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- *609412 - ERCC EXCISION REPAIR 8, CSA UBIQUITIN LIGASE COMPLEX SUBUNIT; ERCC8
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<p>
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<span class="h4">*609412</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#history">History</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/609412">Table View</a>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></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 role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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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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<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 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-heading mim-panel-heading" role="tab" id="mimGenome">
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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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</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=ENSG00000049167;t=ENST00000676185" 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=1161" 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=609412" 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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<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=ENSG00000049167;t=ENST00000676185" 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_000082,NM_001007233,NM_001007234,NM_001290285" 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_000082" 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=609412" 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=07523&isoform_id=07523_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/ERCC8" 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/975302,3121917,4557467,14602565,27802687,49168610,54696904,55956770,55956773,119575398,119575399,119575400,158254888,189069445,193787006,194378420,194388022,590122050,957949133,957949140" 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/Q13216" 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=1161" 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=ENSG00000049167;t=ENST00000676185" 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=ERCC8" 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=ERCC8" 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+1161" 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/ERCC8" 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:1161" 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/1161" 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=chr5&hgg_gene=ENST00000676185.1&hgg_start=60866454&hgg_end=60945070&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:3439" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:3439" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/ercc8" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=609412[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=609412[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/ERCC8/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/ENSG00000049167" 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=ERCC8" 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=ERCC8" 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=ERCC8" 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=ERCC8&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/PA27853" 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:3439" 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:1919241" 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/ERCC8#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:1919241" 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/1161/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=1161" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00008403;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-041010-60" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:1161" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=ERCC8&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 890433006<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
|
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609412
|
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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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ERCC EXCISION REPAIR 8, CSA UBIQUITIN LIGASE COMPLEX SUBUNIT; ERCC8
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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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
EXCISION REPAIR CROSS-COMPLEMENTING, GROUP 8<br />
|
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CSA GENE<br />
|
|
CKN1 GENE
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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=ERCC8" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ERCC8</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/5/193?start=-3&limit=10&highlight=193">5q12.1</a>
|
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr5:60866454-60945070&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'})">5:60,866,454-60,945,070</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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</span>
|
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</p>
|
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</div>
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<div>
|
|
<br />
|
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</div>
|
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<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=216400,614621" 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>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/5/193?start=-3&limit=10&highlight=193">
|
|
5q12.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Cockayne syndrome, type A
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/216400"> 216400 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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|
|
</span>
|
|
</td>
|
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</tr>
|
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|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
UV-sensitive syndrome 2
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/614621"> 614621 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
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<p>The ERCC8 gene is part of the nucleotide excision repair (NER) pathway, a complex system that eliminates a broad spectrum of structural DNA lesions, including ultraviolet (UV)-induced cyclobutane pyrimidine dimers, bulky chemical adducts, and DNA cross-links. One of the NER pathways preferentially repairs lesions on the transcribed strand of active genes; this process occurs more rapidly than repairs on nontranscribed strands that are part of overall genome repair (<a href="#13" class="mim-tip-reference" title="Troelstra, C., van Gool, A., de Wit, J., Vermeulen, W., Bootsma, D., Hoeijmakers, J. H. J. <strong>ERCC6, a member of a subfamily of putative helicases, is involved in Cockayne's syndrome and preferential repair of active genes.</strong> Cell 71: 939-953, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1339317/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1339317</a>] [<a href="https://doi.org/10.1016/0092-8674(92)90390-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1339317">Troelstra et al., 1992</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1339317" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#7" class="mim-tip-reference" title="Henning, K. A., Li, L., Iyer, N., McDaniel, L. D., Reagan, M. S., Legerski, R., Schultz, R. A., Stefanini, M., Lehmann, A. R., Mayne, L. V., Friedberg, E. C. <strong>The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CSB protein and a subunit of RNA polymerase II TFIIH.</strong> Cell 82: 555-564, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7664335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7664335</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90028-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7664335">Henning et al. (1995)</a> cloned the human CKN1 gene, which they called CSA, by functional complementation of cells derived from patients with Cockayne syndrome A (CSA; <a href="/entry/216400">216400</a>). They found that the CSA cDNA uniquely and specifically corrected UV sensitivity in CSA cells. The predicted 396-amino acid protein has a calculated molecular mass of approximately 44 kD and contains a WD repeat (WD40 repeat) domain as reviewed by <a href="#11" class="mim-tip-reference" title="Neer, E. J., Schmidt, C. J., Nambudripad, R., Smith, T. F. <strong>The ancient regulatory-protein family of WD-repeat proteins.</strong> Nature 371: 297-300, 1994. Note: Erratum: Nature 371: 812 only, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8090199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8090199</a>] [<a href="https://doi.org/10.1038/371297a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8090199">Neer et al. (1994)</a>. In vitro translated CSA protein specifically interacted with the CSB (ERCC6; <a href="/entry/609413">609413</a>) protein and p44 protein (GTF2H2; <a href="/entry/601748">601748</a>), a subunit of the RNA polymerase II basal transcription factor TFIIH (see also <a href="/entry/189972">189972</a>). These observations, coupled with the observation that the amino acid sequence of the predicted CSB polypeptide is homologous with a component of the yeast Swi/Snf transcriptional activation complex, suggested that Cockayne syndrome cells are defective in RNA polymerase II transcription. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8090199+7664335" 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 Southern blot hybridization in human/rodent hybrid cell DNA, <a href="#7" class="mim-tip-reference" title="Henning, K. A., Li, L., Iyer, N., McDaniel, L. D., Reagan, M. S., Legerski, R., Schultz, R. A., Stefanini, M., Lehmann, A. R., Mayne, L. V., Friedberg, E. C. <strong>The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CSB protein and a subunit of RNA polymerase II TFIIH.</strong> Cell 82: 555-564, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7664335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7664335</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90028-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7664335">Henning et al. (1995)</a> mapped the CSA gene to chromosome 5. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7664335" 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>Damage to actively transcribed DNA is preferentially repaired by the transcription-coupled repair (TCR) system, which requires RNA polymerase II (pol II). <a href="#2" class="mim-tip-reference" title="Bregman, D. B., Halaban, R., van Gool, A. J., Henning, K. A., Friedberg, E. C., Warren, S. L. <strong>UV-induced ubiquitination of RNA polymerase II: a novel modification deficient in Cockayne syndrome cells.</strong> Proc. Nat. Acad. Sci. 93: 11586-11590, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8876179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8876179</a>] [<a href="https://doi.org/10.1073/pnas.93.21.11586" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8876179">Bregman et al. (1996)</a> demonstrated that a fraction of the large subunit of pol II (POL2R; <a href="/entry/180660">180660</a>) was ubiquitinated after exposing cells to UV-radiation or cisplatin but not several other DNA-damaging agents. This novel covalent modification of POL2R occurred within 15 minutes of exposing cells to UV-radiation and persisted for about 8 to 12 hours. Ubiquitinated POL2R was also phosphorylated on the C-terminal domain. UV-induced ubiquitination of POL2R was deficient in fibroblasts from persons with either Cockayne syndrome A or B (<a href="/entry/133540">133540</a>). In both of these disorders, transcription-coupled repair is disrupted. UV-induced ubiquitination of POL2R could be restored by introducing cDNA constructs encoding the CSA or CSB genes, respectively, into CSA or CSB fibroblasts. These results suggested that ubiquitination of POL2R plays a role in the recognition and/or repair of damage to actively transcribed genes. Alternatively, these findings may reflect a role played by the CSA and CSB gene products in transcription, a possibility that had been suggested on other grounds. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8876179" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="van Gool, A. J., van der Horst, G. T. J., Citterio, E., Hoeijmakers, J. H. J. <strong>Cockayne syndrome: defective repair of transcription?</strong> EMBO J. 16: 4155-4162, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9250659/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9250659</a>] [<a href="https://doi.org/10.1093/emboj/16.14.4155" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9250659">Van Gool et al. (1997)</a> noted that there is evidence that basic metabolic processes within the cell are intimately linked and influenced by one another. One such link is the close interplay between nucleotide excision DNA repair and transcription, as illustrated both by the preferential repair of the transcribed strand of active genes (TCR) and by the distinct dual involvement of proteins in both processes. In E. coli, 1 protein, the transcription repair-coupling factor, accomplishes the dual function. On the basis of experimental observations, <a href="#14" class="mim-tip-reference" title="van Gool, A. J., van der Horst, G. T. J., Citterio, E., Hoeijmakers, J. H. J. <strong>Cockayne syndrome: defective repair of transcription?</strong> EMBO J. 16: 4155-4162, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9250659/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9250659</a>] [<a href="https://doi.org/10.1093/emboj/16.14.4155" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9250659">van Gool et al. (1997)</a> suggested that the situation in eukaryotes is more complex, involving dual functionality of multiple proteins. They suggested that Cockayne syndrome may represent a defect in TCR. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9250659" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By immunoprecipitation analysis of HeLa cells, <a href="#6" class="mim-tip-reference" title="Groisman, R., Polanowska, J., Kuraoka, I., Sawada, J., Saijo, M., Drapkin, R., Kisselev, A. F., Tanaka, K., Nakatani, Y. <strong>The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage.</strong> Cell 113: 357-367, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12732143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12732143</a>] [<a href="https://doi.org/10.1016/s0092-8674(03)00316-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12732143">Groisman et al. (2003)</a> identified DDB2 (<a href="/entry/600811">600811</a>) and CSA as components of similar but distinct protein complexes. Both DDB2 and CSA interacted with DDB1 (<a href="/entry/600045">600045</a>), a component of both complexes. Cullin-4A (CUL4A; <a href="/entry/603137">603137</a>), ROC1 (RBX1; <a href="/entry/603814">603814</a>), and all the subunits of the COP9 signalosome (e.g., COPS2; <a href="/entry/604508">604508</a>) were also present in both complexes. Following UV irradiation, the DDB2 complex bound tightly to chromatin in a UV-dependent manner and initiated global genome repair, whereas the CSA complex bound to RNA polymerase II and initiated TCR. The COP9 signalosome in each complex differentially regulated cullin-based ubiquitin ligase activity in response to UV irradiation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12732143" 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="#7" class="mim-tip-reference" title="Henning, K. A., Li, L., Iyer, N., McDaniel, L. D., Reagan, M. S., Legerski, R., Schultz, R. A., Stefanini, M., Lehmann, A. R., Mayne, L. V., Friedberg, E. C. <strong>The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CSB protein and a subunit of RNA polymerase II TFIIH.</strong> Cell 82: 555-564, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7664335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7664335</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90028-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7664335">Henning et al. (1995)</a> identified mutations in the ERCC8 gene in CSA cDNAs of all CSA cell lines examined, including an identical mutation in 2 CSA sibs (<a href="#0001">609412.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7664335" 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 cell line from an 11-year-old girl with CSA, <a href="#3" class="mim-tip-reference" title="Cao, H., Williams, C., Carter, M., Hegele, R. A. <strong>CKN1 (MIM 216400): mutations in Cockayne syndrome type A and a new common polymorphism.</strong> J. Hum. Genet. 49: 61-63, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14661080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14661080</a>] [<a href="https://doi.org/10.1007/s10038-003-0107-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14661080">Cao et al. (2004)</a> identified compound heterozygosity for a nonsense mutation (E13X; <a href="#0003">609412.0003</a>) and a missense mutation (A205P; <a href="#0005">609412.0005</a>) in the ERCC8 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14661080" 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 cell line from a patient with CSA, <a href="#12" class="mim-tip-reference" title="Ridley, A. J., Colley, J., Wynford-Thomas, D., Jones, C. J. <strong>Characterisation of novel mutations in Cockayne syndrome type A and xeroderma pigmentosum group C subjects.</strong> J. Hum. Genet. 50: 151-154, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15744458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15744458</a>] [<a href="https://doi.org/10.1007/s10038-004-0228-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15744458">Ridley et al. (2005)</a> identified compound heterozygosity for an E13X mutation and a novel missense mutation (A160V; <a href="#0004">609412.0004</a>) in the ERCC8 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15744458" 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="Bertola, D. R., Cao, H., Albano, L. M. J., Oliveira, D. P., Kok, F., Marques-Dias, M. J., Kim, C. A., Hegele, R. A. <strong>Cockayne syndrome type A: novel mutations in eight typical patients.</strong> J. Hum. Genet. 51: 701-705, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16865293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16865293</a>] [<a href="https://doi.org/10.1007/s10038-006-0011-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16865293">Bertola et al. (2006)</a> analyzed the ERCC8 gene in 8 patients from 6 Brazilian families with typical CSA and identified homozygosity or compound heterozygosity for ERCC8 mutations in all of them. The authors stated that there was no obvious genotype/phenotype correlation across the mutation spectrum. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16865293" 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>UV-Sensitive Syndrome 2</em></strong></p><p>
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In a 15-year-old French girl with UV-sensitive syndrome-2 (UVSS2; <a href="/entry/614621">614621</a>), <a href="#10" class="mim-tip-reference" title="Nardo, T., Oneda, R., Spivak, G., Vaz, B., Mortier, L., Thomas, P., Orioli, D., Laugel, V., Stary, A., Hanawalt, P. C., Sarasin, A., Stefanini, M. <strong>A UV-sensitive syndrome patient with a specific CSA mutation reveals separable roles for CSA in response to UV and oxidative DNA damage.</strong> Proc. Nat. Acad. Sci. 106: 6209-6214, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19329487/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19329487</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19329487[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.0902113106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19329487">Nardo et al. (2009)</a> identified a homozygous mutation in the ERCC8 gene (W361C; <a href="#0006">609412.0006</a>). She had sun sensitivity and freckling, but no other abnormalities. Patient-derived fibroblasts showed a reduced recovery of RNA synthesis after UV irradiation and a defective capacity to repair UV-induced damage on the transcribed strand of active genes, indicating a defect in transcription-coupled nucleotide excision repair (TC-NER). However, there was no hypersensitivity to reactive oxygen species, and UV-induced DNA repair synthesis and global genome NER (GG-NER) were normal. <a href="#10" class="mim-tip-reference" title="Nardo, T., Oneda, R., Spivak, G., Vaz, B., Mortier, L., Thomas, P., Orioli, D., Laugel, V., Stary, A., Hanawalt, P. C., Sarasin, A., Stefanini, M. <strong>A UV-sensitive syndrome patient with a specific CSA mutation reveals separable roles for CSA in response to UV and oxidative DNA damage.</strong> Proc. Nat. Acad. Sci. 106: 6209-6214, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19329487/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19329487</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19329487[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.0902113106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19329487">Nardo et al. (2009)</a> hypothesized that the mild phenotype in this patient was due to the lack of cellular sensitivity to oxidative stress. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19329487" 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>The article by <a href="#5" class="mim-tip-reference" title="Fousteri, M., Vermeulen, W., van Zeeland, A. A., Mullenders, L. H. F. <strong>Cockayne syndrome A and B proteins differentially regulate recruitment of chromatin remodeling and repair factors to stalled RNA polymerase II in vivo.</strong> Molec. Cell 23: 471-482, 2006. Note: Retraction: Molec. Cell 81: 5112 only, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16916636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16916636</a>] [<a href="https://doi.org/10.1016/j.molcel.2006.06.029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16916636">Fousteri et al. (2006)</a> regarding the function of CSB and CSA in TCR complex formation was retracted because an investigation at the Leiden University Medical Center concluded that 'unacceptable data manipulation' by one of the authors 'led to breaches of scientific integrity, making these results unreliable.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16916636" 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 2 sibs, born of consanguineous parents, with Cockayne syndrome A (<a href="/entry/216400">216400</a>), <a href="#7" class="mim-tip-reference" title="Henning, K. A., Li, L., Iyer, N., McDaniel, L. D., Reagan, M. S., Legerski, R., Schultz, R. A., Stefanini, M., Lehmann, A. R., Mayne, L. V., Friedberg, E. C. <strong>The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CSB protein and a subunit of RNA polymerase II TFIIH.</strong> Cell 82: 555-564, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7664335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7664335</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90028-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7664335">Henning et al. (1995)</a> identified 2 deletions in the ERCC8 gene. One deletion removed 279 bp from the CKN1 coding region, starting at nucleotide 880 of their sequence and ending at nucleotide 1158. A second deletion of 81 bp in the CKN1 region started at nucleotide position 1078 and also ended at nucleotide position 1158. The fact that the deletions identified in both cDNAs from both sibs ended at the identical nucleotide positions strongly suggested to the authors that this nucleotide marks an exon/intron junction and the truncated cDNAs represent abnormally spliced products missing either 1 (81 bp) or 2 (279 bp) upstream exons. These abnormal splice products presumably derived from a homozygous mutation in a splice donor site. Neither deletion created a frameshift. Hence, the 2 abnormal transcripts potentially encode internally deleted proteins with predicted sizes of 303 and 369 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7664335" 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> rs121434323 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434323;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/rs121434323?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=rs121434323" 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=rs121434323" 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=RCV000001785 OR RCV001388976 OR RCV003330380" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001785, RCV001388976, RCV003330380" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001785...</a>
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<p>In a cell line derived from a patient with Cockayne syndrome A (<a href="/entry/216400">216400</a>), <a href="#7" class="mim-tip-reference" title="Henning, K. A., Li, L., Iyer, N., McDaniel, L. D., Reagan, M. S., Legerski, R., Schultz, R. A., Stefanini, M., Lehmann, A. R., Mayne, L. V., Friedberg, E. C. <strong>The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CSB protein and a subunit of RNA polymerase II TFIIH.</strong> Cell 82: 555-564, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7664335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7664335</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90028-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7664335">Henning et al. (1995)</a> identified a C-to-A transversion in the ERCC8 gene, resulting in a tyr322-to-ter (Y322X) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7664335" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="McDaniel, L. D., Legerski, R., Lehmann, A. R., Friedberg, E. C., Schultz, R. A. <strong>Confirmation of homozygosity for a single nucleotide substitution mutation in a Cockayne syndrome patient using monoallelic mutation analysis in somatic cell hybrids.</strong> Hum. Mutat. 10: 317-321, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9338586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9338586</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1997)10:4<317::AID-HUMU8>3.0.CO;2-D" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9338586">McDaniel et al. (1997)</a> demonstrated that the Y322X mutation was present in homozygous state, using a strategy with general applicability. Somatic cell hybrids were established by fusing patient cells with mouse A9 cells. Screening with chromosome 5-specific polymorphic markers facilitated identification of hybrid clones bearing only 1 of the distinct CSA alleles. Sequencing a portion of the human CSA gene in a subset of these hybrids permitted monoallelic mutation analysis and confirmed the presence of the Y322X mutation in both alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9338586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Khayat, M., Hardouf, H., Zlotogora, J., Shalev, S. A. <strong>High carriers frequency of an apparently ancient founder mutation p.Tyr322X in the ERCC8 gene responsible for Cockayne syndrome among Christian Arabs in northern Israel.</strong> Am. J. Med. Genet. 152A: 3091-3094, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21108394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21108394</a>] [<a href="https://doi.org/10.1002/ajmg.a.33746" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21108394">Khayat et al. (2010)</a> analyzed the Y322X mutation in the Arab Christian population of northern Israel and found a carrier frequency of 6.79. Haplotype analysis as well as the high carrier frequency suggested that Y322X is an ancient founder mutation that may have originated in the Christian Lebanese community. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21108394" 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> rs121434324 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434324;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/rs121434324?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=rs121434324" 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=rs121434324" 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=RCV000001786 OR RCV001064361 OR RCV001280547 OR RCV002490294" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001786, RCV001064361, RCV001280547, RCV002490294" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001786...</a>
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<p>In a cell line from a patient with Cockayne syndrome A (<a href="/entry/216400">216400</a>), <a href="#3" class="mim-tip-reference" title="Cao, H., Williams, C., Carter, M., Hegele, R. A. <strong>CKN1 (MIM 216400): mutations in Cockayne syndrome type A and a new common polymorphism.</strong> J. Hum. Genet. 49: 61-63, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14661080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14661080</a>] [<a href="https://doi.org/10.1007/s10038-003-0107-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14661080">Cao et al. (2004)</a> identified compound heterozygosity for 2 mutations in the ERCC8 gene: a G-to-T transversion, resulting in a glu13-to-ter (E13X) substitution, and A205P (<a href="#0005">609412.0005</a>). The patient was an 11-year-old girl with photophobia, dwarfism, mental retardation, cataracts, retinopathy, and optic atrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14661080" 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> rs121434325 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434325;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/rs121434325?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=rs121434325" 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=rs121434325" 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=RCV000001787 OR RCV000059647" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001787, RCV000059647" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001787...</a>
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<p>In a cell line from a patient with Cockayne syndrome A (<a href="/entry/216400">216400</a>), <a href="#12" class="mim-tip-reference" title="Ridley, A. J., Colley, J., Wynford-Thomas, D., Jones, C. J. <strong>Characterisation of novel mutations in Cockayne syndrome type A and xeroderma pigmentosum group C subjects.</strong> J. Hum. Genet. 50: 151-154, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15744458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15744458</a>] [<a href="https://doi.org/10.1007/s10038-004-0228-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15744458">Ridley et al. (2005)</a> identified compound heterozygosity for 2 mutations in the ERCC8 gene: a 479C-T transition, resulting in an ala160-to-val (A160V) substitution between the second and third WD40 repeats, and E13X (<a href="#0003">609412.0003</a>). No CSA protein was detected in the cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15744458" 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 COCKAYNE SYNDROME A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121434326 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434326;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/rs121434326?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=rs121434326" 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=rs121434326" 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=RCV000001788 OR RCV000059650 OR RCV005031380" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001788, RCV000059650, RCV005031380" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001788...</a>
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<p>In a cell line from a patient with Cockayne syndrome A (<a href="/entry/216400">216400</a>), <a href="#3" class="mim-tip-reference" title="Cao, H., Williams, C., Carter, M., Hegele, R. A. <strong>CKN1 (MIM 216400): mutations in Cockayne syndrome type A and a new common polymorphism.</strong> J. Hum. Genet. 49: 61-63, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14661080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14661080</a>] [<a href="https://doi.org/10.1007/s10038-003-0107-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14661080">Cao et al. (2004)</a> identified compound heterozygosity for 2 mutations in the ERCC8 gene: a 649G-C transversion, resulting in an ala205-to-pro (A205P) substitution, and E13X (<a href="#0003">609412.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14661080" 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">rs281875221 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281875221;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=rs281875221" 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=rs281875221" 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=RCV000024268 OR RCV000059645" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000024268, RCV000059645" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000024268...</a>
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<p>In a 15-year-old French girl with UV-sensitive syndrome-2 (UVSS2; <a href="/entry/614621">614621</a>), <a href="#10" class="mim-tip-reference" title="Nardo, T., Oneda, R., Spivak, G., Vaz, B., Mortier, L., Thomas, P., Orioli, D., Laugel, V., Stary, A., Hanawalt, P. C., Sarasin, A., Stefanini, M. <strong>A UV-sensitive syndrome patient with a specific CSA mutation reveals separable roles for CSA in response to UV and oxidative DNA damage.</strong> Proc. Nat. Acad. Sci. 106: 6209-6214, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19329487/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19329487</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19329487[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.0902113106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19329487">Nardo et al. (2009)</a> identified a homozygous 1083G-T transversion in the ERCC8 gene, resulting in a trp361-to-cys (W361C) substitution within the last putative WD domain. Her unaffected mother was heterozygous for the mutation. Patient-derived fibroblasts showed a reduced recovery of RNA synthesis after UV irradiation and a defective capacity to repair UV-induced damage on the transcribed strand of active genes, indicating a defect in transcription-coupled nucleotide excision repair (TC-NER). However, there was no hypersensitivity to reactive oxygen species, and UV-induced DNA repair synthesis and global genome NER (GG-NER) were normal. Transfection of the construct expressing the mutant protein into normal cells caused a defect in RNA synthesis after UV irradiation. The patient presented at age 4 months with sun sensitivity manifest as easy sun burning and erythema. She had numerous freckles on her face and exposed areas of the neck, but no history or evidence of cutaneous tumors. Psychomotor development was normal. <a href="#10" class="mim-tip-reference" title="Nardo, T., Oneda, R., Spivak, G., Vaz, B., Mortier, L., Thomas, P., Orioli, D., Laugel, V., Stary, A., Hanawalt, P. C., Sarasin, A., Stefanini, M. <strong>A UV-sensitive syndrome patient with a specific CSA mutation reveals separable roles for CSA in response to UV and oxidative DNA damage.</strong> Proc. Nat. Acad. Sci. 106: 6209-6214, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19329487/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19329487</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19329487[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.0902113106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19329487">Nardo et al. (2009)</a> hypothesized that the mild phenotype in this patient was due to the lack of cellular sensitivity to oxidative stress. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19329487" 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>See Also:</strong>
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<a href="#Cleaver1999" class="mim-tip-reference" title="Cleaver, J. E., Thompson, L. H., Richardson, A. S., States, J. C. <strong>A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy.</strong> Hum. Mutat. 14: 9-22, 1999.">Cleaver et al. (1999)</a>
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<strong>REFERENCES</strong>
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Bertola, D. R., Cao, H., Albano, L. M. J., Oliveira, D. P., Kok, F., Marques-Dias, M. J., Kim, C. A., Hegele, R. A.
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<strong>Cockayne syndrome type A: novel mutations in eight typical patients.</strong>
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J. Hum. Genet. 51: 701-705, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16865293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16865293</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16865293" 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/s10038-006-0011-7" target="_blank">Full Text</a>]
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Bregman, D. B., Halaban, R., van Gool, A. J., Henning, K. A., Friedberg, E. C., Warren, S. L.
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<strong>UV-induced ubiquitination of RNA polymerase II: a novel modification deficient in Cockayne syndrome cells.</strong>
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Proc. Nat. Acad. Sci. 93: 11586-11590, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8876179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8876179</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8876179" 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.93.21.11586" target="_blank">Full Text</a>]
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Cao, H., Williams, C., Carter, M., Hegele, R. A.
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<strong>CKN1 (MIM 216400): mutations in Cockayne syndrome type A and a new common polymorphism.</strong>
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J. Hum. Genet. 49: 61-63, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14661080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14661080</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14661080" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Cleaver, J. E., Thompson, L. H., Richardson, A. S., States, J. C.
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<strong>A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy.</strong>
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Hum. Mutat. 14: 9-22, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10447254/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10447254</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10447254" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)14:1<9::AID-HUMU2>3.0.CO;2-6" target="_blank">Full Text</a>]
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Fousteri, M., Vermeulen, W., van Zeeland, A. A., Mullenders, L. H. F.
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<strong>Cockayne syndrome A and B proteins differentially regulate recruitment of chromatin remodeling and repair factors to stalled RNA polymerase II in vivo.</strong>
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Molec. Cell 23: 471-482, 2006. Note: Retraction: Molec. Cell 81: 5112 only, 2021.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16916636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16916636</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16916636" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Groisman, R., Polanowska, J., Kuraoka, I., Sawada, J., Saijo, M., Drapkin, R., Kisselev, A. F., Tanaka, K., Nakatani, Y.
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<strong>The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage.</strong>
|
|
Cell 113: 357-367, 2003.
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|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12732143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12732143</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12732143" 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/s0092-8674(03)00316-7" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="7" class="mim-anchor"></a>
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<a id="Henning1995" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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|
Henning, K. A., Li, L., Iyer, N., McDaniel, L. D., Reagan, M. S., Legerski, R., Schultz, R. A., Stefanini, M., Lehmann, A. R., Mayne, L. V., Friedberg, E. C.
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<strong>The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CSB protein and a subunit of RNA polymerase II TFIIH.</strong>
|
|
Cell 82: 555-564, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7664335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7664335</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7664335" 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/10.1016/0092-8674(95)90028-4" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Khayat2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Khayat, M., Hardouf, H., Zlotogora, J., Shalev, S. A.
|
|
<strong>High carriers frequency of an apparently ancient founder mutation p.Tyr322X in the ERCC8 gene responsible for Cockayne syndrome among Christian Arabs in northern Israel.</strong>
|
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Am. J. Med. Genet. 152A: 3091-3094, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21108394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21108394</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21108394" 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.33746" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="McDaniel1997" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
|
McDaniel, L. D., Legerski, R., Lehmann, A. R., Friedberg, E. C., Schultz, R. A.
|
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<strong>Confirmation of homozygosity for a single nucleotide substitution mutation in a Cockayne syndrome patient using monoallelic mutation analysis in somatic cell hybrids.</strong>
|
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Hum. Mutat. 10: 317-321, 1997.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9338586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9338586</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9338586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/(SICI)1098-1004(1997)10:4<317::AID-HUMU8>3.0.CO;2-D" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Nardo2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Nardo, T., Oneda, R., Spivak, G., Vaz, B., Mortier, L., Thomas, P., Orioli, D., Laugel, V., Stary, A., Hanawalt, P. C., Sarasin, A., Stefanini, M.
|
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<strong>A UV-sensitive syndrome patient with a specific CSA mutation reveals separable roles for CSA in response to UV and oxidative DNA damage.</strong>
|
|
Proc. Nat. Acad. Sci. 106: 6209-6214, 2009.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19329487/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19329487</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19329487[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=19329487" 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.0902113106" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Neer1994" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
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Neer, E. J., Schmidt, C. J., Nambudripad, R., Smith, T. F.
|
|
<strong>The ancient regulatory-protein family of WD-repeat proteins.</strong>
|
|
Nature 371: 297-300, 1994. Note: Erratum: Nature 371: 812 only, 1994.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8090199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8090199</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8090199" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/371297a0" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Ridley2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ridley, A. J., Colley, J., Wynford-Thomas, D., Jones, C. J.
|
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<strong>Characterisation of novel mutations in Cockayne syndrome type A and xeroderma pigmentosum group C subjects.</strong>
|
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J. Hum. Genet. 50: 151-154, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15744458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15744458</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15744458" 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/s10038-004-0228-2" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Troelstra1992" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Troelstra, C., van Gool, A., de Wit, J., Vermeulen, W., Bootsma, D., Hoeijmakers, J. H. J.
|
|
<strong>ERCC6, a member of a subfamily of putative helicases, is involved in Cockayne's syndrome and preferential repair of active genes.</strong>
|
|
Cell 71: 939-953, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1339317/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1339317</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1339317" 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/10.1016/0092-8674(92)90390-x" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="van Gool1997" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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van Gool, A. J., van der Horst, G. T. J., Citterio, E., Hoeijmakers, J. H. J.
|
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<strong>Cockayne syndrome: defective repair of transcription?</strong>
|
|
EMBO J. 16: 4155-4162, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9250659/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9250659</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9250659" 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/emboj/16.14.4155" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 5/15/2012
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 1/26/2012<br>Patricia A. Hartz - updated : 10/31/2006<br>Marla J. F. O'Neill - updated : 10/24/2006<br>Patricia A. Hartz - updated : 7/6/2006
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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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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Cassandra L. Kniffin : 6/13/2005
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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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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carol : 01/17/2023
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</span>
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</div>
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</div>
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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 : 09/16/2022<br>carol : 01/27/2022<br>mcolton : 06/03/2015<br>ckniffin : 6/20/2013<br>terry : 3/14/2013<br>carol : 5/16/2012<br>ckniffin : 5/15/2012<br>carol : 5/14/2012<br>terry : 1/26/2012<br>wwang : 3/15/2007<br>carol : 10/31/2006<br>wwang : 10/25/2006<br>terry : 10/24/2006<br>mgross : 7/7/2006<br>terry : 7/6/2006<br>joanna : 8/9/2005<br>carol : 6/15/2005<br>ckniffin : 6/14/2005
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
|
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<strong>*</strong> 609412
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</span>
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</h3>
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</div>
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<div>
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<h3>
|
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<span class="mim-font">
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ERCC EXCISION REPAIR 8, CSA UBIQUITIN LIGASE COMPLEX SUBUNIT; ERCC8
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
EXCISION REPAIR CROSS-COMPLEMENTING, GROUP 8<br />
|
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CSA GENE<br />
|
|
CKN1 GENE
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: ERCC8</em></strong>
|
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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|
<strong>SNOMEDCT:</strong> 890433006;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: 5q12.1
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 5:60,866,454-60,945,070 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
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</p>
|
|
</div>
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<div>
|
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<br />
|
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
5q12.1
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Cockayne syndrome, type A
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
216400
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
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</td>
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</tr>
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
UV-sensitive syndrome 2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
614621
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<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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</tbody>
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</table>
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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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<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 ERCC8 gene is part of the nucleotide excision repair (NER) pathway, a complex system that eliminates a broad spectrum of structural DNA lesions, including ultraviolet (UV)-induced cyclobutane pyrimidine dimers, bulky chemical adducts, and DNA cross-links. One of the NER pathways preferentially repairs lesions on the transcribed strand of active genes; this process occurs more rapidly than repairs on nontranscribed strands that are part of overall genome repair (Troelstra et al., 1992). </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>Henning et al. (1995) cloned the human CKN1 gene, which they called CSA, by functional complementation of cells derived from patients with Cockayne syndrome A (CSA; 216400). They found that the CSA cDNA uniquely and specifically corrected UV sensitivity in CSA cells. The predicted 396-amino acid protein has a calculated molecular mass of approximately 44 kD and contains a WD repeat (WD40 repeat) domain as reviewed by Neer et al. (1994). In vitro translated CSA protein specifically interacted with the CSB (ERCC6; 609413) protein and p44 protein (GTF2H2; 601748), a subunit of the RNA polymerase II basal transcription factor TFIIH (see also 189972). These observations, coupled with the observation that the amino acid sequence of the predicted CSB polypeptide is homologous with a component of the yeast Swi/Snf transcriptional activation complex, suggested that Cockayne syndrome cells are defective in RNA polymerase II transcription. </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>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By Southern blot hybridization in human/rodent hybrid cell DNA, Henning et al. (1995) mapped the CSA gene to chromosome 5. </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>Damage to actively transcribed DNA is preferentially repaired by the transcription-coupled repair (TCR) system, which requires RNA polymerase II (pol II). Bregman et al. (1996) demonstrated that a fraction of the large subunit of pol II (POL2R; 180660) was ubiquitinated after exposing cells to UV-radiation or cisplatin but not several other DNA-damaging agents. This novel covalent modification of POL2R occurred within 15 minutes of exposing cells to UV-radiation and persisted for about 8 to 12 hours. Ubiquitinated POL2R was also phosphorylated on the C-terminal domain. UV-induced ubiquitination of POL2R was deficient in fibroblasts from persons with either Cockayne syndrome A or B (133540). In both of these disorders, transcription-coupled repair is disrupted. UV-induced ubiquitination of POL2R could be restored by introducing cDNA constructs encoding the CSA or CSB genes, respectively, into CSA or CSB fibroblasts. These results suggested that ubiquitination of POL2R plays a role in the recognition and/or repair of damage to actively transcribed genes. Alternatively, these findings may reflect a role played by the CSA and CSB gene products in transcription, a possibility that had been suggested on other grounds. </p><p>Van Gool et al. (1997) noted that there is evidence that basic metabolic processes within the cell are intimately linked and influenced by one another. One such link is the close interplay between nucleotide excision DNA repair and transcription, as illustrated both by the preferential repair of the transcribed strand of active genes (TCR) and by the distinct dual involvement of proteins in both processes. In E. coli, 1 protein, the transcription repair-coupling factor, accomplishes the dual function. On the basis of experimental observations, van Gool et al. (1997) suggested that the situation in eukaryotes is more complex, involving dual functionality of multiple proteins. They suggested that Cockayne syndrome may represent a defect in TCR. </p><p>By immunoprecipitation analysis of HeLa cells, Groisman et al. (2003) identified DDB2 (600811) and CSA as components of similar but distinct protein complexes. Both DDB2 and CSA interacted with DDB1 (600045), a component of both complexes. Cullin-4A (CUL4A; 603137), ROC1 (RBX1; 603814), and all the subunits of the COP9 signalosome (e.g., COPS2; 604508) were also present in both complexes. Following UV irradiation, the DDB2 complex bound tightly to chromatin in a UV-dependent manner and initiated global genome repair, whereas the CSA complex bound to RNA polymerase II and initiated TCR. The COP9 signalosome in each complex differentially regulated cullin-based ubiquitin ligase activity in response to UV irradiation. </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>Cockayne Syndrome A</em></strong></p><p>
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|
Henning et al. (1995) identified mutations in the ERCC8 gene in CSA cDNAs of all CSA cell lines examined, including an identical mutation in 2 CSA sibs (609412.0001). </p><p>In a cell line from an 11-year-old girl with CSA, Cao et al. (2004) identified compound heterozygosity for a nonsense mutation (E13X; 609412.0003) and a missense mutation (A205P; 609412.0005) in the ERCC8 gene. </p><p>In a cell line from a patient with CSA, Ridley et al. (2005) identified compound heterozygosity for an E13X mutation and a novel missense mutation (A160V; 609412.0004) in the ERCC8 gene. </p><p>Bertola et al. (2006) analyzed the ERCC8 gene in 8 patients from 6 Brazilian families with typical CSA and identified homozygosity or compound heterozygosity for ERCC8 mutations in all of them. The authors stated that there was no obvious genotype/phenotype correlation across the mutation spectrum. </p><p><strong><em>UV-Sensitive Syndrome 2</em></strong></p><p>
|
|
In a 15-year-old French girl with UV-sensitive syndrome-2 (UVSS2; 614621), Nardo et al. (2009) identified a homozygous mutation in the ERCC8 gene (W361C; 609412.0006). She had sun sensitivity and freckling, but no other abnormalities. Patient-derived fibroblasts showed a reduced recovery of RNA synthesis after UV irradiation and a defective capacity to repair UV-induced damage on the transcribed strand of active genes, indicating a defect in transcription-coupled nucleotide excision repair (TC-NER). However, there was no hypersensitivity to reactive oxygen species, and UV-induced DNA repair synthesis and global genome NER (GG-NER) were normal. Nardo et al. (2009) hypothesized that the mild phenotype in this patient was due to the lack of cellular sensitivity to oxidative stress. </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>History</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>The article by Fousteri et al. (2006) regarding the function of CSB and CSA in TCR complex formation was retracted because an investigation at the Leiden University Medical Center concluded that 'unacceptable data manipulation' by one of the authors 'led to breaches of scientific integrity, making these results unreliable.' </p>
|
|
</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
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</span>
|
|
<strong>6 Selected Examples):</strong>
|
|
</span>
|
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</h4>
|
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<div>
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<p />
|
|
</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 COCKAYNE SYNDROME A</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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|
|
|
ERCC8, 279-BP DEL, 81-BP DEL
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<br />
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ClinVar: RCV000001784
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|
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|
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs, born of consanguineous parents, with Cockayne syndrome A (216400), Henning et al. (1995) identified 2 deletions in the ERCC8 gene. One deletion removed 279 bp from the CKN1 coding region, starting at nucleotide 880 of their sequence and ending at nucleotide 1158. A second deletion of 81 bp in the CKN1 region started at nucleotide position 1078 and also ended at nucleotide position 1158. The fact that the deletions identified in both cDNAs from both sibs ended at the identical nucleotide positions strongly suggested to the authors that this nucleotide marks an exon/intron junction and the truncated cDNAs represent abnormally spliced products missing either 1 (81 bp) or 2 (279 bp) upstream exons. These abnormal splice products presumably derived from a homozygous mutation in a splice donor site. Neither deletion created a frameshift. Hence, the 2 abnormal transcripts potentially encode internally deleted proteins with predicted sizes of 303 and 369 amino acids. </p>
|
|
</span>
|
|
</div>
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<div>
|
|
<br />
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|
</div>
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</div>
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 COCKAYNE SYNDROME A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ERCC8, TYR322TER
|
|
|
|
|
|
<br />
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|
|
SNP: rs121434323,
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|
|
|
|
|
gnomAD: rs121434323,
|
|
|
|
|
|
ClinVar: RCV000001785, RCV001388976, RCV003330380
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a cell line derived from a patient with Cockayne syndrome A (216400), Henning et al. (1995) identified a C-to-A transversion in the ERCC8 gene, resulting in a tyr322-to-ter (Y322X) substitution. </p><p>McDaniel et al. (1997) demonstrated that the Y322X mutation was present in homozygous state, using a strategy with general applicability. Somatic cell hybrids were established by fusing patient cells with mouse A9 cells. Screening with chromosome 5-specific polymorphic markers facilitated identification of hybrid clones bearing only 1 of the distinct CSA alleles. Sequencing a portion of the human CSA gene in a subset of these hybrids permitted monoallelic mutation analysis and confirmed the presence of the Y322X mutation in both alleles. </p><p>Khayat et al. (2010) analyzed the Y322X mutation in the Arab Christian population of northern Israel and found a carrier frequency of 6.79. Haplotype analysis as well as the high carrier frequency suggested that Y322X is an ancient founder mutation that may have originated in the Christian Lebanese community. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 COCKAYNE SYNDROME A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
ERCC8, GLU13TER
|
|
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|
|
|
<br />
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|
|
|
SNP: rs121434324,
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|
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|
|
|
gnomAD: rs121434324,
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|
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|
|
|
ClinVar: RCV000001786, RCV001064361, RCV001280547, RCV002490294
|
|
|
|
|
|
</span>
|
|
</div>
|
|
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|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a cell line from a patient with Cockayne syndrome A (216400), Cao et al. (2004) identified compound heterozygosity for 2 mutations in the ERCC8 gene: a G-to-T transversion, resulting in a glu13-to-ter (E13X) substitution, and A205P (609412.0005). The patient was an 11-year-old girl with photophobia, dwarfism, mental retardation, cataracts, retinopathy, and optic atrophy. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
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|
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</div>
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|
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<div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 COCKAYNE SYNDROME A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
ERCC8, ALA160VAL
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|
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<br />
|
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|
|
SNP: rs121434325,
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|
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|
|
gnomAD: rs121434325,
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|
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|
|
ClinVar: RCV000001787, RCV000059647
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a cell line from a patient with Cockayne syndrome A (216400), Ridley et al. (2005) identified compound heterozygosity for 2 mutations in the ERCC8 gene: a 479C-T transition, resulting in an ala160-to-val (A160V) substitution between the second and third WD40 repeats, and E13X (609412.0003). No CSA protein was detected in the cells. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
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<br />
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|
</div>
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|
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</div>
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|
<div>
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 COCKAYNE SYNDROME A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
|
|
|
|
ERCC8, ALA205PRO
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|
|
|
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<br />
|
|
|
|
SNP: rs121434326,
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|
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|
|
|
gnomAD: rs121434326,
|
|
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|
|
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ClinVar: RCV000001788, RCV000059650, RCV005031380
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a cell line from a patient with Cockayne syndrome A (216400), Cao et al. (2004) identified compound heterozygosity for 2 mutations in the ERCC8 gene: a 649G-C transversion, resulting in an ala205-to-pro (A205P) substitution, and E13X (609412.0003). </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>.0006 UV-SENSITIVE SYNDROME 2</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
ERCC8, TRP361CYS
|
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|
|
|
|
<br />
|
|
|
|
SNP: rs281875221,
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|
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|
|
ClinVar: RCV000024268, RCV000059645
|
|
|
|
|
|
</span>
|
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</div>
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 15-year-old French girl with UV-sensitive syndrome-2 (UVSS2; 614621), Nardo et al. (2009) identified a homozygous 1083G-T transversion in the ERCC8 gene, resulting in a trp361-to-cys (W361C) substitution within the last putative WD domain. Her unaffected mother was heterozygous for the mutation. Patient-derived fibroblasts showed a reduced recovery of RNA synthesis after UV irradiation and a defective capacity to repair UV-induced damage on the transcribed strand of active genes, indicating a defect in transcription-coupled nucleotide excision repair (TC-NER). However, there was no hypersensitivity to reactive oxygen species, and UV-induced DNA repair synthesis and global genome NER (GG-NER) were normal. Transfection of the construct expressing the mutant protein into normal cells caused a defect in RNA synthesis after UV irradiation. The patient presented at age 4 months with sun sensitivity manifest as easy sun burning and erythema. She had numerous freckles on her face and exposed areas of the neck, but no history or evidence of cutaneous tumors. Psychomotor development was normal. Nardo et al. (2009) hypothesized that the mild phenotype in this patient was due to the lack of cellular sensitivity to oxidative stress. </p>
|
|
</span>
|
|
</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Cleaver et al. (1999)
|
|
</span>
|
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<div>
|
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<br />
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</div>
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
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</h4>
|
|
<div>
|
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<p />
|
|
</div>
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<div>
|
|
<ol>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Bertola, D. R., Cao, H., Albano, L. M. J., Oliveira, D. P., Kok, F., Marques-Dias, M. J., Kim, C. A., Hegele, R. A.
|
|
<strong>Cockayne syndrome type A: novel mutations in eight typical patients.</strong>
|
|
J. Hum. Genet. 51: 701-705, 2006.
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|
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|
|
[PubMed: 16865293]
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|
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[Full Text: https://doi.org/10.1007/s10038-006-0011-7]
|
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Bregman, D. B., Halaban, R., van Gool, A. J., Henning, K. A., Friedberg, E. C., Warren, S. L.
|
|
<strong>UV-induced ubiquitination of RNA polymerase II: a novel modification deficient in Cockayne syndrome cells.</strong>
|
|
Proc. Nat. Acad. Sci. 93: 11586-11590, 1996.
|
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|
|
[PubMed: 8876179]
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[Full Text: https://doi.org/10.1073/pnas.93.21.11586]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Cao, H., Williams, C., Carter, M., Hegele, R. A.
|
|
<strong>CKN1 (MIM 216400): mutations in Cockayne syndrome type A and a new common polymorphism.</strong>
|
|
J. Hum. Genet. 49: 61-63, 2004.
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|
|
[PubMed: 14661080]
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