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<title>
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Entry
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- *605755 - DOUBLECORTIN DOMAIN-CONTAINING PROTEIN 2; DCDC2
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- OMIM
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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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Advanced Search
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<a href="/search/advanced/entry"> OMIM </a>
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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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<a href="/search/advanced/geneMap"> Gene Map </a>
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<p />
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<div class="row">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*605755</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 role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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</li>
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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/605755">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=ENSG00000146038;t=ENST00000378454" 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=51473" 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=605755" 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=ENSG00000146038;t=ENST00000378454" 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_001195610,NM_016356" 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_016356" 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=605755" 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=09308&isoform_id=09308_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/DCDC2" 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/6453454,6684527,6684530,20521782,29791794,117938307,147744557,307219252" 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/Q9UHG0" 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=51473" 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=ENSG00000146038;t=ENST00000378454" 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=DCDC2" 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=DCDC2" 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+51473" 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/DCDC2" 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:51473" 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/51473" 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=chr6&hgg_gene=ENST00000378454.8&hgg_start=24171755&hgg_end=24383292&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">
|
|
<span class="panel-title">
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<span class="small">
|
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
|
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:18141" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=605755[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=605755[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/DCDC2/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/ENSG00000146038" 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=DCDC2" 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=DCDC2" 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=DCDC2" 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="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=DCDC2&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/PA134978716" 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:18141" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:2652818" 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/DCDC2#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:2652818" 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/51473/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=51473" 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="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
|
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00007374;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00007374 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00012328;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00012328 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00012332;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00012332 </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 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">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
|
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=DCDC2&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
|
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
|
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<div class="text-right">
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</div>
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<div>
|
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
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605755
|
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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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DOUBLECORTIN DOMAIN-CONTAINING PROTEIN 2; DCDC2
|
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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>
|
|
<span class="mim-font">
|
|
RU2<br />
|
|
RU2S
|
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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>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=DCDC2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">DCDC2</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/6/110?start=-3&limit=10&highlight=110">6p22.3</a>
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr6:24171755-24383292&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'})">6:24,171,755-24,383,292</a> </span>
|
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</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
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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>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
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<tr class="active">
|
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<th>
|
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Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
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|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=610212,616217,617394" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
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<th>
|
|
Inheritance
|
|
</th>
|
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<th>
|
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Phenotype <br /> mapping key
|
|
</th>
|
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</tr>
|
|
</thead>
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<p>The DCDC2 gene encodes a protein containing 2 doublecortin peptide domains similar to those in the doublecortin gene (DCX; <a href="/entry/300121">300121</a>) (<a href="#6" class="mim-tip-reference" title="Meng, H., Smith, S. D., Hager, K., Held, M., Liu, J., Olson, R. K., Pennington, B. F., DeFries, J. C., Gelernter, J., O'Reilly-Pol, T., Somlo, S., Skudlarski, P., Shaywitz, S. E., Shaywitz, B. A., Marchione, K., Wang, Y., Paramasivam, M., LoTurco, J. J., Page, G. P., Gruen, J. R. <strong>DCDC2 is associated with reading disability and modulates neuronal development in the brain.</strong> Proc. Nat. Acad. Sci. 102: 17053-17058, 2005. Note: Erratum: Proc. Nat. Acad. Sci. 102: 18763 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16278297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16278297</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16278297[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0508591102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16278297">Meng et al., 2005</a>). DCDC2 plays a role in the inhibition of canonical WNT (<a href="/entry/164820">164820</a>) signaling (<a href="#7" class="mim-tip-reference" title="Schueler, M., Braun, D. A., Chandrasekar, G., Gee, H. Y., Klasson, T. D., Halbritter, J., Bieder, A., Porath, J. D., Airik, R., Zhou, W., LoTurco, J. J., Che, A., and 17 others. <strong>DCDC2 mutations cause a renal-hepatic ciliopathy by disrupting Wnt signaling.</strong> Am. J. Hum. Genet. 96: 81-92, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25557784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25557784</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25557784[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2014.12.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25557784">Schueler et al., 2015</a>). DCDC2 is a ciliary protein that binds tubulin and enhances microtubule polymerization (summary by <a href="#1" class="mim-tip-reference" title="Girard, M., Bizet, A. A., Lachaux, A., Gonzales, E., Filhol, E.,Collardeau-Frachon, S., Jeanpierre, C., Henry, C., Fabre, M., Viremouneix, L., Galmiche, L., Debray, D., and 10 others. <strong>DCDC2 mutations cause neonatal sclerosing cholangitis.</strong> Hum. Mutat. 37: 1025-1029, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27319779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27319779</a>] [<a href="https://doi.org/10.1002/humu.23031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27319779">Girard et al., 2016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16278297+25557784+27319779" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By screening cells expressing both HLA-B7 and kidney tumor cell RNA with autologous cytolytic T cells, followed by PCR, <a href="#11" class="mim-tip-reference" title="van den Eynde, B. J., Gaugler, B., Probst-Kepper, M., Michaux, L., Devuyst, O., Lorge, F., Weynants, P., Boon, T. <strong>A new antigen recognized by cytolytic T lymphocytes on a human kidney tumor results from reverse strand transcription.</strong> J. Exp. Med. 190: 1793-1799, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10601354/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10601354</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10601354[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/10.1084/jem.190.12.1793" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10601354">van den Eynde et al. (1999)</a> obtained cDNAs encoding RU2, which is identical to the KIAA1154 gene identified by <a href="#4" class="mim-tip-reference" title="Hirosawa, M., Nagase, T., Ishikawa, K., Kikuno, R., Nomura, N., Ohara, O. <strong>Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain.</strong> DNA Res. 6: 329-336, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10574461/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10574461</a>] [<a href="https://doi.org/10.1093/dnares/6.5.329" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10574461">Hirosawa et al. (1999)</a>. Genomic sequence analysis determined that RU2 is transcribed as a 'normal' gene, resulting in a sense transcript (RU2S), and in the opposite direction, resulting in a shorter antisense transcript (RU2AS; <a href="/entry/608211">608211</a>) found in tumors. Testing of synthetic peptides determined that the tumor antigen binding to HLA-B7 has the sequence LPRWPPPQL. Northern blot analysis revealed that the full-length gene is expressed as a 2.2-kb transcript. RT-PCR analysis detected ubiquitous expression of the full-length RU2S transcript, but expression of the RU2AS transcript was restricted to normal kidney, bladder, liver, and testis, as well as tumors of various histologic origins. The deduced RU2S protein contains 476 amino acids, while the RU2AS protein contains 84 residues. <a href="#11" class="mim-tip-reference" title="van den Eynde, B. J., Gaugler, B., Probst-Kepper, M., Michaux, L., Devuyst, O., Lorge, F., Weynants, P., Boon, T. <strong>A new antigen recognized by cytolytic T lymphocytes on a human kidney tumor results from reverse strand transcription.</strong> J. Exp. Med. 190: 1793-1799, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10601354/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10601354</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10601354[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/10.1084/jem.190.12.1793" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10601354">Van den Eynde et al. (1999)</a> concluded that potentially useful antigens for cancer immunotherapy cannot be predicted from the sequence of the normal cellular protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10574461+10601354" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using RT-PCR and Northern blot analysis, <a href="#8" class="mim-tip-reference" title="Schumacher, J., Anthoni, H., Dahdouh, F., Konig, I. R., Hillmer, A. M., Kluck, N., Manthey, M., Plume, E., Warnke, A., Remschmidt, H., Hulsmann, J., Cichon, S., Lindgren, C. M., Propping, P., Zucchelli, M., Ziegler, A., Peyrard-Janvid, M., Schulte-Korne, G., Nothen, M. M., Kere, J. <strong>Strong genetic evidence of DCDC2 as a susceptibility gene for dyslexia.</strong> Am. J. Hum. Genet. 78: 52-62, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16385449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16385449</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16385449[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/10.1086/498992" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16385449">Schumacher et al. (2006)</a> demonstrated that DCDC2 is expressed in the adult and fetal central nervous system (CNS). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16385449" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using quantitative real-time RT-PCR of human brain, <a href="#6" class="mim-tip-reference" title="Meng, H., Smith, S. D., Hager, K., Held, M., Liu, J., Olson, R. K., Pennington, B. F., DeFries, J. C., Gelernter, J., O'Reilly-Pol, T., Somlo, S., Skudlarski, P., Shaywitz, S. E., Shaywitz, B. A., Marchione, K., Wang, Y., Paramasivam, M., LoTurco, J. J., Page, G. P., Gruen, J. R. <strong>DCDC2 is associated with reading disability and modulates neuronal development in the brain.</strong> Proc. Nat. Acad. Sci. 102: 17053-17058, 2005. Note: Erratum: Proc. Nat. Acad. Sci. 102: 18763 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16278297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16278297</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16278297[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0508591102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16278297">Meng et al. (2005)</a> showed that DCDC2 exhibited highest expression in entorhinal cortex, inferior temporal cortex, medial temporal cortex, hypothalamus, amygdala, and hippocampus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16278297" 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="Schueler, M., Braun, D. A., Chandrasekar, G., Gee, H. Y., Klasson, T. D., Halbritter, J., Bieder, A., Porath, J. D., Airik, R., Zhou, W., LoTurco, J. J., Che, A., and 17 others. <strong>DCDC2 mutations cause a renal-hepatic ciliopathy by disrupting Wnt signaling.</strong> Am. J. Hum. Genet. 96: 81-92, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25557784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25557784</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25557784[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2014.12.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25557784">Schueler et al. (2015)</a> found that DCDC2 colocalized with acetylated alpha-tubulin (see TUBA1A, <a href="/entry/602529">602529</a>) at the axoneme of primary cilia of human renal tubule cells and cholangiocytes in liver, and to multiciliated ependymal cells and pia mater cells in mouse brain. However, DCDC2 did not localize to the basal body. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25557784" 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 postnatal rat and mouse inner ear, <a href="#3" class="mim-tip-reference" title="Grati, M., Chakchouk, I., Ma, Q., Bensaid, M., Desmidt, A., Turki, N., Yan, D., Baanannou, A., Mittal, R., Driss, N., Blanton, S., Farooq, A., Lu, Z., Liu, X. Z., Masmoudi, S. <strong>A missense mutation in DCDC2 causes human recessive deafness DFNB66, likely by interfering with sensory hair cell and supporting cell cilia length regulation.</strong> Hum. Molec. Genet. 24: 2482-2491, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25601850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25601850</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25601850[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddv009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25601850">Grati et al. (2015)</a> found that Dcdc2 localized to the kinocilia of inner, outer, and vestibular hair cells and to the primary cilia of all supporting cell types. It localized along the entire length, with increasing concentrations toward the tip. Dcdc2 was found in association with the cellular microtubule network. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25601850" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Girard, M., Bizet, A. A., Lachaux, A., Gonzales, E., Filhol, E.,Collardeau-Frachon, S., Jeanpierre, C., Henry, C., Fabre, M., Viremouneix, L., Galmiche, L., Debray, D., and 10 others. <strong>DCDC2 mutations cause neonatal sclerosing cholangitis.</strong> Hum. Mutat. 37: 1025-1029, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27319779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27319779</a>] [<a href="https://doi.org/10.1002/humu.23031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27319779">Girard et al. (2016)</a> found expression of DCDC2 in the cytoplasm and in cilia of cholangiocytes in liver bile ducts. <a href="#2" class="mim-tip-reference" title="Grammatikopoulos, T., Sambrotta, M., Strautnieks, S., Foskett, P., Knisely, A. S., Wagner, B., Deheragoda, M., Starling, C., Mieli-Vergani, G., Smith, J., University of Washington Center for Mendelian Genomics, Bull, L., Thompson, R. J. <strong>Mutations in DCDC2 (doublecortin domain containing protein 2) in neonatal sclerosing cholangitis.</strong> J. Hepatol. 65: 1179-1187, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27469900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27469900</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27469900[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.jhep.2016.07.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27469900">Grammatikopoulos et al. (2016)</a> found expression of the DCDC2 gene in cuboidal cholangiocytes in smaller intrahepatic bile ducts, with only faint focal marking in columnar cholangiocytes of larger and extrahepatic bile ducts. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=27469900+27319779" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>DCDC2 Intron 2 Short Tandem Repeat BV677278</em></strong></p><p>
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Within intron 2 of the DCDC2 gene, <a href="#6" class="mim-tip-reference" title="Meng, H., Smith, S. D., Hager, K., Held, M., Liu, J., Olson, R. K., Pennington, B. F., DeFries, J. C., Gelernter, J., O'Reilly-Pol, T., Somlo, S., Skudlarski, P., Shaywitz, S. E., Shaywitz, B. A., Marchione, K., Wang, Y., Paramasivam, M., LoTurco, J. J., Page, G. P., Gruen, J. R. <strong>DCDC2 is associated with reading disability and modulates neuronal development in the brain.</strong> Proc. Nat. Acad. Sci. 102: 17053-17058, 2005. Note: Erratum: Proc. Nat. Acad. Sci. 102: 18763 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16278297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16278297</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16278297[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0508591102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16278297">Meng et al. (2005)</a> identified a 168-bp purine-rich region containing a polymorphic compound short tandem repeat (STR) composed of 10 alleles containing variable copy numbers of (GAGAGGAAGGAAA)n and (GGAA)n repeat units. Database analysis identified 131 putative transcription factor binding sites distributed throughout the purine-rich region, including multiple copies of binding sites for the brain-related transcription factors PEAS3 (ETV4; <a href="/entry/600711">600711</a>) and NFATP (NFATC2; <a href="/entry/600490">600490</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16278297" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using electrophoretic mobility shift assays, <a href="#5" class="mim-tip-reference" title="Meng, H., Powers, N. R., Tang, L., Cope, N. A., Zhang, P.-X., Fuleihan, R., Gibson, C., Page, G. P., Gruen, J. R. <strong>A dyslexia-associated variant in DCDC2 changes gene expression.</strong> Behav. Genet. 41: 58-66, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21042874/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21042874</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21042874[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/10.1007/s10519-010-9408-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21042874">Meng et al. (2011)</a> showed that the conserved polymorphic purine-rich STR in intron 2 of the DCDC2 gene, which they called BV677278, bound nuclear proteins in a human brain lysate as well as in lymphoma cells. Expression of the 6 most common alleles of BV677278 in P19 cells, multipotent murine cells that can differentiate into neurons and neuroglia, showed that the alleles have a range of DCDC2-specific enhancer activities. The findings suggested that BV677278 alleles can modify DCDC2 expression to various degrees, which may link to changes in neural migration in the central nervous system. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21042874" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using FISH, <a href="#11" class="mim-tip-reference" title="van den Eynde, B. J., Gaugler, B., Probst-Kepper, M., Michaux, L., Devuyst, O., Lorge, F., Weynants, P., Boon, T. <strong>A new antigen recognized by cytolytic T lymphocytes on a human kidney tumor results from reverse strand transcription.</strong> J. Exp. Med. 190: 1793-1799, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10601354/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10601354</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10601354[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/10.1084/jem.190.12.1793" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10601354">van den Eynde et al. (1999)</a> mapped the DCDC2 gene to chromosome 6p22.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10601354" 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 cellular studies, <a href="#7" class="mim-tip-reference" title="Schueler, M., Braun, D. A., Chandrasekar, G., Gee, H. Y., Klasson, T. D., Halbritter, J., Bieder, A., Porath, J. D., Airik, R., Zhou, W., LoTurco, J. J., Che, A., and 17 others. <strong>DCDC2 mutations cause a renal-hepatic ciliopathy by disrupting Wnt signaling.</strong> Am. J. Hum. Genet. 96: 81-92, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25557784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25557784</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25557784[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2014.12.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25557784">Schueler et al. (2015)</a> found that DCDC2 fully or partially colocalized with acetylated alpha-tubulin to the spindle microtubules during metaphase and anaphase; to the abscission structure during late telophase/diakinesis; and to the ciliary axoneme in ciliated cells during interphase. Throughout those cell-cycle phases, DCDC2 was excluded from the basal body (in interphase), the mitotic spindle poles (in metaphase and anaphase), and the midbody (in diakinesis). Coimmunoprecipitation studies showed that DCDC2 interacted with DVL1 (<a href="/entry/601365">601365</a>), DVL2 (<a href="/entry/602151">602151</a>), and DVL3 (<a href="/entry/601368">601368</a>). DCDC2 also interacted with JIP1 (MAPK8IP1; <a href="/entry/604641">604641</a>), which mediates MAPK signaling. Knockdown of DCDC2 increased beta-catenin (CTNNB1; <a href="/entry/116806">116806</a>)-induced activation of T cell factor (TCF)-dependent transcription, and overexpression of DCDC2 reduced TCF-dependent transcription. These findings suggested that DCDC2 normally inhibits WNT signaling, and that loss of DCDC2 results in constitutive activation of the WNT signaling pathway. Knockdown of DCDC2 in a kidney cell culture system resulted in significantly fewer cilia compared to control, but the kidney cells formed normal spheroids without severe changes in lumen formation. Treatment of the DCDC2-null cells with a Wnt inhibitor restored the cilia defects. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25557784" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Nephronophthisis 19</em></strong></p><p>
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In 2 unrelated patients with nephronophthisis-19 (NPHP19; <a href="/entry/616217">616217</a>) with early-onset severe hepatic fibrosis, <a href="#7" class="mim-tip-reference" title="Schueler, M., Braun, D. A., Chandrasekar, G., Gee, H. Y., Klasson, T. D., Halbritter, J., Bieder, A., Porath, J. D., Airik, R., Zhou, W., LoTurco, J. J., Che, A., and 17 others. <strong>DCDC2 mutations cause a renal-hepatic ciliopathy by disrupting Wnt signaling.</strong> Am. J. Hum. Genet. 96: 81-92, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25557784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25557784</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25557784[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2014.12.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25557784">Schueler et al. (2015)</a> identified homozygous or compound heterozygous truncating mutations in the DCDC2 gene (<a href="#0001">605755.0001</a>-<a href="#0003">605755.0003</a>). The mutation in the first patient was found by a combination of homozygosity mapping and whole-exome sequencing of 100 families with a similar disorder. The mutations in the subsequent patient were found by sequencing the DCDC2 gene in 800 families with a similar disorder. All mutations abrogated the normal inhibition of CTNNB1-induced activation of TCF-dependent transcription, resulting in increased WNT signaling. Cellular studies as well as studies in zebrafish showed that inhibition of the Wnt signaling pathway could rescue some of the defects associated with loss of dcdc2, suggesting a role for this pathway in the pathogenesis of NPHP19. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25557784" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 13-year-old African Caribbean girl from Saint Vincent and the Grenadines with NPHP19, <a href="#9" class="mim-tip-reference" title="Slater, B., Bekheirnia, N., Angelo, J., Bi, W., Braun, M. C., Bekheirnia, M. R. <strong>Nephronophthisis due to a novel DCDC2 variant in a patient from African-Caribbean descent: a case report.</strong> Am. J. Med. Genet. 182A: 527-531, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31821705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31821705</a>] [<a href="https://doi.org/10.1002/ajmg.a.61440" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31821705">Slater et al. (2020)</a> identified a homozygous nonsense mutation in the DCDC2 gene (S128X; <a href="#0009">605755.0009</a>). The DCDC2 gene was located in a 2.1-Mb area of homozygosity. In total, the patient was found to have 53 Mb of homozygosity, indicating identity by descent originating from a common ancestor between her parents. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31821705" 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>Autosomal Recessive Deafness 66</em></strong></p><p>
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In affected members of a consanguineous Tunisian family with autosomal recessive deafness-66 (DFNB66; <a href="/entry/610212">610212</a>), <a href="#3" class="mim-tip-reference" title="Grati, M., Chakchouk, I., Ma, Q., Bensaid, M., Desmidt, A., Turki, N., Yan, D., Baanannou, A., Mittal, R., Driss, N., Blanton, S., Farooq, A., Lu, Z., Liu, X. Z., Masmoudi, S. <strong>A missense mutation in DCDC2 causes human recessive deafness DFNB66, likely by interfering with sensory hair cell and supporting cell cilia length regulation.</strong> Hum. Molec. Genet. 24: 2482-2491, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25601850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25601850</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25601850[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddv009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25601850">Grati et al. (2015)</a> identified a homozygous missense mutation in the DCDC2 gene (Q424P; <a href="#0004">605755.0004</a>). The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family. Expression of mutant DCDC2a in hair cells and supporting cells caused cilium structural defects, and knockdown of the gene in zebrafish impaired hair cell survival and function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25601850" 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>Neonatal Sclerosing Cholangitis</em></strong></p><p>
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In 4 patients from 2 unrelated consanguineous families with neonatal sclerosing cholangitis (NSC; <a href="/entry/617394">617394</a>), <a href="#1" class="mim-tip-reference" title="Girard, M., Bizet, A. A., Lachaux, A., Gonzales, E., Filhol, E.,Collardeau-Frachon, S., Jeanpierre, C., Henry, C., Fabre, M., Viremouneix, L., Galmiche, L., Debray, D., and 10 others. <strong>DCDC2 mutations cause neonatal sclerosing cholangitis.</strong> Hum. Mutat. 37: 1025-1029, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27319779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27319779</a>] [<a href="https://doi.org/10.1002/humu.23031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27319779">Girard et al. (2016)</a> identified 2 different homozygous mutations in the DCDC2 gene (<a href="#0005">605755.0005</a> and <a href="#0006">605755.0006</a>). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Patient cells showed loss of DCDC2 immunostaining in the ciliary axoneme of liver cholangiocytes and fewer cilia on cholangiocytes, as well as abnormal accumulation of the mutant protein in the cytoplasm compared to controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27319779" 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 7 patients from 6 unrelated families, many of Greek origin, with NSC, <a href="#2" class="mim-tip-reference" title="Grammatikopoulos, T., Sambrotta, M., Strautnieks, S., Foskett, P., Knisely, A. S., Wagner, B., Deheragoda, M., Starling, C., Mieli-Vergani, G., Smith, J., University of Washington Center for Mendelian Genomics, Bull, L., Thompson, R. J. <strong>Mutations in DCDC2 (doublecortin domain containing protein 2) in neonatal sclerosing cholangitis.</strong> J. Hepatol. 65: 1179-1187, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27469900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27469900</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27469900[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.jhep.2016.07.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27469900">Grammatikopoulos et al. (2016)</a> identified homozygous or compound heterozygous truncating mutations in the DCDC2 gene (see, e.g., <a href="#0001">605755.0001</a>; <a href="#0002">605755.0002</a>; <a href="#0007">605755.0007</a>; <a href="#0008">605755.0008</a>). The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. Parental DNA was only available for 1 patient, but the results confirmed segregation of the mutations with the disorder within the family. Patient liver samples showed absence of DCDC2 expression, consistent with a complete loss of function, as well as absence of normally constituted primary cilia in cholangiocytes. The patients were part of a cohort of 12 families with the disorder who underwent whole-exome sequencing; direct sequencing of the DCDC2 gene in 10 patients from 8 additional families did not identify any mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27469900" 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>Associations Pending Confirmation</em></strong></p><p>
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For a discussion of a possible association between variation in the DCDC2 gene and dyslexia, see DYX2 (<a href="/entry/600202">600202</a>).</p>
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Sci. 102: 18763 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16278297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16278297</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16278297[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0508591102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16278297">Meng et al. (2005)</a> demonstrated that Dcdc2 RNA interference introduced into cells at the cerebral ventricular zone of rat embryos resulted in altered neuronal migration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16278297" 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="Schueler, M., Braun, D. A., Chandrasekar, G., Gee, H. Y., Klasson, T. D., Halbritter, J., Bieder, A., Porath, J. D., Airik, R., Zhou, W., LoTurco, J. J., Che, A., and 17 others. <strong>DCDC2 mutations cause a renal-hepatic ciliopathy by disrupting Wnt signaling.</strong> Am. J. Hum. Genet. 96: 81-92, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25557784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25557784</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25557784[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2014.12.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25557784">Schueler et al. (2015)</a> found that Dcdc2-null mice developed periportal hepatic fibrosis with biliary duct proliferation at age 11 months. Knockdown of the dcdc2 gene in zebrafish embryos resulted in typical ciliopathy-related morphologic defects, including ventrally curved body axis, hydrocephalus, kidney cysts, kinky tails, and occasional pericardial edema. Laterality defects were also observed. Treatment with iCRT14, an inhibitor of the Wnt signaling pathway, rescued some of the defects, but high concentrations were toxic to embryos. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25557784" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Grati, M., Chakchouk, I., Ma, Q., Bensaid, M., Desmidt, A., Turki, N., Yan, D., Baanannou, A., Mittal, R., Driss, N., Blanton, S., Farooq, A., Lu, Z., Liu, X. Z., Masmoudi, S. <strong>A missense mutation in DCDC2 causes human recessive deafness DFNB66, likely by interfering with sensory hair cell and supporting cell cilia length regulation.</strong> Hum. Molec. Genet. 24: 2482-2491, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25601850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25601850</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25601850[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddv009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25601850">Grati et al. (2015)</a> found that morpholino knockdown of dcdc2b in zebrafish resulted in high levels of hair cell abnormalities, such as body deformations, and often in the internalization of the stereocilia hair bundles and their respective kinocilia, reflecting early steps of hair cell degeneration. There was a reduction in the number of saccular hair cells as well as a reduction of hair cell response to stimuli. Morpholino morphants were not capable of swimming or hearing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25601850" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=605755[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000157642 OR RCV000477678" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000157642, RCV000477678" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000157642...</a>
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In a patient, born of consanguineous parents, with nephronophthisis-19 (NPHP19; <a href="/entry/616217">616217</a>), <a href="#7" class="mim-tip-reference" title="Schueler, M., Braun, D. A., Chandrasekar, G., Gee, H. Y., Klasson, T. D., Halbritter, J., Bieder, A., Porath, J. D., Airik, R., Zhou, W., LoTurco, J. J., Che, A., and 17 others. <strong>DCDC2 mutations cause a renal-hepatic ciliopathy by disrupting Wnt signaling.</strong> Am. J. Hum. Genet. 96: 81-92, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25557784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25557784</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25557784[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2014.12.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25557784">Schueler et al. (2015)</a> identified a homozygous c.649A-T transversion (c.649A-T, NM_001195610.1) in exon 6 of the DCDC2 gene, resulting in a lys217-to-ter (K217X) substitution within the second doublecortin domain. The mutation was found by homozygosity mapping and whole-exome sequencing. In vitro cellular immunohistochemical studies showed that mutant DCDC2 failed to localize properly to primary cilia. The mutant protein was unable to rescue ciliopathy-related morphologic defects in dcdc2-null zebrafish, consistent with a loss of function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25557784" 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>Sclerosing Cholangitis, Neonatal</em></strong></p><p>
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In a girl (patient 1), born of consanguineous parents of Asian descent, with neonatal sclerosing cholangitis (NSC; <a href="/entry/617394">617394</a>), <a href="#2" class="mim-tip-reference" title="Grammatikopoulos, T., Sambrotta, M., Strautnieks, S., Foskett, P., Knisely, A. S., Wagner, B., Deheragoda, M., Starling, C., Mieli-Vergani, G., Smith, J., University of Washington Center for Mendelian Genomics, Bull, L., Thompson, R. J. <strong>Mutations in DCDC2 (doublecortin domain containing protein 2) in neonatal sclerosing cholangitis.</strong> J. Hepatol. 65: 1179-1187, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27469900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27469900</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27469900[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.jhep.2016.07.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27469900">Grammatikopoulos et al. (2016)</a> identified homozygosity for the K217X mutation in the DCDC2 gene. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was filtered against the 1000 Genomes Project and Exome Sequencing Project databases. Parental DNA was not available for segregation analysis. Patient liver samples showed absence of DCDC2 expression, consistent with a complete loss of function, as well as absence of normally constituted primary cilia in cholangiocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27469900" 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> rs757704417 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs757704417;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/rs757704417?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=rs757704417" 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=rs757704417" 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=RCV000157643 OR RCV000477717 OR RCV001335811 OR RCV002498782 OR RCV002515058" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000157643, RCV000477717, RCV001335811, RCV002498782, RCV002515058" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000157643...</a>
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In a Czech patient with nephronophthisis-19 (NPHP19; <a href="/entry/616217">616217</a>), <a href="#7" class="mim-tip-reference" title="Schueler, M., Braun, D. A., Chandrasekar, G., Gee, H. Y., Klasson, T. D., Halbritter, J., Bieder, A., Porath, J. D., Airik, R., Zhou, W., LoTurco, J. J., Che, A., and 17 others. <strong>DCDC2 mutations cause a renal-hepatic ciliopathy by disrupting Wnt signaling.</strong> Am. J. Hum. Genet. 96: 81-92, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25557784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25557784</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25557784[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2014.12.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25557784">Schueler et al. (2015)</a> identified compound heterozygous mutations in the DCDC2 gene: a 2-bp deletion (c.123_124delGT, NM_001195610.1) in exon 2, resulting in a frameshift and premature termination (Ser42GlnfsTer72) within the first doublecortin domain, and an A-to-G transition in intron 3 (c.349-2A-G; <a href="#0003">605755.0003</a>), resulting in a splicing defect, a frameshift, and premature termination (Val117LeufsTer54). The patient was ascertained from a larger cohort of 800 families with NPHP-related ciliopathies who underwent direct sequencing of the DCDC2 gene. In vitro cellular immunohistochemical studies showed that mutant DCDC2 failed to localize properly to primary cilia. Expression of the deletion mutation was unable to rescue ciliopathy-related morphologic defects in dcdc2-null zebrafish, consistent with a loss of function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25557784" 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>Sclerosing Cholangitis, Neonatal</em></strong></p><p>
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In an 18-year-old Caucasian man (patient 6), born of unrelated parents, with neonatal sclerosing cholangitis (NSC; <a href="/entry/617394">617394</a>), <a href="#2" class="mim-tip-reference" title="Grammatikopoulos, T., Sambrotta, M., Strautnieks, S., Foskett, P., Knisely, A. S., Wagner, B., Deheragoda, M., Starling, C., Mieli-Vergani, G., Smith, J., University of Washington Center for Mendelian Genomics, Bull, L., Thompson, R. J. <strong>Mutations in DCDC2 (doublecortin domain containing protein 2) in neonatal sclerosing cholangitis.</strong> J. Hepatol. 65: 1179-1187, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27469900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27469900</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27469900[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.jhep.2016.07.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27469900">Grammatikopoulos et al. (2016)</a> identified homozygosity for the c.123_124delGT mutation in the DCDC2 gene. Another patient (patient 5) with NSC2 was compound heterozygous for the c.123_124delGT mutation and a nonsense mutation (L297X; <a href="#0007">605755.0007</a>). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, were filtered against the 1000 Genomes Project and Exome Sequencing Project databases. Parental DNA for patient 6 was not available for segregation analysis, but the unaffected parents of patient 5 were each heterozygous for 1 of the mutations. Patient liver samples showed absence of DCDC2 expression, consistent with a complete loss of function, as well as absence of normally constituted primary cilia in cholangiocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27469900" 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> rs760040426 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs760040426;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/rs760040426?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=rs760040426" 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=rs760040426" 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=RCV000157644 OR RCV000731261 OR RCV001850190 OR RCV002498783" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000157644, RCV000731261, RCV001850190, RCV002498783" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000157644...</a>
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<p>For discussion of the c.349-2A-G mutation (c.349-2A-G, NM_001195610.1) in the DCDC2 gene that was found in compound heterozygous state in a patient with nephronophthisis-19 (NPHP19; <a href="/entry/616217">616217</a>) by <a href="#7" class="mim-tip-reference" title="Schueler, M., Braun, D. A., Chandrasekar, G., Gee, H. Y., Klasson, T. D., Halbritter, J., Bieder, A., Porath, J. D., Airik, R., Zhou, W., LoTurco, J. J., Che, A., and 17 others. <strong>DCDC2 mutations cause a renal-hepatic ciliopathy by disrupting Wnt signaling.</strong> Am. J. Hum. Genet. 96: 81-92, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25557784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25557784</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25557784[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2014.12.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25557784">Schueler et al. (2015)</a>, see <a href="#0002">605755.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25557784" 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 DEAFNESS, AUTOSOMAL RECESSIVE 66 (1 family)</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">rs794729665 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs794729665;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=rs794729665" 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=rs794729665" 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=RCV000157618 OR RCV000185587" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000157618, RCV000185587" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000157618...</a>
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<p>In affected members of a consanguineous Tunisian family with autosomal recessive deafness-66 (DFNB66; <a href="/entry/610212">610212</a>), originally reported by <a href="#10" class="mim-tip-reference" title="Tlili, A., Mannikko, M., Charfedine, I., Lahmar, I., Benzina, Z., Ben Amor, M., Driss, N., Ala-Kokko, L., Drira, M., Masmoudi, S., Ayadi, H. <strong>A novel autosomal recessive non-syndromic deafness locus, DFNB66, maps to chromosome 6p21.2-22.3 in a large Tunisian consanguineous family.</strong> Hum. Hered. 60: 123-128, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16244493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16244493</a>] [<a href="https://doi.org/10.1159/000088974" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16244493">Tlili et al. (2005)</a>, <a href="#3" class="mim-tip-reference" title="Grati, M., Chakchouk, I., Ma, Q., Bensaid, M., Desmidt, A., Turki, N., Yan, D., Baanannou, A., Mittal, R., Driss, N., Blanton, S., Farooq, A., Lu, Z., Liu, X. Z., Masmoudi, S. <strong>A missense mutation in DCDC2 causes human recessive deafness DFNB66, likely by interfering with sensory hair cell and supporting cell cilia length regulation.</strong> Hum. Molec. Genet. 24: 2482-2491, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25601850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25601850</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25601850[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddv009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25601850">Grati et al. (2015)</a> identified a homozygous c.1271A-C transversion (c.1271A-C, NM_001195610) in the DCDC2 gene, resulting in a gln424-to-pro (Q424P) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family and was not found in the dbSNP (build 37), 1000 Genomes Project, or Exome Sequencing Project databases, or in 435 ancestry-matched controls. Overexpression of both wildtype and mutant DCDC2 in COS-7 cells disrupted the intracellular microtubule network by inducing the formation of extended cytosolic microtubule cables. In rat hair cells, Q424P caused a 2- to 3-fold increase in cilia length compared to wildtype, as well as other ciliary abnormalities, such as branching, duplication, and triplication, and stereocilia bundle degeneration. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25601850+16244493" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 SCLEROSING CHOLANGITIS, NEONATAL</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">rs1042640142 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1042640142;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=rs1042640142" 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=rs1042640142" 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=RCV000477748" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000477748" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000477748</a>
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<p>In 2 brothers, born of consanguineous parents, with neonatal sclerosing cholangitis (NSC; <a href="/entry/617394">617394</a>), <a href="#1" class="mim-tip-reference" title="Girard, M., Bizet, A. A., Lachaux, A., Gonzales, E., Filhol, E.,Collardeau-Frachon, S., Jeanpierre, C., Henry, C., Fabre, M., Viremouneix, L., Galmiche, L., Debray, D., and 10 others. <strong>DCDC2 mutations cause neonatal sclerosing cholangitis.</strong> Hum. Mutat. 37: 1025-1029, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27319779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27319779</a>] [<a href="https://doi.org/10.1002/humu.23031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27319779">Girard et al. (2016)</a> identified a homozygous c.51G-C transversion (c.51G-C, NM_016356.3) in exon 1 of the DCDC2 gene, resulting in a lys17-to-asn (K17N) substitution at a highly conserved residue at the beginning of the first doublecortin domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the dbSNP, 1000 Genomes Project, Exome Variant Server, or ExAC databases, or in an in-house database of 7,477 exomes. Patient cells showed loss of DCDC2 immunostaining in the ciliary axoneme of liver cholangiocytes and fewer cilia on cholangiocytes, as well as abnormal accumulation of the mutant protein in the cytoplasm compared to controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27319779" 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>.0006 SCLEROSING CHOLANGITIS, NEONATAL</strong>
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DCDC2, 132-BP DEL, NT426
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000477686" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000477686" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000477686</a>
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<p>In 2 sibs, born of consanguineous parents, with neonatal sclerosing cholangitis (NSC; <a href="/entry/617394">617394</a>), <a href="#1" class="mim-tip-reference" title="Girard, M., Bizet, A. A., Lachaux, A., Gonzales, E., Filhol, E.,Collardeau-Frachon, S., Jeanpierre, C., Henry, C., Fabre, M., Viremouneix, L., Galmiche, L., Debray, D., and 10 others. <strong>DCDC2 mutations cause neonatal sclerosing cholangitis.</strong> Hum. Mutat. 37: 1025-1029, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27319779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27319779</a>] [<a href="https://doi.org/10.1002/humu.23031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27319779">Girard et al. (2016)</a> identified a homozygous 132-bp deletion (c.426_557del, NM_016356.3) in the DCDC2 gene, resulting in an in-frame deletion of 14 residues (Phe142_Arg186del) encompassing the entire exon 4 within the second doublecortin domain. The mutation, which was found by ciliary gene-targeting sequencing, segregated with the disorder in the family. It was not found in the dbSNP, 1000 Genomes Project, Exome Variant Server, or ExAC databases, or in an in-house database of 7,477 exomes. PCR analysis of patient cells confirmed the deletion. Patient cells showed loss of DCDC2 immunostaining in the ciliary axoneme of liver cholangiocytes and fewer cilia on cholangiocytes, as well as abnormal accumulation of the mutant protein in the cytoplasm compared to controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27319779" 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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DCDC2, LEU297TER
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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> rs1050411259 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1050411259;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/rs1050411259?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=rs1050411259" 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=rs1050411259" 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=RCV000477711 OR RCV002475927 OR RCV002525737" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000477711, RCV002475927, RCV002525737" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000477711...</a>
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<p>In a 12-year-old girl of Greek descent (patient 2) neonatal sclerosing cholangitis (NSC; <a href="/entry/617394">617394</a>), <a href="#2" class="mim-tip-reference" title="Grammatikopoulos, T., Sambrotta, M., Strautnieks, S., Foskett, P., Knisely, A. S., Wagner, B., Deheragoda, M., Starling, C., Mieli-Vergani, G., Smith, J., University of Washington Center for Mendelian Genomics, Bull, L., Thompson, R. J. <strong>Mutations in DCDC2 (doublecortin domain containing protein 2) in neonatal sclerosing cholangitis.</strong> J. Hepatol. 65: 1179-1187, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27469900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27469900</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27469900[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.jhep.2016.07.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27469900">Grammatikopoulos et al. (2016)</a> identified a homozygous c.890T-A transversion (c.890T-A, NM_001195610) in exon 7 of the DCDC2 gene, resulting in a leu297-to-ter (L297X) substitution. Three additional patients from 2 families were compound heterozygous for L297X and another pathogenic DCDC2 mutation: 1 Greek patient (patient 5) carried a 2-bp deletion (c.123_124delGT; <a href="#0002">605755.0002</a>) on the other allele, whereas 2 Greek sibs (patients 4 and 7) carried a 1-bp duplication in exon 4 (c.529dupA; <a href="#0008">605755.0008</a>), resulting in a frameshift and premature termination (Ile177AsnfsTer20), on the other allele. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, were filtered against the 1000 Genomes Project and Exome Sequencing Project databases. Parental DNA was not available for segregation analysis for the sibs, but each unaffected parent of patient 5 was heterozygous for 1 of the mutations. Patient liver samples showed absence of DCDC2 expression, consistent with a complete loss of function, as well as absence of normally constituted primary cilia in cholangiocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27469900" 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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DCDC2, 1-BP DUP, 529A
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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> rs904944428 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs904944428;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/rs904944428?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=rs904944428" 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=rs904944428" 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=RCV000477740 OR RCV000593742 OR RCV000692639 OR RCV005034007" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000477740, RCV000593742, RCV000692639, RCV005034007" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000477740...</a>
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<p>For discussion of the 1-bp duplication (c.529dupA, NM_001195610) in exon 4 of the DCDC2 gene, resulting in a frameshift and premature termination (Ile177AsnfsTer20), that was found in compound heterozygous state in 2 sibs with neonatal sclerosing cholangitis (NSC; <a href="/entry/617394">617394</a>) by <a href="#2" class="mim-tip-reference" title="Grammatikopoulos, T., Sambrotta, M., Strautnieks, S., Foskett, P., Knisely, A. S., Wagner, B., Deheragoda, M., Starling, C., Mieli-Vergani, G., Smith, J., University of Washington Center for Mendelian Genomics, Bull, L., Thompson, R. J. <strong>Mutations in DCDC2 (doublecortin domain containing protein 2) in neonatal sclerosing cholangitis.</strong> J. Hepatol. 65: 1179-1187, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27469900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27469900</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27469900[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.jhep.2016.07.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27469900">Grammatikopoulos et al. (2016)</a>, see <a href="#0007">605755.0007</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27469900" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 NEPHRONOPHTHISIS 19</strong>
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DCDC2, SER128TER (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs904520404;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs904520404</a>)
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs904520404 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs904520404;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/rs904520404?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=rs904520404" 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=rs904520404" 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=RCV000595112 OR RCV001722542 OR RCV002491217" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000595112, RCV001722542, RCV002491217" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000595112...</a>
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<p>In a 13-year-old African Caribbean girl from Saint Vincent and the Grenadines with nephronophthisis-19 (NPHP19; <a href="/entry/616217">616217</a>), <a href="#9" class="mim-tip-reference" title="Slater, B., Bekheirnia, N., Angelo, J., Bi, W., Braun, M. C., Bekheirnia, M. R. <strong>Nephronophthisis due to a novel DCDC2 variant in a patient from African-Caribbean descent: a case report.</strong> Am. J. Med. Genet. 182A: 527-531, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31821705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31821705</a>] [<a href="https://doi.org/10.1002/ajmg.a.61440" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31821705">Slater et al. (2020)</a> identified homozygosity for a c.383C-G transversion in exon 3 the DCDC2 gene, resulting in a ser128-to-ter (S128X) substitution. The mutation was identified by whole-exome sequencing. The DCDC2 gene was located in a 2.1-Mb area of homozygosity. In total, the patient was found to have 53 Mb of homozygosity, indicating identity by descent originating from a common ancestor between her parents. Functional studies were not performed. The patient also had psychiatric features, and the authors noted that the patient had variants of unknown significance in 5 other genes that were possibly related to the clinical phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31821705" 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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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-font">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
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<a id="Girard2016" class="mim-anchor"></a>
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Girard, M., Bizet, A. A., Lachaux, A., Gonzales, E., Filhol, E.,Collardeau-Frachon, S., Jeanpierre, C., Henry, C., Fabre, M., Viremouneix, L., Galmiche, L., Debray, D., and 10 others.
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<strong>DCDC2 mutations cause neonatal sclerosing cholangitis.</strong>
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Hum. Mutat. 37: 1025-1029, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27319779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27319779</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27319779" 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.23031" target="_blank">Full Text</a>]
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<a id="Grammatikopoulos2016" class="mim-anchor"></a>
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Grammatikopoulos, T., Sambrotta, M., Strautnieks, S., Foskett, P., Knisely, A. S., Wagner, B., Deheragoda, M., Starling, C., Mieli-Vergani, G., Smith, J., University of Washington Center for Mendelian Genomics, Bull, L., Thompson, R. J.
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<strong>Mutations in DCDC2 (doublecortin domain containing protein 2) in neonatal sclerosing cholangitis.</strong>
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J. Hepatol. 65: 1179-1187, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27469900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27469900</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27469900[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=27469900" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.jhep.2016.07.017" target="_blank">Full Text</a>]
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<a id="Grati2015" class="mim-anchor"></a>
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Grati, M., Chakchouk, I., Ma, Q., Bensaid, M., Desmidt, A., Turki, N., Yan, D., Baanannou, A., Mittal, R., Driss, N., Blanton, S., Farooq, A., Lu, Z., Liu, X. Z., Masmoudi, S.
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<strong>A missense mutation in DCDC2 causes human recessive deafness DFNB66, likely by interfering with sensory hair cell and supporting cell cilia length regulation.</strong>
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Hum. Molec. Genet. 24: 2482-2491, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25601850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25601850</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25601850[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=25601850" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddv009" target="_blank">Full Text</a>]
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<a id="Hirosawa1999" class="mim-anchor"></a>
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Hirosawa, M., Nagase, T., Ishikawa, K., Kikuno, R., Nomura, N., Ohara, O.
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<strong>Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain.</strong>
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DNA Res. 6: 329-336, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10574461/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10574461</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10574461" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/dnares/6.5.329" target="_blank">Full Text</a>]
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<a id="Meng2011" class="mim-anchor"></a>
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Meng, H., Powers, N. R., Tang, L., Cope, N. A., Zhang, P.-X., Fuleihan, R., Gibson, C., Page, G. P., Gruen, J. R.
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<strong>A dyslexia-associated variant in DCDC2 changes gene expression.</strong>
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Behav. Genet. 41: 58-66, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21042874/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21042874</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21042874[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=21042874" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s10519-010-9408-3" target="_blank">Full Text</a>]
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<a id="Meng2005" class="mim-anchor"></a>
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Meng, H., Smith, S. D., Hager, K., Held, M., Liu, J., Olson, R. K., Pennington, B. F., DeFries, J. C., Gelernter, J., O'Reilly-Pol, T., Somlo, S., Skudlarski, P., Shaywitz, S. E., Shaywitz, B. A., Marchione, K., Wang, Y., Paramasivam, M., LoTurco, J. J., Page, G. P., Gruen, J. R.
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<strong>DCDC2 is associated with reading disability and modulates neuronal development in the brain.</strong>
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Proc. Nat. Acad. Sci. 102: 17053-17058, 2005. Note: Erratum: Proc. Nat. Acad. Sci. 102: 18763 only, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16278297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16278297</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16278297[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=16278297" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0508591102" target="_blank">Full Text</a>]
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<a id="Schueler2015" class="mim-anchor"></a>
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Schueler, M., Braun, D. A., Chandrasekar, G., Gee, H. Y., Klasson, T. D., Halbritter, J., Bieder, A., Porath, J. D., Airik, R., Zhou, W., LoTurco, J. J., Che, A., and 17 others.
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<strong>DCDC2 mutations cause a renal-hepatic ciliopathy by disrupting Wnt signaling.</strong>
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Am. J. Hum. Genet. 96: 81-92, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25557784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25557784</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25557784[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=25557784" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2014.12.002" target="_blank">Full Text</a>]
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<a id="Schumacher2006" class="mim-anchor"></a>
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Schumacher, J., Anthoni, H., Dahdouh, F., Konig, I. R., Hillmer, A. M., Kluck, N., Manthey, M., Plume, E., Warnke, A., Remschmidt, H., Hulsmann, J., Cichon, S., Lindgren, C. M., Propping, P., Zucchelli, M., Ziegler, A., Peyrard-Janvid, M., Schulte-Korne, G., Nothen, M. M., Kere, J.
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<strong>Strong genetic evidence of DCDC2 as a susceptibility gene for dyslexia.</strong>
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Am. J. Hum. Genet. 78: 52-62, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16385449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16385449</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16385449[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=16385449" 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/10.1086/498992" target="_blank">Full Text</a>]
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</p>
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<a id="9" class="mim-anchor"></a>
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<a id="Slater2020" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Slater, B., Bekheirnia, N., Angelo, J., Bi, W., Braun, M. C., Bekheirnia, M. R.
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<strong>Nephronophthisis due to a novel DCDC2 variant in a patient from African-Caribbean descent: a case report.</strong>
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Am. J. Med. Genet. 182A: 527-531, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31821705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31821705</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31821705" 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.61440" target="_blank">Full Text</a>]
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</p>
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<a id="10" class="mim-anchor"></a>
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<a id="Tlili2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tlili, A., Mannikko, M., Charfedine, I., Lahmar, I., Benzina, Z., Ben Amor, M., Driss, N., Ala-Kokko, L., Drira, M., Masmoudi, S., Ayadi, H.
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<strong>A novel autosomal recessive non-syndromic deafness locus, DFNB66, maps to chromosome 6p21.2-22.3 in a large Tunisian consanguineous family.</strong>
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Hum. Hered. 60: 123-128, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16244493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16244493</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16244493" 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/10.1159/000088974" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="van den Eynde1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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van den Eynde, B. J., Gaugler, B., Probst-Kepper, M., Michaux, L., Devuyst, O., Lorge, F., Weynants, P., Boon, T.
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<strong>A new antigen recognized by cytolytic T lymphocytes on a human kidney tumor results from reverse strand transcription.</strong>
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J. Exp. Med. 190: 1793-1799, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10601354/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10601354</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10601354[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=10601354" 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/10.1084/jem.190.12.1793" target="_blank">Full Text</a>]
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</p>
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</ol>
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<a id="contributors" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 09/23/2021
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 03/23/2017<br>Cassandra L. Kniffin - updated : 6/29/2015<br>Cassandra L. Kniffin - updated : 2/9/2015<br>Matthew B. Gross - updated : 7/17/2013<br>Victor A. McKusick - updated : 12/29/2005<br>Cassandra L. Kniffin - updated : 11/17/2005
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Paul J. Converse : 3/22/2001
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</span>
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</div>
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<a id="editHistory" class="mim-anchor"></a>
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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joanna : 04/13/2022
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</span>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 09/23/2021<br>carol : 01/17/2020<br>alopez : 05/08/2017<br>carol : 03/28/2017<br>ckniffin : 03/23/2017<br>carol : 07/06/2015<br>mcolton : 6/30/2015<br>ckniffin : 6/29/2015<br>alopez : 2/12/2015<br>mcolton : 2/11/2015<br>ckniffin : 2/9/2015<br>carol : 7/26/2013<br>mgross : 7/17/2013<br>wwang : 6/22/2009<br>ckniffin : 6/8/2009<br>alopez : 1/4/2006<br>alopez : 12/30/2005<br>terry : 12/29/2005<br>wwang : 11/29/2005<br>ckniffin : 11/17/2005<br>mgross : 10/28/2003<br>joanna : 10/14/2003<br>mgross : 3/23/2001<br>mgross : 3/22/2001
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</span>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 605755
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</span>
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</h3>
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<div>
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<h3>
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<span class="mim-font">
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DOUBLECORTIN DOMAIN-CONTAINING PROTEIN 2; DCDC2
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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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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</p>
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<div>
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<h4>
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<span class="mim-font">
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RU2<br />
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RU2S
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</h4>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: DCDC2</em></strong>
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</span>
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</p>
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<strong>
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<em>
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Cytogenetic location: 6p22.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 6:24,171,755-24,383,292 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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<tbody>
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<td rowspan="3">
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<span class="mim-font">
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6p22.3
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<td>
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<span class="mim-font">
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?Deafness, autosomal recessive 66
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</span>
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</td>
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<td>
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<span class="mim-font">
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610212
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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<tr>
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<td>
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<span class="mim-font">
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Nephronophthisis 19
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</span>
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</td>
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<td>
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<span class="mim-font">
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616217
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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<tr>
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<td>
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<span class="mim-font">
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Sclerosing cholangitis, neonatal
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</span>
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</td>
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<td>
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<span class="mim-font">
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617394
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</tbody>
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</table>
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<br />
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The DCDC2 gene encodes a protein containing 2 doublecortin peptide domains similar to those in the doublecortin gene (DCX; 300121) (Meng et al., 2005). DCDC2 plays a role in the inhibition of canonical WNT (164820) signaling (Schueler et al., 2015). DCDC2 is a ciliary protein that binds tubulin and enhances microtubule polymerization (summary by Girard et al., 2016). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By screening cells expressing both HLA-B7 and kidney tumor cell RNA with autologous cytolytic T cells, followed by PCR, van den Eynde et al. (1999) obtained cDNAs encoding RU2, which is identical to the KIAA1154 gene identified by Hirosawa et al. (1999). Genomic sequence analysis determined that RU2 is transcribed as a 'normal' gene, resulting in a sense transcript (RU2S), and in the opposite direction, resulting in a shorter antisense transcript (RU2AS; 608211) found in tumors. Testing of synthetic peptides determined that the tumor antigen binding to HLA-B7 has the sequence LPRWPPPQL. Northern blot analysis revealed that the full-length gene is expressed as a 2.2-kb transcript. RT-PCR analysis detected ubiquitous expression of the full-length RU2S transcript, but expression of the RU2AS transcript was restricted to normal kidney, bladder, liver, and testis, as well as tumors of various histologic origins. The deduced RU2S protein contains 476 amino acids, while the RU2AS protein contains 84 residues. Van den Eynde et al. (1999) concluded that potentially useful antigens for cancer immunotherapy cannot be predicted from the sequence of the normal cellular protein. </p><p>Using RT-PCR and Northern blot analysis, Schumacher et al. (2006) demonstrated that DCDC2 is expressed in the adult and fetal central nervous system (CNS). </p><p>Using quantitative real-time RT-PCR of human brain, Meng et al. (2005) showed that DCDC2 exhibited highest expression in entorhinal cortex, inferior temporal cortex, medial temporal cortex, hypothalamus, amygdala, and hippocampus. </p><p>Schueler et al. (2015) found that DCDC2 colocalized with acetylated alpha-tubulin (see TUBA1A, 602529) at the axoneme of primary cilia of human renal tubule cells and cholangiocytes in liver, and to multiciliated ependymal cells and pia mater cells in mouse brain. However, DCDC2 did not localize to the basal body. </p><p>In postnatal rat and mouse inner ear, Grati et al. (2015) found that Dcdc2 localized to the kinocilia of inner, outer, and vestibular hair cells and to the primary cilia of all supporting cell types. It localized along the entire length, with increasing concentrations toward the tip. Dcdc2 was found in association with the cellular microtubule network. </p><p>Girard et al. (2016) found expression of DCDC2 in the cytoplasm and in cilia of cholangiocytes in liver bile ducts. Grammatikopoulos et al. (2016) found expression of the DCDC2 gene in cuboidal cholangiocytes in smaller intrahepatic bile ducts, with only faint focal marking in columnar cholangiocytes of larger and extrahepatic bile ducts. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Gene Structure</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
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<p><strong><em>DCDC2 Intron 2 Short Tandem Repeat BV677278</em></strong></p><p>
|
|
Within intron 2 of the DCDC2 gene, Meng et al. (2005) identified a 168-bp purine-rich region containing a polymorphic compound short tandem repeat (STR) composed of 10 alleles containing variable copy numbers of (GAGAGGAAGGAAA)n and (GGAA)n repeat units. Database analysis identified 131 putative transcription factor binding sites distributed throughout the purine-rich region, including multiple copies of binding sites for the brain-related transcription factors PEAS3 (ETV4; 600711) and NFATP (NFATC2; 600490). </p><p>Using electrophoretic mobility shift assays, Meng et al. (2011) showed that the conserved polymorphic purine-rich STR in intron 2 of the DCDC2 gene, which they called BV677278, bound nuclear proteins in a human brain lysate as well as in lymphoma cells. Expression of the 6 most common alleles of BV677278 in P19 cells, multipotent murine cells that can differentiate into neurons and neuroglia, showed that the alleles have a range of DCDC2-specific enhancer activities. The findings suggested that BV677278 alleles can modify DCDC2 expression to various degrees, which may link to changes in neural migration in the central nervous system. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Mapping</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
|
<p>Using FISH, van den Eynde et al. (1999) mapped the DCDC2 gene to chromosome 6p22.1. </p>
|
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</span>
|
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<div>
|
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In cellular studies, Schueler et al. (2015) found that DCDC2 fully or partially colocalized with acetylated alpha-tubulin to the spindle microtubules during metaphase and anaphase; to the abscission structure during late telophase/diakinesis; and to the ciliary axoneme in ciliated cells during interphase. Throughout those cell-cycle phases, DCDC2 was excluded from the basal body (in interphase), the mitotic spindle poles (in metaphase and anaphase), and the midbody (in diakinesis). Coimmunoprecipitation studies showed that DCDC2 interacted with DVL1 (601365), DVL2 (602151), and DVL3 (601368). DCDC2 also interacted with JIP1 (MAPK8IP1; 604641), which mediates MAPK signaling. Knockdown of DCDC2 increased beta-catenin (CTNNB1; 116806)-induced activation of T cell factor (TCF)-dependent transcription, and overexpression of DCDC2 reduced TCF-dependent transcription. These findings suggested that DCDC2 normally inhibits WNT signaling, and that loss of DCDC2 results in constitutive activation of the WNT signaling pathway. Knockdown of DCDC2 in a kidney cell culture system resulted in significantly fewer cilia compared to control, but the kidney cells formed normal spheroids without severe changes in lumen formation. Treatment of the DCDC2-null cells with a Wnt inhibitor restored the cilia defects. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Nephronophthisis 19</em></strong></p><p>
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In 2 unrelated patients with nephronophthisis-19 (NPHP19; 616217) with early-onset severe hepatic fibrosis, Schueler et al. (2015) identified homozygous or compound heterozygous truncating mutations in the DCDC2 gene (605755.0001-605755.0003). The mutation in the first patient was found by a combination of homozygosity mapping and whole-exome sequencing of 100 families with a similar disorder. The mutations in the subsequent patient were found by sequencing the DCDC2 gene in 800 families with a similar disorder. All mutations abrogated the normal inhibition of CTNNB1-induced activation of TCF-dependent transcription, resulting in increased WNT signaling. Cellular studies as well as studies in zebrafish showed that inhibition of the Wnt signaling pathway could rescue some of the defects associated with loss of dcdc2, suggesting a role for this pathway in the pathogenesis of NPHP19. </p><p>In a 13-year-old African Caribbean girl from Saint Vincent and the Grenadines with NPHP19, Slater et al. (2020) identified a homozygous nonsense mutation in the DCDC2 gene (S128X; 605755.0009). The DCDC2 gene was located in a 2.1-Mb area of homozygosity. In total, the patient was found to have 53 Mb of homozygosity, indicating identity by descent originating from a common ancestor between her parents. Functional studies were not performed. </p><p><strong><em>Autosomal Recessive Deafness 66</em></strong></p><p>
|
|
In affected members of a consanguineous Tunisian family with autosomal recessive deafness-66 (DFNB66; 610212), Grati et al. (2015) identified a homozygous missense mutation in the DCDC2 gene (Q424P; 605755.0004). The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family. Expression of mutant DCDC2a in hair cells and supporting cells caused cilium structural defects, and knockdown of the gene in zebrafish impaired hair cell survival and function. </p><p><strong><em>Neonatal Sclerosing Cholangitis</em></strong></p><p>
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|
In 4 patients from 2 unrelated consanguineous families with neonatal sclerosing cholangitis (NSC; 617394), Girard et al. (2016) identified 2 different homozygous mutations in the DCDC2 gene (605755.0005 and 605755.0006). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Patient cells showed loss of DCDC2 immunostaining in the ciliary axoneme of liver cholangiocytes and fewer cilia on cholangiocytes, as well as abnormal accumulation of the mutant protein in the cytoplasm compared to controls. </p><p>In 7 patients from 6 unrelated families, many of Greek origin, with NSC, Grammatikopoulos et al. (2016) identified homozygous or compound heterozygous truncating mutations in the DCDC2 gene (see, e.g., 605755.0001; 605755.0002; 605755.0007; 605755.0008). The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. Parental DNA was only available for 1 patient, but the results confirmed segregation of the mutations with the disorder within the family. Patient liver samples showed absence of DCDC2 expression, consistent with a complete loss of function, as well as absence of normally constituted primary cilia in cholangiocytes. The patients were part of a cohort of 12 families with the disorder who underwent whole-exome sequencing; direct sequencing of the DCDC2 gene in 10 patients from 8 additional families did not identify any mutations. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
|
|
For a discussion of a possible association between variation in the DCDC2 gene and dyslexia, see DYX2 (600202).</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Meng et al. (2005) demonstrated that Dcdc2 RNA interference introduced into cells at the cerebral ventricular zone of rat embryos resulted in altered neuronal migration. </p><p>Schueler et al. (2015) found that Dcdc2-null mice developed periportal hepatic fibrosis with biliary duct proliferation at age 11 months. Knockdown of the dcdc2 gene in zebrafish embryos resulted in typical ciliopathy-related morphologic defects, including ventrally curved body axis, hydrocephalus, kidney cysts, kinky tails, and occasional pericardial edema. Laterality defects were also observed. Treatment with iCRT14, an inhibitor of the Wnt signaling pathway, rescued some of the defects, but high concentrations were toxic to embryos. </p><p>Grati et al. (2015) found that morpholino knockdown of dcdc2b in zebrafish resulted in high levels of hair cell abnormalities, such as body deformations, and often in the internalization of the stereocilia hair bundles and their respective kinocilia, reflecting early steps of hair cell degeneration. There was a reduction in the number of saccular hair cells as well as a reduction of hair cell response to stimuli. Morpholino morphants were not capable of swimming or hearing. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>9 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0001 NEPHRONOPHTHISIS 19</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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SCLEROSING CHOLANGITIS, NEONATAL, INCLUDED
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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DCDC2, LYS217TER
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<br />
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SNP: rs730880299,
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ClinVar: RCV000157642, RCV000477678
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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 />
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<p><strong><em>Nephronophthisis 19</em></strong></p><p>
|
|
In a patient, born of consanguineous parents, with nephronophthisis-19 (NPHP19; 616217), Schueler et al. (2015) identified a homozygous c.649A-T transversion (c.649A-T, NM_001195610.1) in exon 6 of the DCDC2 gene, resulting in a lys217-to-ter (K217X) substitution within the second doublecortin domain. The mutation was found by homozygosity mapping and whole-exome sequencing. In vitro cellular immunohistochemical studies showed that mutant DCDC2 failed to localize properly to primary cilia. The mutant protein was unable to rescue ciliopathy-related morphologic defects in dcdc2-null zebrafish, consistent with a loss of function. </p><p><strong><em>Sclerosing Cholangitis, Neonatal</em></strong></p><p>
|
|
In a girl (patient 1), born of consanguineous parents of Asian descent, with neonatal sclerosing cholangitis (NSC; 617394), Grammatikopoulos et al. (2016) identified homozygosity for the K217X mutation in the DCDC2 gene. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was filtered against the 1000 Genomes Project and Exome Sequencing Project databases. Parental DNA was not available for segregation analysis. Patient liver samples showed absence of DCDC2 expression, consistent with a complete loss of function, as well as absence of normally constituted primary cilia in cholangiocytes. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0002 NEPHRONOPHTHISIS 19</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">
|
|
SCLEROSING CHOLANGITIS, NEONATAL, INCLUDED
|
|
</span>
|
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</div>
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<div>
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<span class="mim-text-font">
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DCDC2, 2-BP DEL, 123GT
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<br />
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|
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SNP: rs757704417,
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gnomAD: rs757704417,
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|
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ClinVar: RCV000157643, RCV000477717, RCV001335811, RCV002498782, RCV002515058
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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 />
|
|
<p><strong><em>Nephronophthisis 19</em></strong></p><p>
|
|
In a Czech patient with nephronophthisis-19 (NPHP19; 616217), Schueler et al. (2015) identified compound heterozygous mutations in the DCDC2 gene: a 2-bp deletion (c.123_124delGT, NM_001195610.1) in exon 2, resulting in a frameshift and premature termination (Ser42GlnfsTer72) within the first doublecortin domain, and an A-to-G transition in intron 3 (c.349-2A-G; 605755.0003), resulting in a splicing defect, a frameshift, and premature termination (Val117LeufsTer54). The patient was ascertained from a larger cohort of 800 families with NPHP-related ciliopathies who underwent direct sequencing of the DCDC2 gene. In vitro cellular immunohistochemical studies showed that mutant DCDC2 failed to localize properly to primary cilia. Expression of the deletion mutation was unable to rescue ciliopathy-related morphologic defects in dcdc2-null zebrafish, consistent with a loss of function. </p><p><strong><em>Sclerosing Cholangitis, Neonatal</em></strong></p><p>
|
|
In an 18-year-old Caucasian man (patient 6), born of unrelated parents, with neonatal sclerosing cholangitis (NSC; 617394), Grammatikopoulos et al. (2016) identified homozygosity for the c.123_124delGT mutation in the DCDC2 gene. Another patient (patient 5) with NSC2 was compound heterozygous for the c.123_124delGT mutation and a nonsense mutation (L297X; 605755.0007). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, were filtered against the 1000 Genomes Project and Exome Sequencing Project databases. Parental DNA for patient 6 was not available for segregation analysis, but the unaffected parents of patient 5 were each heterozygous for 1 of the mutations. Patient liver samples showed absence of DCDC2 expression, consistent with a complete loss of function, as well as absence of normally constituted primary cilia in cholangiocytes. </p>
|
|
</span>
|
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</div>
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<div>
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<br />
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|
</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 NEPHRONOPHTHISIS 19</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
|
DCDC2, IVS3AS, A-G, -2
|
|
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|
|
|
<br />
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|
|
SNP: rs760040426,
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|
|
|
gnomAD: rs760040426,
|
|
|
|
|
|
ClinVar: RCV000157644, RCV000731261, RCV001850190, RCV002498783
|
|
|
|
|
|
</span>
|
|
</div>
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.349-2A-G mutation (c.349-2A-G, NM_001195610.1) in the DCDC2 gene that was found in compound heterozygous state in a patient with nephronophthisis-19 (NPHP19; 616217) by Schueler et al. (2015), see 605755.0002. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
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|
</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 DEAFNESS, AUTOSOMAL RECESSIVE 66 (1 family)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCDC2, GLN424PRO
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|
|
|
|
|
<br />
|
|
|
|
SNP: rs794729665,
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|
|
|
|
|
|
|
ClinVar: RCV000157618, RCV000185587
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a consanguineous Tunisian family with autosomal recessive deafness-66 (DFNB66; 610212), originally reported by Tlili et al. (2005), Grati et al. (2015) identified a homozygous c.1271A-C transversion (c.1271A-C, NM_001195610) in the DCDC2 gene, resulting in a gln424-to-pro (Q424P) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family and was not found in the dbSNP (build 37), 1000 Genomes Project, or Exome Sequencing Project databases, or in 435 ancestry-matched controls. Overexpression of both wildtype and mutant DCDC2 in COS-7 cells disrupted the intracellular microtubule network by inducing the formation of extended cytosolic microtubule cables. In rat hair cells, Q424P caused a 2- to 3-fold increase in cilia length compared to wildtype, as well as other ciliary abnormalities, such as branching, duplication, and triplication, and stereocilia bundle degeneration. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 SCLEROSING CHOLANGITIS, NEONATAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCDC2, LYS17ASN
|
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|
|
|
|
<br />
|
|
|
|
SNP: rs1042640142,
|
|
|
|
|
|
|
|
ClinVar: RCV000477748
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 brothers, born of consanguineous parents, with neonatal sclerosing cholangitis (NSC; 617394), Girard et al. (2016) identified a homozygous c.51G-C transversion (c.51G-C, NM_016356.3) in exon 1 of the DCDC2 gene, resulting in a lys17-to-asn (K17N) substitution at a highly conserved residue at the beginning of the first doublecortin domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the dbSNP, 1000 Genomes Project, Exome Variant Server, or ExAC databases, or in an in-house database of 7,477 exomes. Patient cells showed loss of DCDC2 immunostaining in the ciliary axoneme of liver cholangiocytes and fewer cilia on cholangiocytes, as well as abnormal accumulation of the mutant protein in the cytoplasm compared to controls. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 SCLEROSING CHOLANGITIS, NEONATAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCDC2, 132-BP DEL, NT426
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000477686
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs, born of consanguineous parents, with neonatal sclerosing cholangitis (NSC; 617394), Girard et al. (2016) identified a homozygous 132-bp deletion (c.426_557del, NM_016356.3) in the DCDC2 gene, resulting in an in-frame deletion of 14 residues (Phe142_Arg186del) encompassing the entire exon 4 within the second doublecortin domain. The mutation, which was found by ciliary gene-targeting sequencing, segregated with the disorder in the family. It was not found in the dbSNP, 1000 Genomes Project, Exome Variant Server, or ExAC databases, or in an in-house database of 7,477 exomes. PCR analysis of patient cells confirmed the deletion. Patient cells showed loss of DCDC2 immunostaining in the ciliary axoneme of liver cholangiocytes and fewer cilia on cholangiocytes, as well as abnormal accumulation of the mutant protein in the cytoplasm compared to controls. </p>
|
|
</span>
|
|
</div>
|
|
|
|
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|
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<div>
|
|
<br />
|
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</div>
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|
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</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 SCLEROSING CHOLANGITIS, NEONATAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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|
DCDC2, LEU297TER
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|
|
<br />
|
|
|
|
SNP: rs1050411259,
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|
|
|
|
|
gnomAD: rs1050411259,
|
|
|
|
|
|
ClinVar: RCV000477711, RCV002475927, RCV002525737
|
|
|
|
|
|
</span>
|
|
</div>
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|
|
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 12-year-old girl of Greek descent (patient 2) neonatal sclerosing cholangitis (NSC; 617394), Grammatikopoulos et al. (2016) identified a homozygous c.890T-A transversion (c.890T-A, NM_001195610) in exon 7 of the DCDC2 gene, resulting in a leu297-to-ter (L297X) substitution. Three additional patients from 2 families were compound heterozygous for L297X and another pathogenic DCDC2 mutation: 1 Greek patient (patient 5) carried a 2-bp deletion (c.123_124delGT; 605755.0002) on the other allele, whereas 2 Greek sibs (patients 4 and 7) carried a 1-bp duplication in exon 4 (c.529dupA; 605755.0008), resulting in a frameshift and premature termination (Ile177AsnfsTer20), on the other allele. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, were filtered against the 1000 Genomes Project and Exome Sequencing Project databases. Parental DNA was not available for segregation analysis for the sibs, but each unaffected parent of patient 5 was heterozygous for 1 of the mutations. Patient liver samples showed absence of DCDC2 expression, consistent with a complete loss of function, as well as absence of normally constituted primary cilia in cholangiocytes. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
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|
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</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 SCLEROSING CHOLANGITIS, NEONATAL</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
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DCDC2, 1-BP DUP, 529A
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<br />
|
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|
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SNP: rs904944428,
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gnomAD: rs904944428,
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|
|
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ClinVar: RCV000477740, RCV000593742, RCV000692639, RCV005034007
|
|
|
|
|
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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 1-bp duplication (c.529dupA, NM_001195610) in exon 4 of the DCDC2 gene, resulting in a frameshift and premature termination (Ile177AsnfsTer20), that was found in compound heterozygous state in 2 sibs with neonatal sclerosing cholangitis (NSC; 617394) by Grammatikopoulos et al. (2016), see 605755.0007. </p>
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<strong>.0009 NEPHRONOPHTHISIS 19</strong>
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DCDC2, SER128TER ({dbSNP rs904520404})
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SNP: rs904520404,
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gnomAD: rs904520404,
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ClinVar: RCV000595112, RCV001722542, RCV002491217
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<p>In a 13-year-old African Caribbean girl from Saint Vincent and the Grenadines with nephronophthisis-19 (NPHP19; 616217), Slater et al. (2020) identified homozygosity for a c.383C-G transversion in exon 3 the DCDC2 gene, resulting in a ser128-to-ter (S128X) substitution. The mutation was identified by whole-exome sequencing. The DCDC2 gene was located in a 2.1-Mb area of homozygosity. In total, the patient was found to have 53 Mb of homozygosity, indicating identity by descent originating from a common ancestor between her parents. Functional studies were not performed. The patient also had psychiatric features, and the authors noted that the patient had variants of unknown significance in 5 other genes that were possibly related to the clinical phenotype. </p>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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Girard, M., Bizet, A. A., Lachaux, A., Gonzales, E., Filhol, E.,Collardeau-Frachon, S., Jeanpierre, C., Henry, C., Fabre, M., Viremouneix, L., Galmiche, L., Debray, D., and 10 others.
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<strong>DCDC2 mutations cause neonatal sclerosing cholangitis.</strong>
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Hum. Mutat. 37: 1025-1029, 2016.
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[PubMed: 27319779]
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[Full Text: https://doi.org/10.1002/humu.23031]
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Grammatikopoulos, T., Sambrotta, M., Strautnieks, S., Foskett, P., Knisely, A. S., Wagner, B., Deheragoda, M., Starling, C., Mieli-Vergani, G., Smith, J., University of Washington Center for Mendelian Genomics, Bull, L., Thompson, R. J.
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<strong>Mutations in DCDC2 (doublecortin domain containing protein 2) in neonatal sclerosing cholangitis.</strong>
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J. Hepatol. 65: 1179-1187, 2016.
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[PubMed: 27469900]
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[Full Text: https://doi.org/10.1016/j.jhep.2016.07.017]
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Grati, M., Chakchouk, I., Ma, Q., Bensaid, M., Desmidt, A., Turki, N., Yan, D., Baanannou, A., Mittal, R., Driss, N., Blanton, S., Farooq, A., Lu, Z., Liu, X. Z., Masmoudi, S.
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<strong>A missense mutation in DCDC2 causes human recessive deafness DFNB66, likely by interfering with sensory hair cell and supporting cell cilia length regulation.</strong>
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Hum. Molec. Genet. 24: 2482-2491, 2015.
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[PubMed: 25601850]
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[Full Text: https://doi.org/10.1093/hmg/ddv009]
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<p class="mim-text-font">
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Hirosawa, M., Nagase, T., Ishikawa, K., Kikuno, R., Nomura, N., Ohara, O.
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<strong>Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain.</strong>
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DNA Res. 6: 329-336, 1999.
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[PubMed: 10574461]
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[Full Text: https://doi.org/10.1093/dnares/6.5.329]
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Meng, H., Powers, N. R., Tang, L., Cope, N. A., Zhang, P.-X., Fuleihan, R., Gibson, C., Page, G. P., Gruen, J. R.
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<strong>A dyslexia-associated variant in DCDC2 changes gene expression.</strong>
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Behav. Genet. 41: 58-66, 2011.
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[PubMed: 21042874]
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[Full Text: https://doi.org/10.1007/s10519-010-9408-3]
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Meng, H., Smith, S. D., Hager, K., Held, M., Liu, J., Olson, R. K., Pennington, B. F., DeFries, J. C., Gelernter, J., O'Reilly-Pol, T., Somlo, S., Skudlarski, P., Shaywitz, S. E., Shaywitz, B. A., Marchione, K., Wang, Y., Paramasivam, M., LoTurco, J. J., Page, G. P., Gruen, J. R.
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<strong>DCDC2 is associated with reading disability and modulates neuronal development in the brain.</strong>
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Proc. Nat. Acad. Sci. 102: 17053-17058, 2005. Note: Erratum: Proc. Nat. Acad. Sci. 102: 18763 only, 2005.
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[PubMed: 16278297]
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[Full Text: https://doi.org/10.1073/pnas.0508591102]
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Schueler, M., Braun, D. A., Chandrasekar, G., Gee, H. Y., Klasson, T. D., Halbritter, J., Bieder, A., Porath, J. D., Airik, R., Zhou, W., LoTurco, J. J., Che, A., and 17 others.
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<strong>DCDC2 mutations cause a renal-hepatic ciliopathy by disrupting Wnt signaling.</strong>
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Am. J. Hum. Genet. 96: 81-92, 2015.
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[PubMed: 25557784]
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[Full Text: https://doi.org/10.1016/j.ajhg.2014.12.002]
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Schumacher, J., Anthoni, H., Dahdouh, F., Konig, I. R., Hillmer, A. M., Kluck, N., Manthey, M., Plume, E., Warnke, A., Remschmidt, H., Hulsmann, J., Cichon, S., Lindgren, C. M., Propping, P., Zucchelli, M., Ziegler, A., Peyrard-Janvid, M., Schulte-Korne, G., Nothen, M. M., Kere, J.
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<strong>Strong genetic evidence of DCDC2 as a susceptibility gene for dyslexia.</strong>
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Am. J. Hum. Genet. 78: 52-62, 2006.
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[PubMed: 16385449]
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[Full Text: https://doi.org/10.1086/498992]
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Slater, B., Bekheirnia, N., Angelo, J., Bi, W., Braun, M. C., Bekheirnia, M. R.
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<strong>Nephronophthisis due to a novel DCDC2 variant in a patient from African-Caribbean descent: a case report.</strong>
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Am. J. Med. Genet. 182A: 527-531, 2020.
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[PubMed: 31821705]
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[Full Text: https://doi.org/10.1002/ajmg.a.61440]
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Tlili, A., Mannikko, M., Charfedine, I., Lahmar, I., Benzina, Z., Ben Amor, M., Driss, N., Ala-Kokko, L., Drira, M., Masmoudi, S., Ayadi, H.
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<strong>A novel autosomal recessive non-syndromic deafness locus, DFNB66, maps to chromosome 6p21.2-22.3 in a large Tunisian consanguineous family.</strong>
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Hum. Hered. 60: 123-128, 2005.
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[PubMed: 16244493]
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[Full Text: https://doi.org/10.1159/000088974]
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van den Eynde, B. J., Gaugler, B., Probst-Kepper, M., Michaux, L., Devuyst, O., Lorge, F., Weynants, P., Boon, T.
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<strong>A new antigen recognized by cytolytic T lymphocytes on a human kidney tumor results from reverse strand transcription.</strong>
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J. Exp. Med. 190: 1793-1799, 1999.
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[PubMed: 10601354]
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[Full Text: https://doi.org/10.1084/jem.190.12.1793]
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Hilary J. Vernon - updated : 09/23/2021<br>Cassandra L. Kniffin - updated : 03/23/2017<br>Cassandra L. Kniffin - updated : 6/29/2015<br>Cassandra L. Kniffin - updated : 2/9/2015<br>Matthew B. Gross - updated : 7/17/2013<br>Victor A. McKusick - updated : 12/29/2005<br>Cassandra L. Kniffin - updated : 11/17/2005
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