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- *610060 - POLYMERASE I, RNA, SUBUNIT C; POLR1C
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- OMIM
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<p>
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<span class="h4">*610060</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="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</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/610060">Table View</a>
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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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<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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<h4 class="panel-title">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000171453;t=ENST00000642195" 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=9533" 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=610060" 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 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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<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=ENSG00000171453;t=ENST00000642195" 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_001318876,NM_001363658,NM_203290" 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_203290" 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=610060" 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=09661&isoform_id=09661_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/POLR1C" 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/2266929,3335138,3914807,14198113,14250788,42560246,119624609,119624610,119624613,194374275,444738443,974141108,1391723933" 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/O15160" 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=9533" 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=ENSG00000171453;t=ENST00000642195" 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=POLR1C" 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=POLR1C" 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+9533" 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/POLR1C" 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:9533" 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/9533" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr6&hgg_gene=ENST00000642195.1&hgg_start=43517089&hgg_end=43562407&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:20194" 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/polr1c" 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=610060[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 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=610060[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/POLR1C/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/ENSG00000171453" 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=POLR1C" 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=POLR1C" 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=POLR1C" 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=POLR1C&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/PA134882004" 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:20194" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0031657.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:103288" 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/POLR1C#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:103288" 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/9533/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=9533" 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=WBGene00019275;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-040426-1495" 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:9533" 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=POLR1C&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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610060
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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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POLYMERASE I, RNA, SUBUNIT C; POLR1C
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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RPA39<br />
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RPA40<br />
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RPAC1<br />
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RPA5
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=POLR1C" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">POLR1C</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/6/528?start=-3&limit=10&highlight=528">6p21.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr6:43517089-43562407&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">6:43,517,089-43,562,407</a> </span>
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
|
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<span class="hidden-sm hidden-xs pull-right">
|
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<a href="/clinicalSynopsis/table?mimNumber=616494,248390" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
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</a>
|
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</span>
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
|
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="2">
|
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<span class="mim-font">
|
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<a href="/geneMap/6/528?start=-3&limit=10&highlight=528">
|
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6p21.1
|
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</a>
|
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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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Leukodystrophy, hypomyelinating, 11
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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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<a href="/entry/616494"> 616494 </a>
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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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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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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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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<tr>
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<td>
|
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<span class="mim-font">
|
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Treacher Collins syndrome 3
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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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<a href="/entry/248390"> 248390 </a>
|
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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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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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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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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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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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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
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<p>The POLR1C gene encodes a subunit that is shared by both RNA polymerase I (POLR1) and RNA polymerase III (POLR3) (summary by <a href="#6" class="mim-tip-reference" title="Thiffault, I., Wolf, N. I., Forget, D., Guerrero, K., Tran, L. T., Choquet, K., Lavallee-Adam, M., Poitras, C., Brais, B., Yoon, G., Sztriha, L., Webster, R. I., and 15 others. <strong>Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III.</strong> Nature Commun. 6: 7623, 2015. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26151409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26151409</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26151409[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/10.1038/ncomms8623" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26151409">Thiffault et al., 2015</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26151409" 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 sequencing cDNAs obtained from umbilical cord blood CD34 (<a href="/entry/142230">142230</a>)-positive hematopoietic stem/progenitor cells, <a href="#3" class="mim-tip-reference" title="Mao, M., Fu, G., Wu, J.-S., Zhang, Q.-H., Zhou, J., Kan, L.-X., Huang, Q.-H., He, K.-L., Gu, B.-W., Han, Z.-G., Shen, Y., Gu, J., Yu, Y.-P., Xu, S.-H., Wang, Y.-X., Chen, S.-J., Chen, Z. <strong>Identification of genes expressed in human CD34+ hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning.</strong> Proc. Nat. Acad. Sci. 95: 8175-8180, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9653160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9653160</a>] [<a href="https://doi.org/10.1073/pnas.95.14.8175" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9653160">Mao et al. (1998)</a> cloned POLR1C, which they called RPA40. The deduced protein contains 342 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9653160" 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 sequencing proteins contained within RNA polymerase III complexes purified from HeLa cells, followed by database analysis, <a href="#2" class="mim-tip-reference" title="Hu, P., Wu, S., Sun, Y., Yuan, C.-C., Kobayashi, R., Myers, M. P., Hernandez, N. <strong>Characterization of human RNA polymerase III identifies orthologues for Saccharomyces cerevisiae RNA polymerase III subunits.</strong> Molec. Cell. Biol. 22: 8044-8055, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12391170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12391170</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12391170[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/10.1128/MCB.22.22.8044-8055.2002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12391170">Hu et al. (2002)</a> identified POLR1C, which they called RPAC1. The deduced 342-amino acid protein has a calculated molecular mass of 38.6 kD and shares 47% amino acid identity with its yeast homolog, AC40. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12391170" 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="#5" class="mim-tip-reference" title="Stumpf, A. M. <strong>Personal Communication.</strong> Baltimore, Md. 02/21/2022."None>Stumpf (2022)</a> mapped the POLR1C gene to chromosome 6p21.1 based on an alignment of the POLR1C sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=BC008863" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">BC008863</a>) with the genomic sequence (GRCh38).</p>
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<p><strong><em>Treacher Collins Syndrome 3</em></strong></p><p>
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<a href="#1" class="mim-tip-reference" title="Dauwerse, J. G., Dixon, J., Seland, S., Ruivenkamp, C. A. L., van Haeringen, A., Hoefsloot, L. H., Peters, D. J. M., Clement-de Boers, A., Daumer-Haas, C., Maiwald, R., Zweier, C., Kerr, B., Cobo, A. M., Toral, J. F., Hoogeboom, A. J. M., Lohmann, D. R., Hehr, U., Dixon, M. J., Breuning, M. H., Wieczorek, D. <strong>Mutations in gene encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome.</strong> Nature Genet. 43: 20-22, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21131976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21131976</a>] [<a href="https://doi.org/10.1038/ng.724" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21131976">Dauwerse et al. (2011)</a> analyzed the POLR1C gene in 252 individuals with Treacher Collins syndrome (TCS3; <a href="/entry/248390">248390</a>) and identified 3 patients with compound heterozygous mutations (<a href="#0001">610060.0001</a>-<a href="#0005">610060.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21131976" 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>Hypomyelinating Leukodystrophy 11</em></strong></p><p>
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In 8 patients with hypomyelinating leukodystrophy-11 (HLD11; <a href="/entry/616494">616494</a>) who were negative for mutations in the POLR3A (<a href="/entry/614258">614258</a>) and POLR3B (<a href="/entry/614366">614366</a>) genes, <a href="#6" class="mim-tip-reference" title="Thiffault, I., Wolf, N. I., Forget, D., Guerrero, K., Tran, L. T., Choquet, K., Lavallee-Adam, M., Poitras, C., Brais, B., Yoon, G., Sztriha, L., Webster, R. I., and 15 others. <strong>Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III.</strong> Nature Commun. 6: 7623, 2015. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26151409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26151409</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26151409[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/10.1038/ncomms8623" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26151409">Thiffault et al. (2015)</a> identified 13 homozygous or compound heterozygous mutations in the POLR1C gene (see, e.g., <a href="#0006">610060.0006</a>-<a href="#0011">610060.0011</a>). Mutations in the first 3 patients were found by whole-exome sequencing and segregated with the disorder in the families. Subsequent mutations in 5 patients were found by direct sequencing of the POLR1C gene in 16 individuals with a similar phenotype who were negative for POLR3A and POLR3B mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26151409" 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 in vitro functional expression assays in HeLa cells, <a href="#6" class="mim-tip-reference" title="Thiffault, I., Wolf, N. I., Forget, D., Guerrero, K., Tran, L. T., Choquet, K., Lavallee-Adam, M., Poitras, C., Brais, B., Yoon, G., Sztriha, L., Webster, R. I., and 15 others. <strong>Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III.</strong> Nature Commun. 6: 7623, 2015. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26151409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26151409</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26151409[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/10.1038/ncomms8623" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26151409">Thiffault et al. (2015)</a> found that the POLR1C R279Q mutation (<a href="#0001">610060.0001</a>) associated with Treacher Collins syndrome did not affect the assembly of either RNA polymerase I or III. However, the R279Q mutation impaired targeting of the protein to the nucleolus, the site for RNA polymerase I gene transcription. In contrast, 2 missense mutations associated with HLD11 (N74S; <a href="#0006">610060.0006</a> and N32I; <a href="#0007">610060.0007</a>) specifically interfered with assembly and nuclear import of RNA polymerase III, but not RNA polymerase I. The findings provided a pathophysiologic mechanism for the different clinical conditions resulting from different mutations in the same gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26151409" 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> rs191582628 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs191582628;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/rs191582628?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=rs191582628" 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=rs191582628" 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=RCV000023796 OR RCV000513700 OR RCV000788034 OR RCV002281718 OR RCV002504821 OR RCV002513205" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023796, RCV000513700, RCV000788034, RCV002281718, RCV002504821, RCV002513205" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023796...</a>
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<p>In a sister and brother and an unrelated male patient with Treacher Collins syndrome-3 (TCS3; <a href="/entry/248390">248390</a>), <a href="#1" class="mim-tip-reference" title="Dauwerse, J. G., Dixon, J., Seland, S., Ruivenkamp, C. A. L., van Haeringen, A., Hoefsloot, L. H., Peters, D. J. M., Clement-de Boers, A., Daumer-Haas, C., Maiwald, R., Zweier, C., Kerr, B., Cobo, A. M., Toral, J. F., Hoogeboom, A. J. M., Lohmann, D. R., Hehr, U., Dixon, M. J., Breuning, M. H., Wieczorek, D. <strong>Mutations in gene encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome.</strong> Nature Genet. 43: 20-22, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21131976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21131976</a>] [<a href="https://doi.org/10.1038/ng.724" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21131976">Dauwerse et al. (2011)</a> identified compound heterozygosity for an 836G-A transition in exon 8 of the POLR1C gene, resulting in an arg279-to-gln (R279Q) substitution at a highly conserved residue in the RNA polymerase dimerization domain of POLR1C, and another mutation in POLR1C. The second mutation in the sister and her more severely affected brother, who had previously been studied by <a href="#4" class="mim-tip-reference" title="Splendore, A., Silva, E. O., Alonso, L. G., Richieri-Costa, A., Alonso, N., Rosa, A., Carakushanky, G., Cavalcanti, D. P., Brunoni, D., Passos-Bueno, M. R. <strong>High mutation detection rate in TCOF1 among Treacher Collins syndrome patients reveals clustering of mutations and 16 novel pathogenic changes.</strong> Hum. Mutat. 16: 315-322, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11013442/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11013442</a>] [<a href="https://doi.org/10.1002/1098-1004(200010)16:4<315::AID-HUMU4>3.0.CO;2-H" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11013442">Splendore et al. (2000)</a>, was a 4-bp deletion in intron 8 (<a href="#0002">610060.0002</a>) at the splice donor site (922+3_922+6del), predicted to result in skipping of exon 8. The unrelated patient's second mutation was a 979A-T transversion in exon 9, resulting in a lys327-to-ter (K327X; <a href="#0003">610060.0003</a>) substitution. The unrelated patient's unaffected parents were each heterozygous for 1 of the mutations; the sibs' unaffected mother and her healthy sister were heterozygous for the R279Q mutation, but DNA from their deceased father was unavailable for study. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11013442+21131976" 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">rs1335699710 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1335699710;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=rs1335699710" 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=rs1335699710" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the 4-bp deletion in the POLR1C gene (922+3_922+6del) that was found in compound heterozygous state in sibs with Treacher Collins syndrome-3 (TCS3; <a href="/entry/248390">248390</a>) by <a href="#1" class="mim-tip-reference" title="Dauwerse, J. G., Dixon, J., Seland, S., Ruivenkamp, C. A. L., van Haeringen, A., Hoefsloot, L. H., Peters, D. J. M., Clement-de Boers, A., Daumer-Haas, C., Maiwald, R., Zweier, C., Kerr, B., Cobo, A. M., Toral, J. F., Hoogeboom, A. J. M., Lohmann, D. R., Hehr, U., Dixon, M. J., Breuning, M. H., Wieczorek, D. <strong>Mutations in gene encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome.</strong> Nature Genet. 43: 20-22, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21131976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21131976</a>] [<a href="https://doi.org/10.1038/ng.724" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21131976">Dauwerse et al. (2011)</a>, see <a href="#0001">610060.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21131976" 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> rs387907020 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907020;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/rs387907020?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=rs387907020" 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=rs387907020" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the lys327-to-ter (K327X) mutation in the POLR1C gene that was found in compound heterozygous state in a patient with Treacher Collins syndrome-3 (TCS3; <a href="/entry/248390">248390</a>) by <a href="#1" class="mim-tip-reference" title="Dauwerse, J. G., Dixon, J., Seland, S., Ruivenkamp, C. A. L., van Haeringen, A., Hoefsloot, L. H., Peters, D. J. M., Clement-de Boers, A., Daumer-Haas, C., Maiwald, R., Zweier, C., Kerr, B., Cobo, A. M., Toral, J. F., Hoogeboom, A. J. M., Lohmann, D. R., Hehr, U., Dixon, M. J., Breuning, M. H., Wieczorek, D. <strong>Mutations in gene encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome.</strong> Nature Genet. 43: 20-22, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21131976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21131976</a>] [<a href="https://doi.org/10.1038/ng.724" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21131976">Dauwerse et al. (2011)</a>, see <a href="#0001">610060.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21131976" 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">rs2127686639 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2127686639;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=rs2127686639" 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=rs2127686639" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a male patient with Treacher Collins syndrome-3 (TCS3; <a href="/entry/248390">248390</a>), <a href="#1" class="mim-tip-reference" title="Dauwerse, J. G., Dixon, J., Seland, S., Ruivenkamp, C. A. L., van Haeringen, A., Hoefsloot, L. H., Peters, D. J. M., Clement-de Boers, A., Daumer-Haas, C., Maiwald, R., Zweier, C., Kerr, B., Cobo, A. M., Toral, J. F., Hoogeboom, A. J. M., Lohmann, D. R., Hehr, U., Dixon, M. J., Breuning, M. H., Wieczorek, D. <strong>Mutations in gene encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome.</strong> Nature Genet. 43: 20-22, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21131976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21131976</a>] [<a href="https://doi.org/10.1038/ng.724" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21131976">Dauwerse et al. (2011)</a> identified compound heterozygosity for 2 mutations in the POLR1C gene: a 1-bp deletion (87delT) in exon 2, predicted to cause a frameshift and a premature termination codon, and an 835C-T transition in exon 8, resulting in an arg279-to-trp (R279W) substitution (<a href="#0005">610060.0005</a>). His unaffected parents were each heterozygous for 1 of the mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21131976" 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> rs141156009 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs141156009;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/rs141156009?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=rs141156009" 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=rs141156009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the arg279-to-trp (R279W) mutation in the POLR1C gene that was found in compound heterozygous state in a patient with Treacher Collins syndrome-3 (TCS3; <a href="/entry/248390">248390</a>) by <a href="#1" class="mim-tip-reference" title="Dauwerse, J. G., Dixon, J., Seland, S., Ruivenkamp, C. A. L., van Haeringen, A., Hoefsloot, L. H., Peters, D. J. M., Clement-de Boers, A., Daumer-Haas, C., Maiwald, R., Zweier, C., Kerr, B., Cobo, A. M., Toral, J. F., Hoogeboom, A. J. M., Lohmann, D. R., Hehr, U., Dixon, M. J., Breuning, M. H., Wieczorek, D. <strong>Mutations in gene encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome.</strong> Nature Genet. 43: 20-22, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21131976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21131976</a>] [<a href="https://doi.org/10.1038/ng.724" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21131976">Dauwerse et al. (2011)</a>, see <a href="#0004">610060.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21131976" 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> rs371802902 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs371802902;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/rs371802902?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=rs371802902" 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=rs371802902" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a Hungarian boy with hypomyelinating leukodystrophy-11 (HLD11; <a href="/entry/616494">616494</a>), <a href="#6" class="mim-tip-reference" title="Thiffault, I., Wolf, N. I., Forget, D., Guerrero, K., Tran, L. T., Choquet, K., Lavallee-Adam, M., Poitras, C., Brais, B., Yoon, G., Sztriha, L., Webster, R. I., and 15 others. <strong>Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III.</strong> Nature Commun. 6: 7623, 2015. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26151409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26151409</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26151409[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/10.1038/ncomms8623" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26151409">Thiffault et al. (2015)</a> identified a homozygous c.221A-G transition (c.221A-G, NM_203290) in exon 3 of the POLR1C gene, resulting in an asn74-to-ser (N74S) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was found at a very low frequency (less than 0.01%) in the Exome Sequencing Project and ExAC databases and was not found in the CEPH database. In vitro functional expression studies in HeLa cells showed that the mutant protein interacted less well with POLR3 than did wildtype, suggesting a selective defect in POLR3 assembly that did not affect POLR1 assembly. Immunofluorescence and immunoprecipitation studies showed cytoplasmic accumulation of mutated POLR1C subunits and reduced binding to POLR3-transcribed genes. In contrast, there was no difference between mutant and wildtype POLR1C in binding to POLR1-transcribed genes. The findings indicated that the N74S mutation specifically interfered with assembly, nuclear import, and chromatin association of POLR3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26151409" 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">rs796052124 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs796052124;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=rs796052124" 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=rs796052124" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a boy, born of consanguineous Libyan parents, with hypomyelinating leukodystrophy-11 (HLD11; <a href="/entry/616494">616494</a>), <a href="#6" class="mim-tip-reference" title="Thiffault, I., Wolf, N. I., Forget, D., Guerrero, K., Tran, L. T., Choquet, K., Lavallee-Adam, M., Poitras, C., Brais, B., Yoon, G., Sztriha, L., Webster, R. I., and 15 others. <strong>Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III.</strong> Nature Commun. 6: 7623, 2015. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26151409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26151409</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26151409[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/10.1038/ncomms8623" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26151409">Thiffault et al. (2015)</a> identified a homozygous c.95A-T transversion (c.95A-T, NM_203290) in exon 2 of the POLR1C gene, resulting in an asn32-to-ile (N32I) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the Exome Sequencing Project, ExAC, or CEPH databases. In vitro functional expression studies in HeLa cells showed that the mutant protein interacted less well with POLR3 than did wildtype, suggesting a selective defect in POLR3 assembly that did not affect POLR1 assembly. Immunofluorescence and immunoprecipitation studies showed cytoplasmic accumulation of mutated POLR1C subunits and reduced binding to POLR3-transcribed genes. In contrast, there was no difference between mutant and wildtype POLR1C in binding to POLR1-transcribed genes. The findings indicated that the N32I mutation specifically interfered with assembly, nuclear import, and chromatin association of POLR3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26151409" 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">rs796052125 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs796052125;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=rs796052125" 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=rs796052125" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a Chinese boy with hypomyelinating leukodystrophy-11 (HLD11; <a href="/entry/616494">616494</a>), <a href="#6" class="mim-tip-reference" title="Thiffault, I., Wolf, N. I., Forget, D., Guerrero, K., Tran, L. T., Choquet, K., Lavallee-Adam, M., Poitras, C., Brais, B., Yoon, G., Sztriha, L., Webster, R. I., and 15 others. <strong>Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III.</strong> Nature Commun. 6: 7623, 2015. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26151409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26151409</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26151409[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/10.1038/ncomms8623" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26151409">Thiffault et al. (2015)</a> identified compound heterozygous mutations in the POLR1C gene: a c.436T-C transition (c.436T-C, NM_203290) in exon 5, resulting in a cys146-to-arg (C146R) substitution at a highly conserved residue, and a 3-bp deletion in exon 8 (c.883_885delAAG; <a href="#0009">610060.0009</a>), resulting in an in-frame deletion of a conserved residue (Lys295del). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and were not found in the Exome Sequencing Project, ExAC, or CEPH databases. Functional studies of the variants were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26151409" 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">rs875989826 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs875989826;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=rs875989826" 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=rs875989826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the c.883_885delAAG (c.883_885delAAG, NM_203290) mutation in the POLR1C gene that was found in compound heterozygous state in a patient with hypomyelinating leukodystrophy-11 (HLD11; <a href="/entry/616494">616494</a>) by <a href="#6" class="mim-tip-reference" title="Thiffault, I., Wolf, N. I., Forget, D., Guerrero, K., Tran, L. T., Choquet, K., Lavallee-Adam, M., Poitras, C., Brais, B., Yoon, G., Sztriha, L., Webster, R. I., and 15 others. <strong>Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III.</strong> Nature Commun. 6: 7623, 2015. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26151409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26151409</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26151409[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/10.1038/ncomms8623" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26151409">Thiffault et al. (2015)</a>, see <a href="#0008">610060.0008</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26151409" 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">rs796052126 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs796052126;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=rs796052126" 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=rs796052126" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a girl with hypomyelinating leukodystrophy-11 (HLD11; <a href="/entry/616494">616494</a>), <a href="#6" class="mim-tip-reference" title="Thiffault, I., Wolf, N. I., Forget, D., Guerrero, K., Tran, L. T., Choquet, K., Lavallee-Adam, M., Poitras, C., Brais, B., Yoon, G., Sztriha, L., Webster, R. I., and 15 others. <strong>Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III.</strong> Nature Commun. 6: 7623, 2015. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26151409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26151409</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26151409[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/10.1038/ncomms8623" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26151409">Thiffault et al. (2015)</a> identified compound heterozygous mutations in the POLR1C gene: a c.77C-T transition (c.77C-T, NM_203290) in exon 2, resulting in a thr26-to-ile (T26I) substitution, and a c.326G-A transition in exon 4, resulting in an arg109-to-his (R109H; <a href="#0011">610060.0011</a>) substitution. Each unaffected parent was heterozygous for 1 of the mutations. Both mutations occurred at conserved residues. The variants were not found in the Exome Variant Server, Exome Aggregation Consortium, or CEPH databases, and functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26151409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0011 LEUKODYSTROPHY, HYPOMYELINATING, 11</strong>
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POLR1C, ARG109HIS
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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> rs796052127 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs796052127;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/rs796052127?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=rs796052127" 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=rs796052127" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000186589 OR RCV000853238 OR RCV003387792" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000186589, RCV000853238, RCV003387792" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000186589...</a>
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<span class="mim-text-font">
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<p>For discussion of the c.326G-A transition (c.326G-A, NM_203290) in the POLR1C gene, resulting in an arg109-to-his (R109H) substitution, that was found in compound heterozygous state in a patient with hypomyelinating leukodystrophy-11 (HLD11; <a href="/entry/616494">616494</a>) by <a href="#6" class="mim-tip-reference" title="Thiffault, I., Wolf, N. I., Forget, D., Guerrero, K., Tran, L. T., Choquet, K., Lavallee-Adam, M., Poitras, C., Brais, B., Yoon, G., Sztriha, L., Webster, R. I., and 15 others. <strong>Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III.</strong> Nature Commun. 6: 7623, 2015. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26151409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26151409</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26151409[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/10.1038/ncomms8623" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26151409">Thiffault et al. (2015)</a>, see <a href="#0010">610060.0010</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26151409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-font">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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</h4>
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<a id="1" class="mim-anchor"></a>
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<a id="Dauwerse2011" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Dauwerse, J. G., Dixon, J., Seland, S., Ruivenkamp, C. A. L., van Haeringen, A., Hoefsloot, L. H., Peters, D. J. M., Clement-de Boers, A., Daumer-Haas, C., Maiwald, R., Zweier, C., Kerr, B., Cobo, A. M., Toral, J. F., Hoogeboom, A. J. M., Lohmann, D. R., Hehr, U., Dixon, M. J., Breuning, M. H., Wieczorek, D.
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<strong>Mutations in gene encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome.</strong>
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Nature Genet. 43: 20-22, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21131976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21131976</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21131976" 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/ng.724" target="_blank">Full Text</a>]
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<a id="2" class="mim-anchor"></a>
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<a id="Hu2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Hu, P., Wu, S., Sun, Y., Yuan, C.-C., Kobayashi, R., Myers, M. P., Hernandez, N.
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<strong>Characterization of human RNA polymerase III identifies orthologues for Saccharomyces cerevisiae RNA polymerase III subunits.</strong>
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Molec. Cell. Biol. 22: 8044-8055, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12391170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12391170</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12391170[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=12391170" 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/10.1128/MCB.22.22.8044-8055.2002" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="3" class="mim-anchor"></a>
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<a id="Mao1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Mao, M., Fu, G., Wu, J.-S., Zhang, Q.-H., Zhou, J., Kan, L.-X., Huang, Q.-H., He, K.-L., Gu, B.-W., Han, Z.-G., Shen, Y., Gu, J., Yu, Y.-P., Xu, S.-H., Wang, Y.-X., Chen, S.-J., Chen, Z.
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<strong>Identification of genes expressed in human CD34+ hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning.</strong>
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Proc. Nat. Acad. Sci. 95: 8175-8180, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9653160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9653160</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9653160" 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.95.14.8175" target="_blank">Full Text</a>]
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<li>
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<a id="4" class="mim-anchor"></a>
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<a id="Splendore2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Splendore, A., Silva, E. O., Alonso, L. G., Richieri-Costa, A., Alonso, N., Rosa, A., Carakushanky, G., Cavalcanti, D. P., Brunoni, D., Passos-Bueno, M. R.
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<strong>High mutation detection rate in TCOF1 among Treacher Collins syndrome patients reveals clustering of mutations and 16 novel pathogenic changes.</strong>
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Hum. Mutat. 16: 315-322, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11013442/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11013442</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11013442" 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/10.1002/1098-1004(200010)16:4<315::AID-HUMU4>3.0.CO;2-H" target="_blank">Full Text</a>]
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Stumpf, A. M.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 02/21/2022.
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<a id="Thiffault2015" class="mim-anchor"></a>
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<p class="mim-text-font">
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Thiffault, I., Wolf, N. I., Forget, D., Guerrero, K., Tran, L. T., Choquet, K., Lavallee-Adam, M., Poitras, C., Brais, B., Yoon, G., Sztriha, L., Webster, R. I., and 15 others.
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<strong>Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III.</strong>
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Nature Commun. 6: 7623, 2015. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26151409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26151409</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26151409[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=26151409" 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/ncomms8623" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Anne M. Stumpf - updated : 02/21/2022
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 7/29/2015<br>Marla J. F. O'Neill - updated : 1/28/2011
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Creation Date:
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<span class="mim-text-font">
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Patricia A. Hartz : 4/18/2006
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alopez : 02/21/2022
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<span class="mim-text-font">
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carol : 04/04/2017<br>alopez : 10/05/2016<br>carol : 07/29/2015<br>mcolton : 7/29/2015<br>ckniffin : 7/29/2015<br>carol : 1/28/2011<br>carol : 1/28/2011<br>terry : 1/28/2011<br>mgross : 4/18/2006
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<strong>*</strong> 610060
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<h3>
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<span class="mim-font">
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POLYMERASE I, RNA, SUBUNIT C; POLR1C
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<em>Alternative titles; symbols</em>
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RPA39<br />
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RPA40<br />
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RPAC1<br />
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RPA5
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<strong><em>HGNC Approved Gene Symbol: POLR1C</em></strong>
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Cytogenetic location: 6p21.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 6:43,517,089-43,562,407 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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<strong>Gene-Phenotype Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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<th>
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Inheritance
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<th>
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Phenotype <br /> mapping key
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<tr>
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<td rowspan="2">
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<span class="mim-font">
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6p21.1
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<td>
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<span class="mim-font">
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Leukodystrophy, hypomyelinating, 11
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</td>
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<td>
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<span class="mim-font">
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616494
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Treacher Collins syndrome 3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
248390
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The POLR1C gene encodes a subunit that is shared by both RNA polymerase I (POLR1) and RNA polymerase III (POLR3) (summary by Thiffault et al., 2015). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By sequencing cDNAs obtained from umbilical cord blood CD34 (142230)-positive hematopoietic stem/progenitor cells, Mao et al. (1998) cloned POLR1C, which they called RPA40. The deduced protein contains 342 amino acids. </p><p>By sequencing proteins contained within RNA polymerase III complexes purified from HeLa cells, followed by database analysis, Hu et al. (2002) identified POLR1C, which they called RPAC1. The deduced 342-amino acid protein has a calculated molecular mass of 38.6 kD and shares 47% amino acid identity with its yeast homolog, AC40. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Stumpf (2022) mapped the POLR1C gene to chromosome 6p21.1 based on an alignment of the POLR1C sequence (GenBank BC008863) with the genomic sequence (GRCh38).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Treacher Collins Syndrome 3</em></strong></p><p>
|
|
Dauwerse et al. (2011) analyzed the POLR1C gene in 252 individuals with Treacher Collins syndrome (TCS3; 248390) and identified 3 patients with compound heterozygous mutations (610060.0001-610060.0005). </p><p><strong><em>Hypomyelinating Leukodystrophy 11</em></strong></p><p>
|
|
In 8 patients with hypomyelinating leukodystrophy-11 (HLD11; 616494) who were negative for mutations in the POLR3A (614258) and POLR3B (614366) genes, Thiffault et al. (2015) identified 13 homozygous or compound heterozygous mutations in the POLR1C gene (see, e.g., 610060.0006-610060.0011). Mutations in the first 3 patients were found by whole-exome sequencing and segregated with the disorder in the families. Subsequent mutations in 5 patients were found by direct sequencing of the POLR1C gene in 16 individuals with a similar phenotype who were negative for POLR3A and POLR3B mutations. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In in vitro functional expression assays in HeLa cells, Thiffault et al. (2015) found that the POLR1C R279Q mutation (610060.0001) associated with Treacher Collins syndrome did not affect the assembly of either RNA polymerase I or III. However, the R279Q mutation impaired targeting of the protein to the nucleolus, the site for RNA polymerase I gene transcription. In contrast, 2 missense mutations associated with HLD11 (N74S; 610060.0006 and N32I; 610060.0007) specifically interfered with assembly and nuclear import of RNA polymerase III, but not RNA polymerase I. The findings provided a pathophysiologic mechanism for the different clinical conditions resulting from different mutations in the same gene. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>11 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 TREACHER COLLINS SYNDROME 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
POLR1C, ARG279GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs191582628,
|
|
|
|
|
|
gnomAD: rs191582628,
|
|
|
|
|
|
ClinVar: RCV000023796, RCV000513700, RCV000788034, RCV002281718, RCV002504821, RCV002513205
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a sister and brother and an unrelated male patient with Treacher Collins syndrome-3 (TCS3; 248390), Dauwerse et al. (2011) identified compound heterozygosity for an 836G-A transition in exon 8 of the POLR1C gene, resulting in an arg279-to-gln (R279Q) substitution at a highly conserved residue in the RNA polymerase dimerization domain of POLR1C, and another mutation in POLR1C. The second mutation in the sister and her more severely affected brother, who had previously been studied by Splendore et al. (2000), was a 4-bp deletion in intron 8 (610060.0002) at the splice donor site (922+3_922+6del), predicted to result in skipping of exon 8. The unrelated patient's second mutation was a 979A-T transversion in exon 9, resulting in a lys327-to-ter (K327X; 610060.0003) substitution. The unrelated patient's unaffected parents were each heterozygous for 1 of the mutations; the sibs' unaffected mother and her healthy sister were heterozygous for the R279Q mutation, but DNA from their deceased father was unavailable for study. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 TREACHER COLLINS SYNDROME 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
POLR1C, IVS8, 4-BP DEL, +3
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1335699710,
|
|
|
|
|
|
|
|
ClinVar: RCV000023797
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 4-bp deletion in the POLR1C gene (922+3_922+6del) that was found in compound heterozygous state in sibs with Treacher Collins syndrome-3 (TCS3; 248390) by Dauwerse et al. (2011), see 610060.0001. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 TREACHER COLLINS SYNDROME 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
POLR1C, LYS327TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387907020,
|
|
|
|
|
|
gnomAD: rs387907020,
|
|
|
|
|
|
ClinVar: RCV000023798, RCV001090591
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the lys327-to-ter (K327X) mutation in the POLR1C gene that was found in compound heterozygous state in a patient with Treacher Collins syndrome-3 (TCS3; 248390) by Dauwerse et al. (2011), see 610060.0001. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 TREACHER COLLINS SYNDROME 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
POLR1C, 1-BP DEL, 87T
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2127686639,
|
|
|
|
|
|
|
|
ClinVar: RCV000023799
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a male patient with Treacher Collins syndrome-3 (TCS3; 248390), Dauwerse et al. (2011) identified compound heterozygosity for 2 mutations in the POLR1C gene: a 1-bp deletion (87delT) in exon 2, predicted to cause a frameshift and a premature termination codon, and an 835C-T transition in exon 8, resulting in an arg279-to-trp (R279W) substitution (610060.0005). His unaffected parents were each heterozygous for 1 of the mutations. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 TREACHER COLLINS SYNDROME 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
POLR1C, ARG279TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs141156009,
|
|
|
|
|
|
gnomAD: rs141156009,
|
|
|
|
|
|
ClinVar: RCV000023800, RCV000382254, RCV000788033, RCV005031454
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg279-to-trp (R279W) mutation in the POLR1C gene that was found in compound heterozygous state in a patient with Treacher Collins syndrome-3 (TCS3; 248390) by Dauwerse et al. (2011), see 610060.0004. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 LEUKODYSTROPHY, HYPOMYELINATING, 11</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
POLR1C, ASN74SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs371802902,
|
|
|
|
|
|
gnomAD: rs371802902,
|
|
|
|
|
|
ClinVar: RCV000186584, RCV001852434
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Hungarian boy with hypomyelinating leukodystrophy-11 (HLD11; 616494), Thiffault et al. (2015) identified a homozygous c.221A-G transition (c.221A-G, NM_203290) in exon 3 of the POLR1C gene, resulting in an asn74-to-ser (N74S) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was found at a very low frequency (less than 0.01%) in the Exome Sequencing Project and ExAC databases and was not found in the CEPH database. In vitro functional expression studies in HeLa cells showed that the mutant protein interacted less well with POLR3 than did wildtype, suggesting a selective defect in POLR3 assembly that did not affect POLR1 assembly. Immunofluorescence and immunoprecipitation studies showed cytoplasmic accumulation of mutated POLR1C subunits and reduced binding to POLR3-transcribed genes. In contrast, there was no difference between mutant and wildtype POLR1C in binding to POLR1-transcribed genes. The findings indicated that the N74S mutation specifically interfered with assembly, nuclear import, and chromatin association of POLR3. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 LEUKODYSTROPHY, HYPOMYELINATING, 11</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
POLR1C, ASN32ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs796052124,
|
|
|
|
|
|
|
|
ClinVar: RCV000186585
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy, born of consanguineous Libyan parents, with hypomyelinating leukodystrophy-11 (HLD11; 616494), Thiffault et al. (2015) identified a homozygous c.95A-T transversion (c.95A-T, NM_203290) in exon 2 of the POLR1C gene, resulting in an asn32-to-ile (N32I) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the Exome Sequencing Project, ExAC, or CEPH databases. In vitro functional expression studies in HeLa cells showed that the mutant protein interacted less well with POLR3 than did wildtype, suggesting a selective defect in POLR3 assembly that did not affect POLR1 assembly. Immunofluorescence and immunoprecipitation studies showed cytoplasmic accumulation of mutated POLR1C subunits and reduced binding to POLR3-transcribed genes. In contrast, there was no difference between mutant and wildtype POLR1C in binding to POLR1-transcribed genes. The findings indicated that the N32I mutation specifically interfered with assembly, nuclear import, and chromatin association of POLR3. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 LEUKODYSTROPHY, HYPOMYELINATING, 11</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
POLR1C, CYS146ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs796052125,
|
|
|
|
|
|
|
|
ClinVar: RCV000186586
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Chinese boy with hypomyelinating leukodystrophy-11 (HLD11; 616494), Thiffault et al. (2015) identified compound heterozygous mutations in the POLR1C gene: a c.436T-C transition (c.436T-C, NM_203290) in exon 5, resulting in a cys146-to-arg (C146R) substitution at a highly conserved residue, and a 3-bp deletion in exon 8 (c.883_885delAAG; 610060.0009), resulting in an in-frame deletion of a conserved residue (Lys295del). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and were not found in the Exome Sequencing Project, ExAC, or CEPH databases. Functional studies of the variants were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 LEUKODYSTROPHY, HYPOMYELINATING, 11</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
POLR1C, 3-BP DEL, 883AAG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs875989826,
|
|
|
|
|
|
|
|
ClinVar: RCV000186587, RCV000483343, RCV004689662, RCV005031724
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
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<p>For discussion of the c.883_885delAAG (c.883_885delAAG, NM_203290) mutation in the POLR1C gene that was found in compound heterozygous state in a patient with hypomyelinating leukodystrophy-11 (HLD11; 616494) by Thiffault et al. (2015), see 610060.0008. </p>
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<h4>
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<span class="mim-font">
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<strong>.0010 LEUKODYSTROPHY, HYPOMYELINATING, 11</strong>
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POLR1C, THR26ILE
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<br />
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SNP: rs796052126,
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ClinVar: RCV000186588
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<p>In a girl with hypomyelinating leukodystrophy-11 (HLD11; 616494), Thiffault et al. (2015) identified compound heterozygous mutations in the POLR1C gene: a c.77C-T transition (c.77C-T, NM_203290) in exon 2, resulting in a thr26-to-ile (T26I) substitution, and a c.326G-A transition in exon 4, resulting in an arg109-to-his (R109H; 610060.0011) substitution. Each unaffected parent was heterozygous for 1 of the mutations. Both mutations occurred at conserved residues. The variants were not found in the Exome Variant Server, Exome Aggregation Consortium, or CEPH databases, and functional studies were not performed. </p>
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<span class="mim-font">
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<strong>.0011 LEUKODYSTROPHY, HYPOMYELINATING, 11</strong>
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</span>
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<span class="mim-text-font">
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POLR1C, ARG109HIS
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<br />
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SNP: rs796052127,
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gnomAD: rs796052127,
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ClinVar: RCV000186589, RCV000853238, RCV003387792
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<span class="mim-text-font">
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<p>For discussion of the c.326G-A transition (c.326G-A, NM_203290) in the POLR1C gene, resulting in an arg109-to-his (R109H) substitution, that was found in compound heterozygous state in a patient with hypomyelinating leukodystrophy-11 (HLD11; 616494) by Thiffault et al. (2015), see 610060.0010. </p>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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</div>
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<ol>
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<li>
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Dauwerse, J. G., Dixon, J., Seland, S., Ruivenkamp, C. A. L., van Haeringen, A., Hoefsloot, L. H., Peters, D. J. M., Clement-de Boers, A., Daumer-Haas, C., Maiwald, R., Zweier, C., Kerr, B., Cobo, A. M., Toral, J. F., Hoogeboom, A. J. M., Lohmann, D. R., Hehr, U., Dixon, M. J., Breuning, M. H., Wieczorek, D.
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<strong>Mutations in gene encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome.</strong>
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Nature Genet. 43: 20-22, 2011.
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[PubMed: 21131976]
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[Full Text: https://doi.org/10.1038/ng.724]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Hu, P., Wu, S., Sun, Y., Yuan, C.-C., Kobayashi, R., Myers, M. P., Hernandez, N.
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<strong>Characterization of human RNA polymerase III identifies orthologues for Saccharomyces cerevisiae RNA polymerase III subunits.</strong>
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Molec. Cell. Biol. 22: 8044-8055, 2002.
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[PubMed: 12391170]
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[Full Text: https://doi.org/10.1128/MCB.22.22.8044-8055.2002]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Mao, M., Fu, G., Wu, J.-S., Zhang, Q.-H., Zhou, J., Kan, L.-X., Huang, Q.-H., He, K.-L., Gu, B.-W., Han, Z.-G., Shen, Y., Gu, J., Yu, Y.-P., Xu, S.-H., Wang, Y.-X., Chen, S.-J., Chen, Z.
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<strong>Identification of genes expressed in human CD34+ hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning.</strong>
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Proc. Nat. Acad. Sci. 95: 8175-8180, 1998.
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[PubMed: 9653160]
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[Full Text: https://doi.org/10.1073/pnas.95.14.8175]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Splendore, A., Silva, E. O., Alonso, L. G., Richieri-Costa, A., Alonso, N., Rosa, A., Carakushanky, G., Cavalcanti, D. P., Brunoni, D., Passos-Bueno, M. R.
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<strong>High mutation detection rate in TCOF1 among Treacher Collins syndrome patients reveals clustering of mutations and 16 novel pathogenic changes.</strong>
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Hum. Mutat. 16: 315-322, 2000.
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[PubMed: 11013442]
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[Full Text: https://doi.org/10.1002/1098-1004(200010)16:4<315::AID-HUMU4>3.0.CO;2-H]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Stumpf, A. M.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 02/21/2022.
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Thiffault, I., Wolf, N. I., Forget, D., Guerrero, K., Tran, L. T., Choquet, K., Lavallee-Adam, M., Poitras, C., Brais, B., Yoon, G., Sztriha, L., Webster, R. I., and 15 others.
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<strong>Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III.</strong>
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Nature Commun. 6: 7623, 2015. Note: Electronic Article.
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[PubMed: 26151409]
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[Full Text: https://doi.org/10.1038/ncomms8623]
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</p>
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</li>
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</ol>
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<div>
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<br />
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<span class="mim-text-font">
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Anne M. Stumpf - updated : 02/21/2022<br>Cassandra L. Kniffin - updated : 7/29/2015<br>Marla J. F. O'Neill - updated : 1/28/2011
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</span>
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Patricia A. Hartz : 4/18/2006
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