid cytoplasmic domain. <a href="#8" class="mim-tip-reference" title="den Hollander, A. I., Johnson, K., de Kok, Y. J. M., Klebes, A., Brunner, H. G., Knust, E., Cremers, F. P. M. <strong>CRB1 has a cytoplasmic domain that is functionally conserved between human and Drosophila.</strong> Hum. Molec. Genet. 10: 2767-2773, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11734541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11734541</a>] [<a href="https://doi.org/10.1093/hmg/10.24.2767" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11734541">Den Hollander et al. (2001)</a> described an alternative splice variant of human CRB1 that encodes a cytoplasmic domain 72% similar to that of Drosophila crumbs. Two intracellular subdomains that are necessary for function in Drosophila are absolutely conserved. Rescuing and overexpression studies in Drosophila showed that the cytoplasmic domains are functionally related between these distant species. The authors hypothesized that CRB1 may organize an intracellular protein scaffold in the human retina. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11734541" 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="Jacobson, S. G., Cideciyan, A. V., Aleman, T. S., Pianta, M. J., Sumaroka, A., Schwartz, S. B., Smilko, E. E., Milam, A. H., Sheffield, V. C., Stone, E. M. <strong>Crumbs homolog 1 (CRB1) mutations result in a thick human retina with abnormal lamination.</strong> Hum. Molec. Genet. 12: 1073-1078, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12700176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12700176</a>] [<a href="https://doi.org/10.1093/hmg/ddg117" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12700176">Jacobson et al. (2003)</a> characterized the retinal organization in vivo of patients with CRB1 mutations and found that, unlike other inherited retinal degenerations, the CRB1 mutant retinas were remarkably thick in cross-section and lacked the distinct layers of normal adult retina. There were coarse outer and inner zones and a thick surface layer around the optic nerve. The abnormal retinal architecture in CRB1 mutations resembled that of immature normal retina. <a href="#16" class="mim-tip-reference" title="Jacobson, S. G., Cideciyan, A. V., Aleman, T. S., Pianta, M. J., Sumaroka, A., Schwartz, S. B., Smilko, E. E., Milam, A. H., Sheffield, V. C., Stone, E. M. <strong>Crumbs homolog 1 (CRB1) mutations result in a thick human retina with abnormal lamination.</strong> Hum. Molec. Genet. 12: 1073-1078, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12700176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12700176</a>] [<a href="https://doi.org/10.1093/hmg/ddg117" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12700176">Jacobson et al. (2003)</a> concluded that the CRB1 disease pathway disturbs the development of normal human retinal organization by interrupting naturally occurring apoptosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12700176" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#6" class="mim-tip-reference" title="den Hollander, A. I., Davis, J., van der Velde-Visser, S. D., Zonneveld, M. N., Pierrottet, C. O., Koenekoop, R. K., Kellner, U., van den Born, L. I., Heckenlively, J. R., Hoyng, C. B., Handford, P. A., Roepman, R., Cremers, F. P. M. <strong>CRB1 mutation spectrum in inherited retinal dystrophies.</strong> Hum. Mutat. 24: 355-369, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15459956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15459956</a>] [<a href="https://doi.org/10.1002/humu.20093" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15459956">Den Hollander et al. (2004)</a> stated that 71 different sequence variants had been identified in the CRB1 gene in patients with retinal dystrophies. They provided an overview of currently known CRB1 variants and discussed their effects. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15459956" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Henderson, R. H., Mackay, D. S., Li, Z., Moradi, P., Sergouniotis, P., Russell-Eggitt, I., Thompson, D. A., Robson, A. G., Holder, G. E., Webster, A. R., Moore, A. T. <strong>Phenotypic variability in patients with retinal dystrophies due to mutations in CRB1.</strong> Brit. J. Ophthal. 95: 811-817, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20956273/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20956273</a>] [<a href="https://doi.org/10.1136/bjo.2010.186882" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20956273">Henderson et al. (2011)</a> sought to identify CRB1 mutations in a large cohort of patients with recessive retinal dystrophies and to document the retinal phenotype and visual prognosis. They recruited 306 patients with Leber congenital amaurosis (LCA), early-onset childhood retinal dystrophy, or juvenile-onset retinitis pigmentosa to the study. Mutations in CRB1, including 17 novel mutations, were identified in 41 patients from 32 families, and those patients underwent detailed phenotyping. Common phenotypic features included hypermetropic refractive error, nummular pigmentation at the level of the retinal pigment epithelium (RPE), and increased retinal thickness on optical coherence tomography (OCT). Most patients had a clinical and electrophysiologic phenotype consistent with a diagnosis of LCA or rod-cone dystrophy, but 3 patients had electroretinogram evidence of cone-rod degeneration. A minority of patients developed peripheral retinal telangiectasia, which in some cases led to seclusio pupillae and angle-closure glaucoma. <a href="#14" class="mim-tip-reference" title="Henderson, R. H., Mackay, D. S., Li, Z., Moradi, P., Sergouniotis, P., Russell-Eggitt, I., Thompson, D. A., Robson, A. G., Holder, G. E., Webster, A. R., Moore, A. T. <strong>Phenotypic variability in patients with retinal dystrophies due to mutations in CRB1.</strong> Brit. J. Ophthal. 95: 811-817, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20956273/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20956273</a>] [<a href="https://doi.org/10.1136/bjo.2010.186882" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20956273">Henderson et al. (2011)</a> concluded that mutations in CRB1 were associated with a range of recessively inherited retinal dystrophies, including LCA and childhood- and juvenile-onset rod-cone and cone-rod dystrophy. Although the phenotype was usually severe, in milder cases there was a window of opportunity for therapeutic intervention in early childhood. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20956273" 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="#5" class="mim-tip-reference" title="Bujakowska, K., Audo, I., Mohand-Said, S., Lancelot, M.-E., Antonio, A., Germain, A., Leveillard, T., Letexier, M., Saraiva, J.-P., Lonjou, C., Carpentier, W., Sahel, J.-A., Bhattacharya, S. S., Zeitz, C. <strong>CRB1 mutations in inherited retinal dystrophies.</strong> Hum. Mutat. 33: 306-315, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22065545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22065545</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22065545[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.21653" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22065545">Bujakowska et al. (2012)</a> analyzed the CRB1 gene in 400 index patients with a provisional diagnosis of retinitis pigmentosa and identified 11 patients carrying likely pathogenic variants of CRB1. Analysis of the more than 150 previously reported CRB1 mutations and the clinical features of the respective patients showed that no specific allele combination could be assigned to a particular phenotype. <a href="#5" class="mim-tip-reference" title="Bujakowska, K., Audo, I., Mohand-Said, S., Lancelot, M.-E., Antonio, A., Germain, A., Leveillard, T., Letexier, M., Saraiva, J.-P., Lonjou, C., Carpentier, W., Sahel, J.-A., Bhattacharya, S. S., Zeitz, C. <strong>CRB1 mutations in inherited retinal dystrophies.</strong> Hum. Mutat. 33: 306-315, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22065545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22065545</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22065545[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.21653" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22065545">Bujakowska et al. (2012)</a> suggested that the modulation of phenotype in patients with CRB1 mutations is due to additional modifying factors, genetic and/or environmental. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22065545" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Retinitis Pigmentosa 12</em></strong></p><p>
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In 10 unrelated RP12 (<a href="/entry/600105">600105</a>) patients, <a href="#9" class="mim-tip-reference" title="den Hollander, A. I., ten Brink, J. B., de Kok, Y. J. M., van Soest, S., van den Born, L. I., van Driel, M. A., van de Pol, D. J. R., Payne, A. M., Bhattacharya, S. S., Kellner, U., Hoyng, C. B., Westerveld, A., Brunner, H. G., Bleeker-Wagemakers, E. M., Deutman, A. F., Heckenlively, J. R., Cremers, F. P. M., Bergen, A. A. B. <strong>Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12).</strong> Nature Genet. 23: 217-221, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10508521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10508521</a>] [<a href="https://doi.org/10.1038/13848" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10508521">den Hollander et al. (1999)</a> identified a homozygous AluY insertion disrupting the open reading frame, 5 homozygous missense mutations, and 4 compound heterozygous mutations in the CRB1 gene. The distinct RPE abnormalities observed in RP12 patients suggested that CRB1 mutations trigger a novel mechanism of photoreceptor degeneration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10508521" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="den Hollander, A. I., Heckenlively, J. R., van den Born, L. I., de Kok, Y. J. M., van der Velde-Visser, S. D., Kellner, U., Jurklies, B., van Schooneveld, M. J., Blankenagel, A., Rohrschneider, K., Wissinger, B., Cruysberg, J. R. M., Deutman, A. F., Brunner, H. G., Apfelstedt-Sylla, E., Hoyng, C. B., Cremers, F. P. M. <strong>Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the Crumbs homologue 1 (CRB1) gene.</strong> Am. J. Hum. Genet. 69: 198-203, 2001. Note: Erratum: Am. J. Hum. Genet. 69: 1160 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11389483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11389483</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11389483[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/321263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11389483">Den Hollander et al. (2001)</a> identified CRB1 mutations in 5 of 9 patients who had RP with Coats-like exudative vasculopathy, a relatively rare complication of RP that may progress to partial or total retinal detachment. Given that 4 of 5 patients had developed the complication in one eye and that not all sibs with RP have the complication, <a href="#7" class="mim-tip-reference" title="den Hollander, A. I., Heckenlively, J. R., van den Born, L. I., de Kok, Y. J. M., van der Velde-Visser, S. D., Kellner, U., Jurklies, B., van Schooneveld, M. J., Blankenagel, A., Rohrschneider, K., Wissinger, B., Cruysberg, J. R. M., Deutman, A. F., Brunner, H. G., Apfelstedt-Sylla, E., Hoyng, C. B., Cremers, F. P. M. <strong>Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the Crumbs homologue 1 (CRB1) gene.</strong> Am. J. Hum. Genet. 69: 198-203, 2001. Note: Erratum: Am. J. Hum. Genet. 69: 1160 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11389483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11389483</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11389483[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/321263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11389483">den Hollander et al. (2001)</a> suggested that CRB1 mutations should be considered an important risk factor for the Coats-like reaction, although its development may require additional genetic or environmental factors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11389483" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a consanguineous family with early-onset retinitis pigmentosa, <a href="#3" class="mim-tip-reference" title="Benayoun, L., Spiegel, R., Auslender, N., Abbasi, A. H., Rizel, L., Hujeirat, Y., Salama, I., Garzozi, H. J., Allon-Shalev, S., Ben-Yosef, T. <strong>Genetic heterogeneity in two consanguineous families segregating early onset retinal degeneration: the pitfalls of homozygosity mapping.</strong> Am. J. Med. Genet. 149A: 650-656, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19140180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19140180</a>] [<a href="https://doi.org/10.1002/ajmg.a.32634" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19140180">Benayoun et al. (2009)</a> identified compound heterozygosity for a G1103R mutation (<a href="#0011">604210.0011</a>) and a 10-bp deletion (<a href="#0012">604210.0012</a>) in the CRB1 gene. Each mutation had previously been identified in homozygosity in a family diagnosed with Leber congenital amaurosis (LCA8; <a href="/entry/613835">613835</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19140180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Leber Congenital Amaurosis 8</em></strong></p><p>
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<a href="#17" class="mim-tip-reference" title="Lotery, A. J., Jacobson, S. G., Fishman, G. A., Weleber, R. G., Fulton, A. B., Namperumalsamy, P., Heon, E., Levin, A. V., Grover, S., Rosenow, J. R., Kopp, K. K., Sheffield, V. C., Stone, E. M. <strong>Mutations in the CRB1 gene cause Leber congenital amaurosis.</strong> Arch. Ophthal. 119: 415-420, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11231775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11231775</a>] [<a href="https://doi.org/10.1001/archopht.119.3.415" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11231775">Lotery et al. (2001)</a> screened the candidate gene CRB1 in 190 patients with Leber congenital amaurosis (LCA8; <a href="/entry/613835">613835</a>) who were negative for mutation in 6 known LCA genes and 140 controls, and identified 21 patients and 2 controls who harbored amino acid-altering sequence variants (p = 0.03; see, e.g., <a href="#0013">604210.0013</a>). The authors noted that the 21 CRB1 mutation-carrying patients represented 9% of their total cohort of 233 LCA patients, making CRB1 the most commonly mutated gene in this group of patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11231775" 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 of the early onset of disease in patients who have retinal pigmentosa with preserved paraarteriolar retinal pigment epithelium (RP12), with severe loss of vision at ages of less than 20 years, <a href="#7" class="mim-tip-reference" title="den Hollander, A. I., Heckenlively, J. R., van den Born, L. I., de Kok, Y. J. M., van der Velde-Visser, S. D., Kellner, U., Jurklies, B., van Schooneveld, M. J., Blankenagel, A., Rohrschneider, K., Wissinger, B., Cruysberg, J. R. M., Deutman, A. F., Brunner, H. G., Apfelstedt-Sylla, E., Hoyng, C. B., Cremers, F. P. M. <strong>Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the Crumbs homologue 1 (CRB1) gene.</strong> Am. J. Hum. Genet. 69: 198-203, 2001. Note: Erratum: Am. J. Hum. Genet. 69: 1160 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11389483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11389483</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11389483[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/321263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11389483">den Hollander et al. (2001)</a> considered CRB1 to be a good candidate gene for Leber congenital amaurosis. They detected mutations in CRB1 in 7 (13%) of 52 patients with LCA from the Netherlands, Germany, and the United States (see, e.g., <a href="#0006">604210.0006</a>-<a href="#0007">604210.0007</a>). Although no clear-cut genotype-phenotype correlation could be established, <a href="#7" class="mim-tip-reference" title="den Hollander, A. I., Heckenlively, J. R., van den Born, L. I., de Kok, Y. J. M., van der Velde-Visser, S. D., Kellner, U., Jurklies, B., van Schooneveld, M. J., Blankenagel, A., Rohrschneider, K., Wissinger, B., Cruysberg, J. R. M., Deutman, A. F., Brunner, H. G., Apfelstedt-Sylla, E., Hoyng, C. B., Cremers, F. P. M. <strong>Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the Crumbs homologue 1 (CRB1) gene.</strong> Am. J. Hum. Genet. 69: 198-203, 2001. Note: Erratum: Am. J. Hum. Genet. 69: 1160 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11389483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11389483</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11389483[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/321263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11389483">den Hollander et al. (2001)</a> found that patients with LCA, which is the most severe retinal dystrophy, carried null alleles more frequently than did patients with retinitis pigmentosa. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11389483" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In all 4 affected members of a Middle Eastern family with LCA8 and high to extreme hyperopia, <a href="#1" class="mim-tip-reference" title="Abouzeid, H., Li, Y., Maumenee, I. H., Dharmaraj, S., Sundlin, O. <strong>A G1103R mutation in CRB1 is co-inherited with high hyperopia and Leber congenital amaurosis.</strong> Ophthalmic Genet. 27: 15-20, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16543197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16543197</a>] [<a href="https://doi.org/10.1080/13816810500481840" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16543197">Abouzeid et al. (2006)</a> found linkage of the disorder to 1q31 and identified homozygosity for a mutation in the CRB1 gene (G1103R; <a href="#0011">604210.0011</a>). <a href="#1" class="mim-tip-reference" title="Abouzeid, H., Li, Y., Maumenee, I. H., Dharmaraj, S., Sundlin, O. <strong>A G1103R mutation in CRB1 is co-inherited with high hyperopia and Leber congenital amaurosis.</strong> Ophthalmic Genet. 27: 15-20, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16543197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16543197</a>] [<a href="https://doi.org/10.1080/13816810500481840" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16543197">Abouzeid et al. (2006)</a> showed that hyperopia and LCA were linked to the mutant CRB1 gene itself and were not dependent on unlinked modifiers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16543197" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Pigmented Paravenous Chorioretinal Atrophy</em></strong></p><p>
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In all 6 affected members of a family segregating pigmented paravenous chorioretinal atrophy (PPCRA; <a href="/entry/172870">172870</a>), <a href="#18" class="mim-tip-reference" title="McKay, G. J., Clarke, S., Davis, J. A., Simpson, D. A. C., Silvestri, G. <strong>Pigmented paravenous chorioretinal atrophy is associated with a mutation within the crumbs homolog 1 (CRB1) gene.</strong> Invest. Ophthal. Vis. Sci. 46: 322-328, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15623792/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15623792</a>] [<a href="https://doi.org/10.1167/iovs.04-0734" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15623792">McKay et al. (2005)</a> identified heterozygosity for a val162-to-met (V162M; <a href="#0010">604210.0010</a>) mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15623792" 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="#19" class="mim-tip-reference" title="Mehalow, A. K., Kameya, S., Smith, R. S., Hawes, N. L., Denegre, J. M., Young, J. A., Bechtold, L., Haider, N. B., Tepass, U., Heckenlively, J. R., Chang, B., Naggert, J. K., Nishina, P. M. <strong>CRB1 is essential for external limiting membrane integrity and morphogenesis in the mammalian retina.</strong> Hum. Molec. Genet. 12: 2179-2189, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12915475/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12915475</a>] [<a href="https://doi.org/10.1093/hmg/ddg232" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12915475">Mehalow et al. (2003)</a> identified a mouse model, retinal degeneration-8 (rd8), with a single base deletion in the Crb1 gene. The mutation was predicted to cause a frameshift and premature stop codon with loss of the transmembrane and cytoplasmic domains of CRB1. Similar to Drosophila crumbs (crb) mutants, staining for adherens junction proteins was discontinuous and fragmented. Shortened photoreceptor inner and outer segments were observed as early as 2 weeks after birth, suggesting a developmental defect in these structures rather than a degenerative process. Photoreceptor degeneration was observed only within regions of retinal spotting. Since photoreceptor dysplasia and degeneration in Crb1 mouse mutants strongly varied with genetic background, the authors suggested that the variable phenotypes of human patients with CRB1 mutations may be due to interactions with background modifiers in addition to allelic variations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12915475" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a patient with retinitis pigmentosa with paraarteriolar preservation of retinal pigment epithelium (RP12; <a href="/entry/600105">600105</a>), <a href="#9" class="mim-tip-reference" title="den Hollander, A. I., ten Brink, J. B., de Kok, Y. J. M., van Soest, S., van den Born, L. I., van Driel, M. A., van de Pol, D. J. R., Payne, A. M., Bhattacharya, S. S., Kellner, U., Hoyng, C. B., Westerveld, A., Brunner, H. G., Bleeker-Wagemakers, E. M., Deutman, A. F., Heckenlively, J. R., Cremers, F. P. M., Bergen, A. A. B. <strong>Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12).</strong> Nature Genet. 23: 217-221, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10508521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10508521</a>] [<a href="https://doi.org/10.1038/13848" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10508521">den Hollander et al. (1999)</a> found a homozygous insertion of an Alu repeat DNA element in exon 7 at nucleotide 2320 of the CRB1 cDNA. The Alu element belonged to the AluY subfamily, was oriented in the antisense direction, contained a more than 70-nucleotide poly(A) tail, and was flanked by a 12-bp direct repeat consisting of CRB1 nucleotides 2309-2320. This insertion was present in heterozygous state in the unrelated parents and in 2 sibs of the patient, but not in 185 healthy controls. The Alu sequence showed a 5-prime truncation that was also observed in a pathologic Alu element inserted in the F9 gene of hemophilia B (<a href="#22" class="mim-tip-reference" title="Vidaud, D., Vidaud, M., Bahnak, B. R., Siguret, V., Sanchez, S. G., Laurian, Y., Meyer, D., Goossens, M., Lavergne, J. M. <strong>Haemophilia B due to a de novo insertion of a human-specific Alu subfamily member within the coding region of the factor IX gene.</strong> Europ. J. Hum. Genet. 1: 30-36, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8069649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8069649</a>] [<a href="https://doi.org/10.1159/000472385" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8069649">Vidaud et al., 1993</a>); see <a href="/entry/300746#0098">300746.0098</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10508521+8069649" 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> rs62635656 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs62635656;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/rs62635656?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=rs62635656" 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=rs62635656" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a patient with retinitis pigmentosa-12 (RP12; <a href="/entry/600105">600105</a>), <a href="#9" class="mim-tip-reference" title="den Hollander, A. I., ten Brink, J. B., de Kok, Y. J. M., van Soest, S., van den Born, L. I., van Driel, M. A., van de Pol, D. J. R., Payne, A. M., Bhattacharya, S. S., Kellner, U., Hoyng, C. B., Westerveld, A., Brunner, H. G., Bleeker-Wagemakers, E. M., Deutman, A. F., Heckenlively, J. R., Cremers, F. P. M., Bergen, A. A. B. <strong>Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12).</strong> Nature Genet. 23: 217-221, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10508521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10508521</a>] [<a href="https://doi.org/10.1038/13848" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10508521">den Hollander et al. (1999)</a> observed a homozygous nonconservative met1041-to-thr (M1041T) mutation in the CRB1 gene. This patient was from the family described by <a href="#4" class="mim-tip-reference" title="Bleeker-Wagemakers, L. M., Gal, A., Kumar-Singh, R., van den Born, L. I., Li, Y., Schwinger, E., Sandkuijl, L. A., Bergen, A. A. B., Kenna, P., Humphries, P., Farrar, G. J. <strong>Evidence for nonallelic genetic heterogeneity in autosomal recessive retinitis pigmentosa.</strong> Genomics 14: 811-812, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1427914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1427914</a>] [<a href="https://doi.org/10.1016/s0888-7543(05)80195-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1427914">Bleeker-Wagemakers et al. (1992)</a> in which the RP12 locus was originally mapped. The same mutation was found in heterozygosity in 1 of 100 healthy control individuals living in the same region as the patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10508521+1427914" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a patient with retinitis pigmentosa-12 (RP12; <a href="/entry/600105">600105</a>), <a href="#9" class="mim-tip-reference" title="den Hollander, A. I., ten Brink, J. B., de Kok, Y. J. M., van Soest, S., van den Born, L. I., van Driel, M. A., van de Pol, D. J. R., Payne, A. M., Bhattacharya, S. S., Kellner, U., Hoyng, C. B., Westerveld, A., Brunner, H. G., Bleeker-Wagemakers, E. M., Deutman, A. F., Heckenlively, J. R., Cremers, F. P. M., Bergen, A. A. B. <strong>Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12).</strong> Nature Genet. 23: 217-221, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10508521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10508521</a>] [<a href="https://doi.org/10.1038/13848" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10508521">den Hollander et al. (1999)</a> found a glu995-to-ter (E995X) mutation due to a 3118G-T transversion in the CRB1 gene and present in compound heterozygous state with an arg764-to-cys (R764C; <a href="#0004">604210.0004</a>) mutation on the other allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10508521" 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>.0004 RETINITIS PIGMENTOSA 12</strong>
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CRB1, ARG764CYS
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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> rs62635654 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs62635654;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/rs62635654?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=rs62635654" 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=rs62635654" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006086 OR RCV000086317 OR RCV000656137 OR RCV000787577 OR RCV001052374 OR RCV001074882 OR RCV001250604 OR RCV001352991 OR RCV002496279 OR RCV003447471 OR RCV003450615 OR RCV004540990" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006086, RCV000086317, RCV000656137, RCV000787577, RCV001052374, RCV001074882, RCV001250604, RCV001352991, RCV002496279, RCV003447471, RCV003450615, RCV004540990" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006086...</a>
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<p>For discussion of the arg764-to-cys (R764C) mutation in the CRB1 gene that was found in compound heterozygous state in a patient with retinitis pigmentosa-12 (RP12; <a href="/entry/600105">600105</a>) by <a href="#9" class="mim-tip-reference" title="den Hollander, A. I., ten Brink, J. B., de Kok, Y. J. M., van Soest, S., van den Born, L. I., van Driel, M. A., van de Pol, D. J. R., Payne, A. M., Bhattacharya, S. S., Kellner, U., Hoyng, C. B., Westerveld, A., Brunner, H. G., Bleeker-Wagemakers, E. M., Deutman, A. F., Heckenlively, J. R., Cremers, F. P. M., Bergen, A. A. B. <strong>Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12).</strong> Nature Genet. 23: 217-221, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10508521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10508521</a>] [<a href="https://doi.org/10.1038/13848" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10508521">den Hollander et al. (1999)</a>, see <a href="#0003">604210.0003</a>. The R764C mutation was also observed in compound heterozygous state with a ser430-to-ter (S430X) nonsense mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10508521" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0005" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0005 RETINITIS PIGMENTOSA 12</strong>
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CRB1, THR745MET
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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> rs28939720 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28939720;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/rs28939720?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=rs28939720" 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=rs28939720" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006087 OR RCV000086315 OR RCV000787576 OR RCV000809110 OR RCV001074789 OR RCV001196030 OR RCV001250601 OR RCV001257864 OR RCV001826422 OR RCV002496280" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006087, RCV000086315, RCV000787576, RCV000809110, RCV001074789, RCV001196030, RCV001250601, RCV001257864, RCV001826422, RCV002496280" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006087...</a>
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</span>
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</div>
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<span class="mim-text-font">
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<p>In a patient with retinitis pigmentosa-12 (RP12; <a href="/entry/600105">600105</a>), <a href="#9" class="mim-tip-reference" title="den Hollander, A. I., ten Brink, J. B., de Kok, Y. J. M., van Soest, S., van den Born, L. I., van Driel, M. A., van de Pol, D. J. R., Payne, A. M., Bhattacharya, S. S., Kellner, U., Hoyng, C. B., Westerveld, A., Brunner, H. G., Bleeker-Wagemakers, E. M., Deutman, A. F., Heckenlively, J. R., Cremers, F. P. M., Bergen, A. A. B. <strong>Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12).</strong> Nature Genet. 23: 217-221, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10508521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10508521</a>] [<a href="https://doi.org/10.1038/13848" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10508521">den Hollander et al. (1999)</a> observed homozygosity for a thr745-to-met (T745M) mutation due to a 2369C-T transition in the CRB1 gene. The same T745M mutation was present in compound heterozygous state with another missense mutation in 1 patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10508521" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0006 LEBER CONGENITAL AMAUROSIS 8</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<div style="float: left;">
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CRB1, ILE1100ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs62635659 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs62635659;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=rs62635659" 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=rs62635659" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006088 OR RCV000086340 OR RCV002490326" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006088, RCV000086340, RCV002490326" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006088...</a>
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</span>
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<div>
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<span class="mim-text-font">
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<p>In 2 brothers with Leber congenital amaurosis-8 (LCA8; <a href="/entry/613835">613835</a>), <a href="#7" class="mim-tip-reference" title="den Hollander, A. I., Heckenlively, J. R., van den Born, L. I., de Kok, Y. J. M., van der Velde-Visser, S. D., Kellner, U., Jurklies, B., van Schooneveld, M. J., Blankenagel, A., Rohrschneider, K., Wissinger, B., Cruysberg, J. R. M., Deutman, A. F., Brunner, H. G., Apfelstedt-Sylla, E., Hoyng, C. B., Cremers, F. P. M. <strong>Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the Crumbs homologue 1 (CRB1) gene.</strong> Am. J. Hum. Genet. 69: 198-203, 2001. Note: Erratum: Am. J. Hum. Genet. 69: 1160 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11389483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11389483</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11389483[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/321263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11389483">den Hollander et al. (2001)</a> found compound heterozygosity for a missense mutation (ile1100 to arg; I1100R) and a glu1333-to-ter mutation (E1333X; <a href="#0007">604210.0007</a>) in the CRB1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11389483" 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>
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<a id="0007" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0007 LEBER CONGENITAL AMAUROSIS 8</strong>
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</span>
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</h4>
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CRB1, GLU1333TER
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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> rs137853136 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853136;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/rs137853136?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=rs137853136" 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=rs137853136" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006089" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006089" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006089</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the glu1333-to-ter (E1333X) mutation in the CRB1 gene that was found in compound heterozygous state in brothers with Leber congenital amaurosis-8 (LCA8; <a href="/entry/613835">613835</a>) by <a href="#7" class="mim-tip-reference" title="den Hollander, A. I., Heckenlively, J. R., van den Born, L. I., de Kok, Y. J. M., van der Velde-Visser, S. D., Kellner, U., Jurklies, B., van Schooneveld, M. J., Blankenagel, A., Rohrschneider, K., Wissinger, B., Cruysberg, J. R. M., Deutman, A. F., Brunner, H. G., Apfelstedt-Sylla, E., Hoyng, C. B., Cremers, F. P. M. <strong>Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the Crumbs homologue 1 (CRB1) gene.</strong> Am. J. Hum. Genet. 69: 198-203, 2001. Note: Erratum: Am. J. Hum. Genet. 69: 1160 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11389483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11389483</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11389483[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/321263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11389483">den Hollander et al. (2001)</a>, see <a href="#0006">604210.0006</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11389483" 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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</span>
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</div>
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<div>
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<div>
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<a id="0008" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0008 RETINITIS PIGMENTOSA 12</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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<div style="float: left;">
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CRB1, LYS801TER
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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> rs137853137 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853137;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/rs137853137?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=rs137853137" 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=rs137853137" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006090 OR RCV000578757 OR RCV000691427 OR RCV000787578 OR RCV000787826 OR RCV001250606 OR RCV001275651 OR RCV002504753 OR RCV003450616 OR RCV004739293" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006090, RCV000578757, RCV000691427, RCV000787578, RCV000787826, RCV001250606, RCV001275651, RCV002504753, RCV003450616, RCV004739293" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006090...</a>
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</span>
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<div>
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<span class="mim-text-font">
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<p>In a brother and sister with retinitis pigmentosa (RP12; <a href="/entry/600105">600105</a>) who developed a Coats-like exudative vasculopathy (see <a href="/entry/300216">300216</a>), <a href="#7" class="mim-tip-reference" title="den Hollander, A. I., Heckenlively, J. R., van den Born, L. I., de Kok, Y. J. M., van der Velde-Visser, S. D., Kellner, U., Jurklies, B., van Schooneveld, M. J., Blankenagel, A., Rohrschneider, K., Wissinger, B., Cruysberg, J. R. M., Deutman, A. F., Brunner, H. G., Apfelstedt-Sylla, E., Hoyng, C. B., Cremers, F. P. M. <strong>Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the Crumbs homologue 1 (CRB1) gene.</strong> Am. J. Hum. Genet. 69: 198-203, 2001. Note: Erratum: Am. J. Hum. Genet. 69: 1160 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11389483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11389483</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11389483[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/321263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11389483">den Hollander et al. (2001)</a> found compound heterozygosity for a nonsense mutation, lys801 to ter (K801X), and a missense mutation, cys1181 to arg (C1181R; <a href="#0009">604210.0009</a>), in the CRB1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11389483" 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> rs62636291 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs62636291;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/rs62636291?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=rs62636291" 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=rs62636291" 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=RCV000006091 OR RCV000086346 OR RCV004814842" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006091, RCV000086346, RCV004814842" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006091...</a>
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<p>For discussion of the cys1181-to-arg (C1181R) mutation in the CRB1 gene that was found in compound heterozygous state in sibs with retinitis pigmentosa-12 (RP12; <a href="/entry/600105">600105</a>) by <a href="#7" class="mim-tip-reference" title="den Hollander, A. I., Heckenlively, J. R., van den Born, L. I., de Kok, Y. J. M., van der Velde-Visser, S. D., Kellner, U., Jurklies, B., van Schooneveld, M. J., Blankenagel, A., Rohrschneider, K., Wissinger, B., Cruysberg, J. R. M., Deutman, A. F., Brunner, H. G., Apfelstedt-Sylla, E., Hoyng, C. B., Cremers, F. P. M. <strong>Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the Crumbs homologue 1 (CRB1) gene.</strong> Am. J. Hum. Genet. 69: 198-203, 2001. Note: Erratum: Am. J. Hum. Genet. 69: 1160 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11389483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11389483</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11389483[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/321263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11389483">den Hollander et al. (2001)</a>, see <a href="#0008">604210.0008</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11389483" 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> rs137853138 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853138;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/rs137853138?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=rs137853138" 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=rs137853138" 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=RCV000006092 OR RCV000082821 OR RCV000262530 OR RCV000353078 OR RCV000723716 OR RCV001080229" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006092, RCV000082821, RCV000262530, RCV000353078, RCV000723716, RCV001080229" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006092...</a>
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<p>In all 6 affected members of a family with pigmented paravenous chorioretinal atrophy (PPCRA; <a href="/entry/172870">172870</a>), <a href="#18" class="mim-tip-reference" title="McKay, G. J., Clarke, S., Davis, J. A., Simpson, D. A. C., Silvestri, G. <strong>Pigmented paravenous chorioretinal atrophy is associated with a mutation within the crumbs homolog 1 (CRB1) gene.</strong> Invest. Ophthal. Vis. Sci. 46: 322-328, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15623792/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15623792</a>] [<a href="https://doi.org/10.1167/iovs.04-0734" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15623792">McKay et al. (2005)</a> identified heterozygosity for a val162-to-met (V162M) mutation within the fourth EGF-like domain of the CRB1 gene. PPCRA in this family was dominantly inherited but exhibited variable expressivity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15623792" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0011 LEBER CONGENITAL AMAUROSIS 8</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs62636275 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs62636275;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/rs62636275?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=rs62636275" 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=rs62636275" 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=RCV000006093 OR RCV000006094 OR RCV000086341 OR RCV000648818 OR RCV000786009 OR RCV001002998 OR RCV001073404 OR RCV003450617 OR RCV005007828" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006093, RCV000006094, RCV000086341, RCV000648818, RCV000786009, RCV001002998, RCV001073404, RCV003450617, RCV005007828" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006093...</a>
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<p>In all 4 affected members of a family of Middle Eastern origin segregating autosomal recessive Leber congenital amaurosis-8 (LCA8; <a href="/entry/613835">613835</a>) and high to extreme hyperopia, <a href="#1" class="mim-tip-reference" title="Abouzeid, H., Li, Y., Maumenee, I. H., Dharmaraj, S., Sundlin, O. <strong>A G1103R mutation in CRB1 is co-inherited with high hyperopia and Leber congenital amaurosis.</strong> Ophthalmic Genet. 27: 15-20, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16543197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16543197</a>] [<a href="https://doi.org/10.1080/13816810500481840" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16543197">Abouzeid et al. (2006)</a> identified homozygosity for a 3307G-A transition in exon 9 of the CRB1 gene, resulting in a gly1103-to-arg (G1103R) substitution at a highly conserved site in the protein. The mutation was found in heterozygous state in 4 unaffected family members and was not found in 104 healthy Caucasian volunteers. <a href="#1" class="mim-tip-reference" title="Abouzeid, H., Li, Y., Maumenee, I. H., Dharmaraj, S., Sundlin, O. <strong>A G1103R mutation in CRB1 is co-inherited with high hyperopia and Leber congenital amaurosis.</strong> Ophthalmic Genet. 27: 15-20, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16543197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16543197</a>] [<a href="https://doi.org/10.1080/13816810500481840" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16543197">Abouzeid et al. (2006)</a> showed that hyperopia and LCA were linked to the mutant CRB1 gene itself and were not dependent on unlinked modifiers. <a href="#1" class="mim-tip-reference" title="Abouzeid, H., Li, Y., Maumenee, I. H., Dharmaraj, S., Sundlin, O. <strong>A G1103R mutation in CRB1 is co-inherited with high hyperopia and Leber congenital amaurosis.</strong> Ophthalmic Genet. 27: 15-20, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16543197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16543197</a>] [<a href="https://doi.org/10.1080/13816810500481840" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16543197">Abouzeid et al. (2006)</a> noted that the G1103R mutation had previously been identified in compound heterozygous state in a patient with sporadic LCA by <a href="#13" class="mim-tip-reference" title="Hanein, S., Perrault, I., Gerber, S., Tanguy, G., Barbet, F., Ducroq, D., Calvas, P., Dollfus, H., Hamel, C., Lopponen, T., Munier, F., Santos, L., Shalev, S., Zafeiriou, D., Dufier, J.-L., Munnich, A., Rozet, J.-M., Kaplan, J. <strong>Leber congenital amaurosis: comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis.</strong> Hum. Mutat. 23: 306-317, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15024725/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15024725</a>] [<a href="https://doi.org/10.1002/humu.20010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15024725">Hanein et al. (2004)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15024725+16543197" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a consanguineous family with early-onset retinitis pigmentosa (RP12; <a href="/entry/600105">600105</a>), <a href="#3" class="mim-tip-reference" title="Benayoun, L., Spiegel, R., Auslender, N., Abbasi, A. H., Rizel, L., Hujeirat, Y., Salama, I., Garzozi, H. J., Allon-Shalev, S., Ben-Yosef, T. <strong>Genetic heterogeneity in two consanguineous families segregating early onset retinal degeneration: the pitfalls of homozygosity mapping.</strong> Am. J. Med. Genet. 149A: 650-656, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19140180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19140180</a>] [<a href="https://doi.org/10.1002/ajmg.a.32634" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19140180">Benayoun et al. (2009)</a> identified compound heterozygosity for the G1103R mutation and a 10-bp deletion (<a href="#0012">604210.0012</a>) in the CRB1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19140180" 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">rs281865175 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865175;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=rs281865175" 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=rs281865175" 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=RCV000006095 OR RCV000006096 OR RCV000086353 OR RCV001003001 OR RCV001851689" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006095, RCV000006096, RCV000086353, RCV001003001, RCV001851689" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006095...</a>
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<p>In 4 affected sibs from a consanguineous family with early-onset retinitis pigmentosa (RP12; <a href="/entry/600105">600105</a>), <a href="#3" class="mim-tip-reference" title="Benayoun, L., Spiegel, R., Auslender, N., Abbasi, A. H., Rizel, L., Hujeirat, Y., Salama, I., Garzozi, H. J., Allon-Shalev, S., Ben-Yosef, T. <strong>Genetic heterogeneity in two consanguineous families segregating early onset retinal degeneration: the pitfalls of homozygosity mapping.</strong> Am. J. Med. Genet. 149A: 650-656, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19140180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19140180</a>] [<a href="https://doi.org/10.1002/ajmg.a.32634" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19140180">Benayoun et al. (2009)</a> identified compound heterozygosity for the G1103R mutation (<a href="#0011">604210.0011</a>) in exon 9 and a 10-bp deletion (4121del10) in exon 12 of the CRB1 gene. Four unaffected sibs carried only 1 mutant allele; 1 carrier of the 10-bp deletion was found among 139 control samples screened, indicating a carrier rate of 0.72% in this population. <a href="#3" class="mim-tip-reference" title="Benayoun, L., Spiegel, R., Auslender, N., Abbasi, A. H., Rizel, L., Hujeirat, Y., Salama, I., Garzozi, H. J., Allon-Shalev, S., Ben-Yosef, T. <strong>Genetic heterogeneity in two consanguineous families segregating early onset retinal degeneration: the pitfalls of homozygosity mapping.</strong> Am. J. Med. Genet. 149A: 650-656, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19140180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19140180</a>] [<a href="https://doi.org/10.1002/ajmg.a.32634" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19140180">Benayoun et al. (2009)</a> noted that both mutations had previously been identified in homozygosity in families with Leber congenital amaurosis (LCA8; <a href="/entry/613835">613835</a>) (see <a href="#12" class="mim-tip-reference" title="Gerber, S., Perrault, I., Hanein, S., Shalev, S., Zlotogora, J., Barbet, F., Ducroq, D., Dufier, J.-L., Munnich, A., Rozet, J.-M., Kaplan, J. <strong>A novel mutation disrupting the cytoplasmic domain of CRB1 in a large consanguineous family of Palestinian origin affected with Leber congenital amaurosis.</strong> Ophthalmic Genet. 23: 225-235, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12567265/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12567265</a>] [<a href="https://doi.org/10.1076/opge.23.4.225.13879" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12567265">Gerber et al., 2002</a> and <a href="#0011">604210.0011</a>, respectively). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19140180+12567265" 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>.0013 LEBER CONGENITAL AMAUROSIS 8</strong>
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RETINITIS PIGMENTOSA 12, INCLUDED
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CRB1, CYS948TYR
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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> rs62645748 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs62645748;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/rs62645748?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=rs62645748" 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=rs62645748" 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=RCV000032814 OR RCV000032815 OR RCV000086331 OR RCV000505155 OR RCV000554663 OR RCV000762874 OR RCV000787579 OR RCV001097540 OR RCV001275657 OR RCV003313928 OR RCV003324500" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032814, RCV000032815, RCV000086331, RCV000505155, RCV000554663, RCV000762874, RCV000787579, RCV001097540, RCV001275657, RCV003313928, RCV003324500" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032814...</a>
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<p>In 7 patients with Leber congenital amaurosis (LCA8; <a href="/entry/613835">613835</a>), <a href="#17" class="mim-tip-reference" title="Lotery, A. J., Jacobson, S. G., Fishman, G. A., Weleber, R. G., Fulton, A. B., Namperumalsamy, P., Heon, E., Levin, A. V., Grover, S., Rosenow, J. R., Kopp, K. K., Sheffield, V. C., Stone, E. M. <strong>Mutations in the CRB1 gene cause Leber congenital amaurosis.</strong> Arch. Ophthal. 119: 415-420, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11231775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11231775</a>] [<a href="https://doi.org/10.1001/archopht.119.3.415" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11231775">Lotery et al. (2001)</a> identified a G-A transition in the CRB1 gene that resulted in a cys948-to-tyr (C948Y) substitution. The mutation was present in homozygosity in 1 patient, in compound heterozygosity with a missense and a frameshift mutation in 2 patients, respectively, and in heterozygosity in 4 patients. The mutation was not found in 280 control alleles. <a href="#17" class="mim-tip-reference" title="Lotery, A. J., Jacobson, S. G., Fishman, G. A., Weleber, R. G., Fulton, A. B., Namperumalsamy, P., Heon, E., Levin, A. V., Grover, S., Rosenow, J. R., Kopp, K. K., Sheffield, V. C., Stone, E. M. <strong>Mutations in the CRB1 gene cause Leber congenital amaurosis.</strong> Arch. Ophthal. 119: 415-420, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11231775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11231775</a>] [<a href="https://doi.org/10.1001/archopht.119.3.415" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11231775">Lotery et al. (2001)</a> noted that C948Y had previously been reported in patients with retinitis pigmentosa (RP12; <a href="/entry/600105">600105</a>) by <a href="#9" class="mim-tip-reference" title="den Hollander, A. I., ten Brink, J. B., de Kok, Y. J. M., van Soest, S., van den Born, L. I., van Driel, M. A., van de Pol, D. J. R., Payne, A. M., Bhattacharya, S. S., Kellner, U., Hoyng, C. B., Westerveld, A., Brunner, H. G., Bleeker-Wagemakers, E. M., Deutman, A. F., Heckenlively, J. R., Cremers, F. P. M., Bergen, A. A. B. <strong>Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12).</strong> Nature Genet. 23: 217-221, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10508521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10508521</a>] [<a href="https://doi.org/10.1038/13848" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10508521">den Hollander et al. (1999)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10508521+11231775" 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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Abouzeid, H., Li, Y., Maumenee, I. H., Dharmaraj, S., Sundlin, O.
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<strong>A G1103R mutation in CRB1 is co-inherited with high hyperopia and Leber congenital amaurosis.</strong>
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Ophthalmic Genet. 27: 15-20, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16543197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16543197</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16543197" 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/10.1080/13816810500481840" target="_blank">Full Text</a>]
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Bachmann, A., Schneider, M., Theilenberg, E., Grawe, F., Knust, E.
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<strong>Drosophila stardust is a partner of crumbs in the control of epithelial cell polarity.</strong>
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Nature 414: 638-643, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11740560/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11740560</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11740560" 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/10.1038/414638a" target="_blank">Full Text</a>]
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Benayoun, L., Spiegel, R., Auslender, N., Abbasi, A. H., Rizel, L., Hujeirat, Y., Salama, I., Garzozi, H. J., Allon-Shalev, S., Ben-Yosef, T.
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<strong>Genetic heterogeneity in two consanguineous families segregating early onset retinal degeneration: the pitfalls of homozygosity mapping.</strong>
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Am. J. Med. Genet. 149A: 650-656, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19140180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19140180</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19140180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.32634" target="_blank">Full Text</a>]
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Bleeker-Wagemakers, L. M., Gal, A., Kumar-Singh, R., van den Born, L. I., Li, Y., Schwinger, E., Sandkuijl, L. A., Bergen, A. A. B., Kenna, P., Humphries, P., Farrar, G. J.
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<strong>Evidence for nonallelic genetic heterogeneity in autosomal recessive retinitis pigmentosa.</strong>
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Genomics 14: 811-812, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1427914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1427914</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1427914" 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/s0888-7543(05)80195-8" target="_blank">Full Text</a>]
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Bujakowska, K., Audo, I., Mohand-Said, S., Lancelot, M.-E., Antonio, A., Germain, A., Leveillard, T., Letexier, M., Saraiva, J.-P., Lonjou, C., Carpentier, W., Sahel, J.-A., Bhattacharya, S. S., Zeitz, C.
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<strong>CRB1 mutations in inherited retinal dystrophies.</strong>
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Hum. Mutat. 33: 306-315, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22065545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22065545</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22065545[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22065545" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.21653" target="_blank">Full Text</a>]
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den Hollander, A. I., Davis, J., van der Velde-Visser, S. D., Zonneveld, M. N., Pierrottet, C. O., Koenekoop, R. K., Kellner, U., van den Born, L. I., Heckenlively, J. R., Hoyng, C. B., Handford, P. A., Roepman, R., Cremers, F. P. M.
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<strong>CRB1 mutation spectrum in inherited retinal dystrophies.</strong>
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Hum. Mutat. 24: 355-369, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15459956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15459956</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15459956" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.20093" target="_blank">Full Text</a>]
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<a id="den Hollander2001" class="mim-anchor"></a>
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den Hollander, A. I., Heckenlively, J. R., van den Born, L. I., de Kok, Y. J. M., van der Velde-Visser, S. D., Kellner, U., Jurklies, B., van Schooneveld, M. J., Blankenagel, A., Rohrschneider, K., Wissinger, B., Cruysberg, J. R. M., Deutman, A. F., Brunner, H. G., Apfelstedt-Sylla, E., Hoyng, C. B., Cremers, F. P. M.
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<strong>Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the Crumbs homologue 1 (CRB1) gene.</strong>
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Am. J. Hum. Genet. 69: 198-203, 2001. Note: Erratum: Am. J. Hum. Genet. 69: 1160 only, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11389483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11389483</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11389483[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11389483" 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/10.1086/321263" target="_blank">Full Text</a>]
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den Hollander, A. I., Johnson, K., de Kok, Y. J. M., Klebes, A., Brunner, H. G., Knust, E., Cremers, F. P. M.
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<strong>CRB1 has a cytoplasmic domain that is functionally conserved between human and Drosophila.</strong>
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Hum. Molec. Genet. 10: 2767-2773, 2001.
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[<a href="https://doi.org/10.1093/hmg/10.24.2767" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1006/geno.1999.5823" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.93.12.6025" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/humu.20010" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/ddg117" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1001/archopht.119.3.415" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1167/iovs.04-0734" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/ddg232" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/nature721" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1159/000472385" target="_blank">Full Text</a>]
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Marla J. F. O'Neill - updated : 2/8/2013
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Marla J. F. O'Neill - updated : 8/6/2012<br>Jane Kelly - updated : 3/6/2012<br>Marla J. F. O'Neill - updated : 10/18/2010<br>Anne M. Stumpf - updated : 2/9/2009<br>Jane Kelly - updated : 11/27/2007<br>Cassandra L. Kniffin - updated : 11/10/2005<br>George E. Tiller - updated : 9/12/2005<br>Jane Kelly - updated : 3/28/2005<br>George E. Tiller - updated : 12/20/2004<br>George E. Tiller - updated : 5/31/2002<br>Paul J. Converse - updated : 5/22/2002<br>Ada Hamosh - updated : 4/2/2002<br>Ada Hamosh - updated : 1/3/2002<br>Ada Hamosh - updated : 9/21/2001<br>Victor A. McKusick - updated : 8/16/2001
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Creation Date:
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<span class="mim-text-font">
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Victor A. McKusick : 9/30/1999
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carol : 09/13/2019
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carol : 11/28/2018<br>carol : 04/07/2015<br>mcolton : 4/6/2015<br>carol : 2/8/2013<br>alopez : 8/6/2012<br>terry : 8/6/2012<br>alopez : 3/6/2012<br>carol : 3/25/2011<br>carol : 10/18/2010<br>carol : 4/3/2009<br>alopez : 2/9/2009<br>carol : 10/21/2008<br>terry : 6/6/2008<br>carol : 11/27/2007<br>carol : 11/27/2007<br>carol : 11/13/2006<br>carol : 9/13/2006<br>carol : 9/8/2006<br>wwang : 11/17/2005<br>ckniffin : 11/10/2005<br>terry : 9/12/2005<br>carol : 4/1/2005<br>wwang : 3/28/2005<br>tkritzer : 12/20/2004<br>mgross : 5/14/2004<br>joanna : 3/17/2004<br>alopez : 11/25/2003<br>cwells : 6/12/2002<br>cwells : 5/31/2002<br>mgross : 5/22/2002<br>cwells : 4/5/2002<br>cwells : 4/4/2002<br>terry : 4/2/2002<br>alopez : 1/10/2002<br>terry : 1/3/2002<br>mcapotos : 12/21/2001<br>terry : 9/21/2001<br>cwells : 9/7/2001<br>cwells : 8/27/2001<br>terry : 8/16/2001<br>terry : 11/24/1999<br>alopez : 10/4/1999<br>alopez : 9/30/1999<br>alopez : 9/30/1999<br>alopez : 9/30/1999
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<strong>*</strong> 604210
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CRUMBS CELL POLARITY COMPLEX COMPONENT 1; CRB1
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<em>Alternative titles; symbols</em>
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CRUMBS, DROSOPHILA, HOMOLOG OF, 1
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<strong><em>HGNC Approved Gene Symbol: CRB1</em></strong>
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<strong>SNOMEDCT:</strong> 723450004;
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Cytogenetic location: 1q31.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 1:197,201,504-197,478,455 </span>
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</em>
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<span class="small">(from NCBI)</span>
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<strong>Gene-Phenotype Relationships</strong>
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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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1q31.3
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Leber congenital amaurosis 8
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613835
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Autosomal recessive
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3
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Pigmented paravenous chorioretinal atrophy
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172870
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Autosomal dominant
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3
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Retinitis pigmentosa-12
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600105
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Autosomal recessive
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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 isolate candidate genes for chorioretinal diseases, den Hollander et al. (1999) cloned cDNAs specifically or preferentially expressed in the human retina and the retinal pigment epithelium (RPE) through a novel suppression subtractive hybridization (SSH) method (Diatchenko et al., 1996). One of these cDNAs (RET3C11) mapped to 1q31-q32.1, a region harboring a gene involved in a severe form of autosomal recessive retinitis pigmentosa characterized by a typical preservation of the paraarteriolar RPE, designated RP12 (600105). Den Hollander et al. (1999) isolated the full-length cDNA, encoding an extracellular protein with 19 EGF-like domains, 3 laminin-A G-like domains, and a C-type lectin domain. This 1,376-amino acid protein, 35% identical to the protein 'crumbs' (CRB) of Drosophila melanogaster, was denoted CRB1 for crumbs homolog-1. The CRB1 gene consists of 11 exons and spans at least 40 kb. Northern blot analysis detected a 5-kb transcript in neural retina; RT-PCR detected expression additionally in adult and fetal brain. The similarity to Drosophila CRB suggested a role for CRB1 in cell-cell interaction and possibly in the maintenance of cell polarity in the retina. </p><p>Roh et al. (2002) obtained a full-length cDNA encoding CRB1. The protein contains a transmembrane segment and a 37-amino acid tail. It is associated in tight junctions with MPP5 (606958) and PATJ (603199). </p>
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<strong>Gene Function</strong>
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<p>The polarized architecture of epithelial cells depends on the highly stereotypic distribution of cellular junctions and other membrane-associated protein complexes. In epithelial cells of the Drosophila embryo, 3 distinct domains subdivide the lateral plasma membrane. The most apical one comprises the subapical complex. It is followed by the zonula adherens, and, further basally, by the septate junction. A core component of the subapical complex is the transmembrane protein crumbs, the cytoplasmic domain of which recruits the PDZ protein Patj (603199) into the complex. Cells lacking crumbs or the functionally related gene 'stardust' fail to organize a continuous zonular adherens and to maintain cell polarity. Bachmann et al. (2001) demonstrated that stardust provides an essential component of the subapical complex. Stardust proteins colocalize with crumbs and bind to the carboxy-terminal amino acids of its cytoplasmic tail. </p><p>Pellikka et al. (2002) showed that crumbs and CRB1 localize to corresponding subdomains of the photoreceptor apical plasma membrane: the stalk of the Drosophila photoreceptor and the inner segment of mammalian photoreceptors. The subdomains support the morphogenesis and orientation of the photosensitive membrane organelles: rhabdomeres and outer segments, respectively. Drosophila crumbs is required to maintain zonula adherens integrity during the rapid apical membrane expansion that builds the rhabdomere. Crumbs also regulates stalk development by stabilizing the membrane-associated spectrin cytoskeleton, a function mechanistically distinct from its role in epithelial apical-basal polarity. Pellikka et al. (2002) proposed that crumbs is a central component of a molecular scaffold that controls zonula adherens assembly and defines the stalk as an apical membrane subdomain. </p><p>Izaddoost et al. (2002) described the properties of crumbs that control the position and integrity of the photoreceptor adherens junction and photosensitive organ, or rhabdomere, in Drosophila. In contrast to normal photoreceptor adherens junctions and rhabdomeres, which span the depth of the retina, adherens junctions and rhabdomeres of crumbs-deficient photoreceptors initially accumulate at the top of the retina and fail to maintain their integrity as they stretch to the retinal floor. Izaddoost et al. (2002) showed that crumbs controls localization of the adherens junction through its intracellular domain containing a putative binding site for a protein 4.1 superfamily protein (FERM). Although loss of crumbs or overexpression of the FERM binding domain caused mislocalization of adherens junctions, they did not result in a significant loss of photoreceptor polarity. The intracellular domain of human CRB1 behaved similarly to its Drosophila counterpart when overexpressed in the fly eye. </p><p>A striking difference between CRB1 and crumbs is that the latter contains a transmembrane region and a 37-amino acid cytoplasmic domain. Den Hollander et al. (2001) described an alternative splice variant of human CRB1 that encodes a cytoplasmic domain 72% similar to that of Drosophila crumbs. Two intracellular subdomains that are necessary for function in Drosophila are absolutely conserved. Rescuing and overexpression studies in Drosophila showed that the cytoplasmic domains are functionally related between these distant species. The authors hypothesized that CRB1 may organize an intracellular protein scaffold in the human retina. </p><p>Jacobson et al. (2003) characterized the retinal organization in vivo of patients with CRB1 mutations and found that, unlike other inherited retinal degenerations, the CRB1 mutant retinas were remarkably thick in cross-section and lacked the distinct layers of normal adult retina. There were coarse outer and inner zones and a thick surface layer around the optic nerve. The abnormal retinal architecture in CRB1 mutations resembled that of immature normal retina. Jacobson et al. (2003) concluded that the CRB1 disease pathway disturbs the development of normal human retinal organization by interrupting naturally occurring apoptosis. </p>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<p>Den Hollander et al. (2004) stated that 71 different sequence variants had been identified in the CRB1 gene in patients with retinal dystrophies. They provided an overview of currently known CRB1 variants and discussed their effects. </p><p>Henderson et al. (2011) sought to identify CRB1 mutations in a large cohort of patients with recessive retinal dystrophies and to document the retinal phenotype and visual prognosis. They recruited 306 patients with Leber congenital amaurosis (LCA), early-onset childhood retinal dystrophy, or juvenile-onset retinitis pigmentosa to the study. Mutations in CRB1, including 17 novel mutations, were identified in 41 patients from 32 families, and those patients underwent detailed phenotyping. Common phenotypic features included hypermetropic refractive error, nummular pigmentation at the level of the retinal pigment epithelium (RPE), and increased retinal thickness on optical coherence tomography (OCT). Most patients had a clinical and electrophysiologic phenotype consistent with a diagnosis of LCA or rod-cone dystrophy, but 3 patients had electroretinogram evidence of cone-rod degeneration. A minority of patients developed peripheral retinal telangiectasia, which in some cases led to seclusio pupillae and angle-closure glaucoma. Henderson et al. (2011) concluded that mutations in CRB1 were associated with a range of recessively inherited retinal dystrophies, including LCA and childhood- and juvenile-onset rod-cone and cone-rod dystrophy. Although the phenotype was usually severe, in milder cases there was a window of opportunity for therapeutic intervention in early childhood. </p><p>Bujakowska et al. (2012) analyzed the CRB1 gene in 400 index patients with a provisional diagnosis of retinitis pigmentosa and identified 11 patients carrying likely pathogenic variants of CRB1. Analysis of the more than 150 previously reported CRB1 mutations and the clinical features of the respective patients showed that no specific allele combination could be assigned to a particular phenotype. Bujakowska et al. (2012) suggested that the modulation of phenotype in patients with CRB1 mutations is due to additional modifying factors, genetic and/or environmental. </p><p><strong><em>Retinitis Pigmentosa 12</em></strong></p><p>
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In 10 unrelated RP12 (600105) patients, den Hollander et al. (1999) identified a homozygous AluY insertion disrupting the open reading frame, 5 homozygous missense mutations, and 4 compound heterozygous mutations in the CRB1 gene. The distinct RPE abnormalities observed in RP12 patients suggested that CRB1 mutations trigger a novel mechanism of photoreceptor degeneration. </p><p>Den Hollander et al. (2001) identified CRB1 mutations in 5 of 9 patients who had RP with Coats-like exudative vasculopathy, a relatively rare complication of RP that may progress to partial or total retinal detachment. Given that 4 of 5 patients had developed the complication in one eye and that not all sibs with RP have the complication, den Hollander et al. (2001) suggested that CRB1 mutations should be considered an important risk factor for the Coats-like reaction, although its development may require additional genetic or environmental factors. </p><p>In affected members of a consanguineous family with early-onset retinitis pigmentosa, Benayoun et al. (2009) identified compound heterozygosity for a G1103R mutation (604210.0011) and a 10-bp deletion (604210.0012) in the CRB1 gene. Each mutation had previously been identified in homozygosity in a family diagnosed with Leber congenital amaurosis (LCA8; 613835). </p><p><strong><em>Leber Congenital Amaurosis 8</em></strong></p><p>
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Lotery et al. (2001) screened the candidate gene CRB1 in 190 patients with Leber congenital amaurosis (LCA8; 613835) who were negative for mutation in 6 known LCA genes and 140 controls, and identified 21 patients and 2 controls who harbored amino acid-altering sequence variants (p = 0.03; see, e.g., 604210.0013). The authors noted that the 21 CRB1 mutation-carrying patients represented 9% of their total cohort of 233 LCA patients, making CRB1 the most commonly mutated gene in this group of patients. </p><p>Because of the early onset of disease in patients who have retinal pigmentosa with preserved paraarteriolar retinal pigment epithelium (RP12), with severe loss of vision at ages of less than 20 years, den Hollander et al. (2001) considered CRB1 to be a good candidate gene for Leber congenital amaurosis. They detected mutations in CRB1 in 7 (13%) of 52 patients with LCA from the Netherlands, Germany, and the United States (see, e.g., 604210.0006-604210.0007). Although no clear-cut genotype-phenotype correlation could be established, den Hollander et al. (2001) found that patients with LCA, which is the most severe retinal dystrophy, carried null alleles more frequently than did patients with retinitis pigmentosa. </p><p>In all 4 affected members of a Middle Eastern family with LCA8 and high to extreme hyperopia, Abouzeid et al. (2006) found linkage of the disorder to 1q31 and identified homozygosity for a mutation in the CRB1 gene (G1103R; 604210.0011). Abouzeid et al. (2006) showed that hyperopia and LCA were linked to the mutant CRB1 gene itself and were not dependent on unlinked modifiers. </p><p><strong><em>Pigmented Paravenous Chorioretinal Atrophy</em></strong></p><p>
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In all 6 affected members of a family segregating pigmented paravenous chorioretinal atrophy (PPCRA; 172870), McKay et al. (2005) identified heterozygosity for a val162-to-met (V162M; 604210.0010) mutation. </p>
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<strong>Animal Model</strong>
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<p>Mehalow et al. (2003) identified a mouse model, retinal degeneration-8 (rd8), with a single base deletion in the Crb1 gene. The mutation was predicted to cause a frameshift and premature stop codon with loss of the transmembrane and cytoplasmic domains of CRB1. Similar to Drosophila crumbs (crb) mutants, staining for adherens junction proteins was discontinuous and fragmented. Shortened photoreceptor inner and outer segments were observed as early as 2 weeks after birth, suggesting a developmental defect in these structures rather than a degenerative process. Photoreceptor degeneration was observed only within regions of retinal spotting. Since photoreceptor dysplasia and degeneration in Crb1 mouse mutants strongly varied with genetic background, the authors suggested that the variable phenotypes of human patients with CRB1 mutations may be due to interactions with background modifiers in addition to allelic variations. </p>
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<strong>ALLELIC VARIANTS</strong>
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<strong>13 Selected Examples):</strong>
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<span class="mim-font">
|
|
<strong>.0001 RETINITIS PIGMENTOSA 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CRB1, ALU INS, NT2320
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000006083
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with retinitis pigmentosa with paraarteriolar preservation of retinal pigment epithelium (RP12; 600105), den Hollander et al. (1999) found a homozygous insertion of an Alu repeat DNA element in exon 7 at nucleotide 2320 of the CRB1 cDNA. The Alu element belonged to the AluY subfamily, was oriented in the antisense direction, contained a more than 70-nucleotide poly(A) tail, and was flanked by a 12-bp direct repeat consisting of CRB1 nucleotides 2309-2320. This insertion was present in heterozygous state in the unrelated parents and in 2 sibs of the patient, but not in 185 healthy controls. The Alu sequence showed a 5-prime truncation that was also observed in a pathologic Alu element inserted in the F9 gene of hemophilia B (Vidaud et al., 1993); see 300746.0098. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 RETINITIS PIGMENTOSA 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CRB1, MET1041THR
|
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|
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|
<br />
|
|
|
|
SNP: rs62635656,
|
|
|
|
|
|
gnomAD: rs62635656,
|
|
|
|
|
|
ClinVar: RCV000006084, RCV000086336, RCV001045972, RCV001075294, RCV001250615, RCV003450614, RCV004528086, RCV005007827
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with retinitis pigmentosa-12 (RP12; 600105), den Hollander et al. (1999) observed a homozygous nonconservative met1041-to-thr (M1041T) mutation in the CRB1 gene. This patient was from the family described by Bleeker-Wagemakers et al. (1992) in which the RP12 locus was originally mapped. The same mutation was found in heterozygosity in 1 of 100 healthy control individuals living in the same region as the patient. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 RETINITIS PIGMENTOSA 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CRB1, GLU995TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs62635655,
|
|
|
|
|
|
gnomAD: rs62635655,
|
|
|
|
|
|
ClinVar: RCV000006085, RCV000086334
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with retinitis pigmentosa-12 (RP12; 600105), den Hollander et al. (1999) found a glu995-to-ter (E995X) mutation due to a 3118G-T transversion in the CRB1 gene and present in compound heterozygous state with an arg764-to-cys (R764C; 604210.0004) mutation on the other allele. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 RETINITIS PIGMENTOSA 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CRB1, ARG764CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs62635654,
|
|
|
|
|
|
gnomAD: rs62635654,
|
|
|
|
|
|
ClinVar: RCV000006086, RCV000086317, RCV000656137, RCV000787577, RCV001052374, RCV001074882, RCV001250604, RCV001352991, RCV002496279, RCV003447471, RCV003450615, RCV004540990
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg764-to-cys (R764C) mutation in the CRB1 gene that was found in compound heterozygous state in a patient with retinitis pigmentosa-12 (RP12; 600105) by den Hollander et al. (1999), see 604210.0003. The R764C mutation was also observed in compound heterozygous state with a ser430-to-ter (S430X) nonsense mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 RETINITIS PIGMENTOSA 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CRB1, THR745MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28939720,
|
|
|
|
|
|
gnomAD: rs28939720,
|
|
|
|
|
|
ClinVar: RCV000006087, RCV000086315, RCV000787576, RCV000809110, RCV001074789, RCV001196030, RCV001250601, RCV001257864, RCV001826422, RCV002496280
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with retinitis pigmentosa-12 (RP12; 600105), den Hollander et al. (1999) observed homozygosity for a thr745-to-met (T745M) mutation due to a 2369C-T transition in the CRB1 gene. The same T745M mutation was present in compound heterozygous state with another missense mutation in 1 patient. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 LEBER CONGENITAL AMAUROSIS 8</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CRB1, ILE1100ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs62635659,
|
|
|
|
|
|
|
|
ClinVar: RCV000006088, RCV000086340, RCV002490326
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 brothers with Leber congenital amaurosis-8 (LCA8; 613835), den Hollander et al. (2001) found compound heterozygosity for a missense mutation (ile1100 to arg; I1100R) and a glu1333-to-ter mutation (E1333X; 604210.0007) in the CRB1 gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 LEBER CONGENITAL AMAUROSIS 8</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CRB1, GLU1333TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137853136,
|
|
|
|
|
|
gnomAD: rs137853136,
|
|
|
|
|
|
ClinVar: RCV000006089
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the glu1333-to-ter (E1333X) mutation in the CRB1 gene that was found in compound heterozygous state in brothers with Leber congenital amaurosis-8 (LCA8; 613835) by den Hollander et al. (2001), see 604210.0006. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 RETINITIS PIGMENTOSA 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CRB1, LYS801TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137853137,
|
|
|
|
|
|
gnomAD: rs137853137,
|
|
|
|
|
|
ClinVar: RCV000006090, RCV000578757, RCV000691427, RCV000787578, RCV000787826, RCV001250606, RCV001275651, RCV002504753, RCV003450616, RCV004739293
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a brother and sister with retinitis pigmentosa (RP12; 600105) who developed a Coats-like exudative vasculopathy (see 300216), den Hollander et al. (2001) found compound heterozygosity for a nonsense mutation, lys801 to ter (K801X), and a missense mutation, cys1181 to arg (C1181R; 604210.0009), in the CRB1 gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 RETINITIS PIGMENTOSA 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CRB1, CYS1181ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs62636291,
|
|
|
|
|
|
gnomAD: rs62636291,
|
|
|
|
|
|
ClinVar: RCV000006091, RCV000086346, RCV004814842
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the cys1181-to-arg (C1181R) mutation in the CRB1 gene that was found in compound heterozygous state in sibs with retinitis pigmentosa-12 (RP12; 600105) by den Hollander et al. (2001), see 604210.0008. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 PIGMENTED PARAVENOUS CHORIORETINAL ATROPHY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CRB1, VAL162MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137853138,
|
|
|
|
|
|
gnomAD: rs137853138,
|
|
|
|
|
|
ClinVar: RCV000006092, RCV000082821, RCV000262530, RCV000353078, RCV000723716, RCV001080229
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In all 6 affected members of a family with pigmented paravenous chorioretinal atrophy (PPCRA; 172870), McKay et al. (2005) identified heterozygosity for a val162-to-met (V162M) mutation within the fourth EGF-like domain of the CRB1 gene. PPCRA in this family was dominantly inherited but exhibited variable expressivity. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 LEBER CONGENITAL AMAUROSIS 8</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
RETINITIS PIGMENTOSA 12, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CRB1, GLY1103ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs62636275,
|
|
|
|
|
|
gnomAD: rs62636275,
|
|
|
|
|
|
ClinVar: RCV000006093, RCV000006094, RCV000086341, RCV000648818, RCV000786009, RCV001002998, RCV001073404, RCV003450617, RCV005007828
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In all 4 affected members of a family of Middle Eastern origin segregating autosomal recessive Leber congenital amaurosis-8 (LCA8; 613835) and high to extreme hyperopia, Abouzeid et al. (2006) identified homozygosity for a 3307G-A transition in exon 9 of the CRB1 gene, resulting in a gly1103-to-arg (G1103R) substitution at a highly conserved site in the protein. The mutation was found in heterozygous state in 4 unaffected family members and was not found in 104 healthy Caucasian volunteers. Abouzeid et al. (2006) showed that hyperopia and LCA were linked to the mutant CRB1 gene itself and were not dependent on unlinked modifiers. Abouzeid et al. (2006) noted that the G1103R mutation had previously been identified in compound heterozygous state in a patient with sporadic LCA by Hanein et al. (2004). </p><p>In affected members of a consanguineous family with early-onset retinitis pigmentosa (RP12; 600105), Benayoun et al. (2009) identified compound heterozygosity for the G1103R mutation and a 10-bp deletion (604210.0012) in the CRB1 gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 RETINITIS PIGMENTOSA 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
LEBER CONGENITAL AMAUROSIS 8, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CRB1, 10-BP DEL, NT4121
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs281865175,
|
|
|
|
|
|
|
|
ClinVar: RCV000006095, RCV000006096, RCV000086353, RCV001003001, RCV001851689
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 affected sibs from a consanguineous family with early-onset retinitis pigmentosa (RP12; 600105), Benayoun et al. (2009) identified compound heterozygosity for the G1103R mutation (604210.0011) in exon 9 and a 10-bp deletion (4121del10) in exon 12 of the CRB1 gene. Four unaffected sibs carried only 1 mutant allele; 1 carrier of the 10-bp deletion was found among 139 control samples screened, indicating a carrier rate of 0.72% in this population. Benayoun et al. (2009) noted that both mutations had previously been identified in homozygosity in families with Leber congenital amaurosis (LCA8; 613835) (see Gerber et al., 2002 and 604210.0011, respectively). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 LEBER CONGENITAL AMAUROSIS 8</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
RETINITIS PIGMENTOSA 12, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CRB1, CYS948TYR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs62645748,
|
|
|
|
|
|
gnomAD: rs62645748,
|
|
|
|
|
|
ClinVar: RCV000032814, RCV000032815, RCV000086331, RCV000505155, RCV000554663, RCV000762874, RCV000787579, RCV001097540, RCV001275657, RCV003313928, RCV003324500
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 7 patients with Leber congenital amaurosis (LCA8; 613835), Lotery et al. (2001) identified a G-A transition in the CRB1 gene that resulted in a cys948-to-tyr (C948Y) substitution. The mutation was present in homozygosity in 1 patient, in compound heterozygosity with a missense and a frameshift mutation in 2 patients, respectively, and in heterozygosity in 4 patients. The mutation was not found in 280 control alleles. Lotery et al. (2001) noted that C948Y had previously been reported in patients with retinitis pigmentosa (RP12; 600105) by den Hollander et al. (1999). </p>
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<div>
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<h4>
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<span class="mim-font">
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den Hollander, A. I., Davis, J., van der Velde-Visser, S. D., Zonneveld, M. N., Pierrottet, C. O., Koenekoop, R. K., Kellner, U., van den Born, L. I., Heckenlively, J. R., Hoyng, C. B., Handford, P. A., Roepman, R., Cremers, F. P. M.
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den Hollander, A. I., Heckenlively, J. R., van den Born, L. I., de Kok, Y. J. M., van der Velde-Visser, S. D., Kellner, U., Jurklies, B., van Schooneveld, M. J., Blankenagel, A., Rohrschneider, K., Wissinger, B., Cruysberg, J. R. M., Deutman, A. F., Brunner, H. G., Apfelstedt-Sylla, E., Hoyng, C. B., Cremers, F. P. M.
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<strong>Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the Crumbs homologue 1 (CRB1) gene.</strong>
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den Hollander, A. I., ten Brink, J. B., de Kok, Y. J. M., van Soest, S., van den Born, L. I., van Driel, M. A., van de Pol, D. J. R., Payne, A. M., Bhattacharya, S. S., Kellner, U., Hoyng, C. B., Westerveld, A., Brunner, H. G., Bleeker-Wagemakers, E. M., Deutman, A. F., Heckenlively, J. R., Cremers, F. P. M., Bergen, A. A. B.
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<strong>Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12).</strong>
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den Hollander, A. I., van Driel, M. A., de Kok, Y. J. M., van de Pol, D. J. R., Hoyng, C. B., Brunner, H. G., Deutman, A. F., Cremers, F. P. M.
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<strong>Pigmented paravenous chorioretinal atrophy is associated with a mutation within the crumbs homolog 1 (CRB1) gene.</strong>
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Mehalow, A. K., Kameya, S., Smith, R. S., Hawes, N. L., Denegre, J. M., Young, J. A., Bechtold, L., Haider, N. B., Tepass, U., Heckenlively, J. R., Chang, B., Naggert, J. K., Nishina, P. M.
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Pellikka, M., Tanentzapf, G., Pinto, M., Smith, C., McGlade, C. J., Ready, D. F., Tepass, U.
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<strong>Crumbs, the Drosophila homologue of human CRB1/RP12, is essential for photoreceptor morphogenesis.</strong>
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Roh, M. H., Makarova, O., Liu, C.-J., Shin, K., Lee, S., Laurinec, S., Goyal, M., Wiggins, R., Margolis, B.
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<li>
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<p class="mim-text-font">
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Vidaud, D., Vidaud, M., Bahnak, B. R., Siguret, V., Sanchez, S. G., Laurian, Y., Meyer, D., Goossens, M., Lavergne, J. M.
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<strong>Haemophilia B due to a de novo insertion of a human-specific Alu subfamily member within the coding region of the factor IX gene.</strong>
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</ol>
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<span class="text-nowrap mim-text-font">
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Contributors:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 2/8/2013<br>Marla J. F. O'Neill - updated : 8/6/2012<br>Jane Kelly - updated : 3/6/2012<br>Marla J. F. O'Neill - updated : 10/18/2010<br>Anne M. Stumpf - updated : 2/9/2009<br>Jane Kelly - updated : 11/27/2007<br>Cassandra L. Kniffin - updated : 11/10/2005<br>George E. Tiller - updated : 9/12/2005<br>Jane Kelly - updated : 3/28/2005<br>George E. Tiller - updated : 12/20/2004<br>George E. Tiller - updated : 5/31/2002<br>Paul J. Converse - updated : 5/22/2002<br>Ada Hamosh - updated : 4/2/2002<br>Ada Hamosh - updated : 1/3/2002<br>Ada Hamosh - updated : 9/21/2001<br>Victor A. McKusick - updated : 8/16/2001
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Creation Date:
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<span class="mim-text-font">
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Victor A. McKusick : 9/30/1999
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carol : 09/13/2019<br>carol : 11/28/2018<br>carol : 04/07/2015<br>mcolton : 4/6/2015<br>carol : 2/8/2013<br>alopez : 8/6/2012<br>terry : 8/6/2012<br>alopez : 3/6/2012<br>carol : 3/25/2011<br>carol : 10/18/2010<br>carol : 4/3/2009<br>alopez : 2/9/2009<br>carol : 10/21/2008<br>terry : 6/6/2008<br>carol : 11/27/2007<br>carol : 11/27/2007<br>carol : 11/13/2006<br>carol : 9/13/2006<br>carol : 9/8/2006<br>wwang : 11/17/2005<br>ckniffin : 11/10/2005<br>terry : 9/12/2005<br>carol : 4/1/2005<br>wwang : 3/28/2005<br>tkritzer : 12/20/2004<br>mgross : 5/14/2004<br>joanna : 3/17/2004<br>alopez : 11/25/2003<br>cwells : 6/12/2002<br>cwells : 5/31/2002<br>mgross : 5/22/2002<br>cwells : 4/5/2002<br>cwells : 4/4/2002<br>terry : 4/2/2002<br>alopez : 1/10/2002<br>terry : 1/3/2002<br>mcapotos : 12/21/2001<br>terry : 9/21/2001<br>cwells : 9/7/2001<br>cwells : 8/27/2001<br>terry : 8/16/2001<br>terry : 11/24/1999<br>alopez : 10/4/1999<br>alopez : 9/30/1999<br>alopez : 9/30/1999<br>alopez : 9/30/1999
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