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Entry
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- *608667 - NIPPED-B-LIKE; NIPBL
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- OMIM
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<div class="container hidden-print">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*608667</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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</li>
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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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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#biochemicalFeatures">Biochemical Features</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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<li role="presentation" style="margin-left: 1em">
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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</li>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/608667">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>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000164190;t=ENST00000282516" 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=25836" 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=608667" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000164190;t=ENST00000282516" 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_015384,NM_133433,XM_005248280,XM_005248282,XM_006714467,XM_006714468,XM_011514015,XM_017009329" 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_133433" 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=608667" 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=10560&isoform_id=10560_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/NIPBL" 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/21708155,31874624,31874626,34364676,34533437,47458031,47578105,47578107,48143958,48143963,50400865,119576352,119576353,119576354,124297051,152001136,158261717,530378760,578809901,578809903,767934368,1034644501,1034644503,2462601980,2462601982,2462601984,2462601986,2462601988,2462601990" 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/Q6KC79" 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=25836" 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=ENSG00000164190;t=ENST00000282516" 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=NIPBL" 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=NIPBL" 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+25836" 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/NIPBL" 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:25836" 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/25836" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr5&hgg_gene=ENST00000282516.13&hgg_start=36876769&hgg_end=37066413&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:28862" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:28862" 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/nipbl" 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=608667[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=608667[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/NIPBL/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/ENSG00000164190" 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=NIPBL" 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=NIPBL" 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=NIPBL" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://www.LOVD.nl/NIPBL" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=NIPBL&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/PA134962343" 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:28862" 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/FBgn0026401.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:1913976" 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/NIPBL#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:1913976" 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/25836/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=25836" 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=WBGene00004166;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-030131-6070" 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="mimCellLines">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" 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="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</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="mimCellLinesLinksFold" 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://catalog.coriell.org/Search?q=OmimNum:608667" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</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:25836" 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=NIPBL&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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608667
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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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NIPPED-B-LIKE; NIPBL
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
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NIPPED-B, DROSOPHILA, HOMOLOG OF<br />
|
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DELANGIN<br />
|
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SISTER CHROMATID COHESION 2, S. CEREVISIAE, HOMOLOG OF; SCC2
|
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</span>
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=NIPBL" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">NIPBL</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">
|
|
<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/5/115?start=-3&limit=10&highlight=115">5p13.2</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr5:36876769-37066413&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">5:36,876,769-37,066,413</a> </span>
|
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</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
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</div>
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<div>
|
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<br />
|
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</div>
|
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<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
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<th>
|
|
Phenotype
|
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</th>
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<th>
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|
Phenotype <br /> MIM number
|
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</th>
|
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<th>
|
|
Inheritance
|
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</th>
|
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<th>
|
|
Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
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</thead>
|
|
<tbody>
|
|
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
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<p>Sister chromatids remain connected following duplication in S phase until they segregate during anaphase of mitosis or meiosis II. This cohesion counteracts the force of spindle microtubules on sister kinetochores and allows chromosomes to align at the mitotic spindle. Sister chromatid cohesion is also essential for segregation of homologous chromosomes during meiosis I and for repair of DNA double-strand breaks during G2 phase. Cohesin (see <a href="/entry/606462">606462</a>) is a protein complex required for sister chromatid cohesion. NIPBL forms a dimer with MAU2 (<a href="/entry/614560">614560</a>) that is essential for loading the cohesin complex onto sister chromatids (<a href="#17" class="mim-tip-reference" title="Watrin, E., Schleiffer, A., Tanaka, K., Eisenhaber, F., Nasmyth, K., Peters, J.-M. <strong>Human Scc4 is required for cohesin binding to chromatin, sister-chromatid cohesion, and mitotic progression.</strong> Curr. Biol. 16: 863-874, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16682347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16682347</a>] [<a href="https://doi.org/10.1016/j.cub.2006.03.049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16682347">Watrin et al., 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16682347" 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 the course of searching for the molecular basis of Cornelia de Lange syndrome (CDLS1; <a href="/entry/122470">122470</a>), <a href="#16" class="mim-tip-reference" title="Tonkin, E. T., Wang, T.-J., Lisgo, S., Bamshad, M. J., Strachan, T. <strong>NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.</strong> Nature Genet. 36: 636-641, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146185</a>] [<a href="https://doi.org/10.1038/ng1363" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146185">Tonkin et al. (2004)</a> and <a href="#9" class="mim-tip-reference" title="Krantz, I. D., McCallum, J., DeScipio, C., Kaur, M., Gillis, L. A., Yaeger, D., Jukofsky, L., Wasserman, N., Bottani, A., Morris, C. A., Nowaczyk, M. J. M., Toriello, H., and 9 others. <strong>Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B.</strong> Nature Genet. 36: 631-635, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146186</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15146186[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/ng1364" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146186">Krantz et al. (2004)</a> analyzed de novo balanced translocations associated with Cornelia de Lange syndrome and identified a novel gene at 5p13.1 that is disrupted in these cases. <a href="#16" class="mim-tip-reference" title="Tonkin, E. T., Wang, T.-J., Lisgo, S., Bamshad, M. J., Strachan, T. <strong>NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.</strong> Nature Genet. 36: 636-641, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146185</a>] [<a href="https://doi.org/10.1038/ng1363" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146185">Tonkin et al. (2004)</a> designated the product of the Nipped-B-like (NIPBL) gene 'delangin.' The coding sequence commences in exon 2 and continues either to exon 47, generating a long isoform (2,804 amino acids), or to an expanded variant of exon 46, generating a slightly shorter isoform (2,697 amino acids). Residues 1 through 2,683 of the short and long isoforms are identical; the short isoform contains a 14-amino acid C-terminal end that is unrelated to the 121-amino acid C-terminal end of the long isoform (<a href="#16" class="mim-tip-reference" title="Tonkin, E. T., Wang, T.-J., Lisgo, S., Bamshad, M. J., Strachan, T. <strong>NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.</strong> Nature Genet. 36: 636-641, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146185</a>] [<a href="https://doi.org/10.1038/ng1363" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146185">Tonkin et al., 2004</a>). Northern blot analysis showed that NIPBL is strongly expressed in fetal and adult kidney, fetal liver, adult placenta, heart, skeletal muscle, and thymus, but weakly or almost undetectably expressed in fetal and adult brain and lung and in adult liver, colon, small intestine, and leukocytes (<a href="#16" class="mim-tip-reference" title="Tonkin, E. T., Wang, T.-J., Lisgo, S., Bamshad, M. J., Strachan, T. <strong>NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.</strong> Nature Genet. 36: 636-641, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146185</a>] [<a href="https://doi.org/10.1038/ng1363" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146185">Tonkin et al., 2004</a>). <a href="#16" class="mim-tip-reference" title="Tonkin, E. T., Wang, T.-J., Lisgo, S., Bamshad, M. J., Strachan, T. <strong>NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.</strong> Nature Genet. 36: 636-641, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146185</a>] [<a href="https://doi.org/10.1038/ng1363" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146185">Tonkin et al. (2004)</a> found that vertebrate delangins have substantial homology to orthologs in flies, worms, plants, and fungi, including Scc2-type sister chromatid cohesion proteins, and D. melanogaster Nipped-B. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15146185+15146186" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using bioinformatic analysis, <a href="#18" class="mim-tip-reference" title="Yan, J., Saifi, G. M., Wierzba, T. H., Withers, M., Bien-Willner, G. A., Limon, J., Stankiewicz, P., Lupski, J. R., Wierzba, J. <strong>Mutational and genotype-phenotype correlation analyses in 28 Polish patients with Cornelia de Lange syndrome.</strong> Am. J. Med. Genet. 140A: 1531-1541, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16770807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16770807</a>] [<a href="https://doi.org/10.1002/ajmg.a.31305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16770807">Yan et al. (2006)</a> showed that NIPBL protein contains an N-terminal caldesmon (CALD1; <a href="/entry/114213">114213</a>) domain, a calponin (CNN1; <a href="/entry/600806">600806</a>) domain, and 2 calmodulin (CALM1; <a href="/entry/114180">114180</a>)-binding motifs, followed by a nuclear localization signal, a nuclear export signal, 5 HEAT repeats, and a C-terminal DNA-binding domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16770807" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The NIPBL gene contains 47 exons spanning 188 kb, with commencement of the coding sequence in exon 2 (<a href="#9" class="mim-tip-reference" title="Krantz, I. D., McCallum, J., DeScipio, C., Kaur, M., Gillis, L. A., Yaeger, D., Jukofsky, L., Wasserman, N., Bottani, A., Morris, C. A., Nowaczyk, M. J. M., Toriello, H., and 9 others. <strong>Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B.</strong> Nature Genet. 36: 631-635, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146186</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15146186[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/ng1364" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146186">Krantz et al., 2004</a>; <a href="#16" class="mim-tip-reference" title="Tonkin, E. T., Wang, T.-J., Lisgo, S., Bamshad, M. J., Strachan, T. <strong>NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.</strong> Nature Genet. 36: 636-641, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146185</a>] [<a href="https://doi.org/10.1038/ng1363" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146185">Tonkin et al., 2004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15146185+15146186" 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="#9" class="mim-tip-reference" title="Krantz, I. D., McCallum, J., DeScipio, C., Kaur, M., Gillis, L. A., Yaeger, D., Jukofsky, L., Wasserman, N., Bottani, A., Morris, C. A., Nowaczyk, M. J. M., Toriello, H., and 9 others. <strong>Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B.</strong> Nature Genet. 36: 631-635, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146186</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15146186[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/ng1364" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146186">Krantz et al. (2004)</a> and <a href="#16" class="mim-tip-reference" title="Tonkin, E. T., Wang, T.-J., Lisgo, S., Bamshad, M. J., Strachan, T. <strong>NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.</strong> Nature Genet. 36: 636-641, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146185</a>] [<a href="https://doi.org/10.1038/ng1363" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146185">Tonkin et al. (2004)</a> identified the NIPBL gene within chromosome 5p13. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15146185+15146186" 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 situ hybridization to whole mouse embryos detected Nipbl transcripts at gestation days 9.5 and 10.5, with notable accumulations in limb bud, branchial arch, and craniofacial mesenchyme (<a href="#9" class="mim-tip-reference" title="Krantz, I. D., McCallum, J., DeScipio, C., Kaur, M., Gillis, L. A., Yaeger, D., Jukofsky, L., Wasserman, N., Bottani, A., Morris, C. A., Nowaczyk, M. J. M., Toriello, H., and 9 others. <strong>Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B.</strong> Nature Genet. 36: 631-635, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146186</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15146186[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/ng1364" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146186">Krantz et al., 2004</a>). In situ hybridization to human embryonic tissue sections revealed an expression pattern largely consistent with the CDLS phenotype (<a href="#16" class="mim-tip-reference" title="Tonkin, E. T., Wang, T.-J., Lisgo, S., Bamshad, M. J., Strachan, T. <strong>NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.</strong> Nature Genet. 36: 636-641, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146185</a>] [<a href="https://doi.org/10.1038/ng1363" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146185">Tonkin et al., 2004</a>). <a href="#9" class="mim-tip-reference" title="Krantz, I. D., McCallum, J., DeScipio, C., Kaur, M., Gillis, L. A., Yaeger, D., Jukofsky, L., Wasserman, N., Bottani, A., Morris, C. A., Nowaczyk, M. J. M., Toriello, H., and 9 others. <strong>Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B.</strong> Nature Genet. 36: 631-635, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146186</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15146186[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/ng1364" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146186">Krantz et al. (2004)</a> found evidence for alternative splicing of the NIPBL gene in the presence of multiple transcripts detected on Northern blot analysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15146185+15146186" 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>The evolution of an ancestral sister chromatid cohesion protein to acquire an additional role in developmental gene regulation suggested to <a href="#16" class="mim-tip-reference" title="Tonkin, E. T., Wang, T.-J., Lisgo, S., Bamshad, M. J., Strachan, T. <strong>NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.</strong> Nature Genet. 36: 636-641, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146185</a>] [<a href="https://doi.org/10.1038/ng1363" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146185">Tonkin et al. (2004)</a> that there are parallels between CDLS and Roberts syndrome (<a href="/entry/268300">268300</a>), which is characterized by growth retardation, limb reduction defects, craniofacial abnormalities, and premature centromere separation. A dual role for Nipped-B in sister chromatid cohesion and developmental regulation was confirmed by <a href="#12" class="mim-tip-reference" title="Rollins, R. A., Korom, M., Aulner, N., Martens, A., Dorsett, D. <strong>Drosophila Nipped-B protein supports sister chromatid cohesion and opposes the Stromalin/Scc3 cohesion factor to facilitate long-range activation of the cut gene.</strong> Molec. Cell. Biol. 24: 3100-3111, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15060134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15060134</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15060134[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.24.8.3100-3111.2004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15060134">Rollins et al. (2004)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15146185+15060134" 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 metaphase spread analysis, <a href="#6" class="mim-tip-reference" title="Kaur, M., DeScipio, C., McCallum, J., Yaeger, D., Devoto, M., Jackson, L. G., Spinner, N. B., Krantz, I. D. <strong>Precocious sister chromatid separation (PSCS) in Cornelia de Lange syndrome.</strong> Am. J. Med. Genet. 138A: 27-31, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16100726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16100726</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16100726[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.30919" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16100726">Kaur et al. (2005)</a> found evidence of precocious sister chromatid separation (PSCS) in 37 (41%) of 90 probands with CDLS compared to 8 (9%) of controls. Of the 37 CDLS patients with PSCS, 16 (43%) had mutations in the NIPBL gene, whereas 21 (57%) did not. Both severe and mild phenotypes were seen in those with PSCS and those without PSCS. <a href="#6" class="mim-tip-reference" title="Kaur, M., DeScipio, C., McCallum, J., Yaeger, D., Devoto, M., Jackson, L. G., Spinner, N. B., Krantz, I. D. <strong>Precocious sister chromatid separation (PSCS) in Cornelia de Lange syndrome.</strong> Am. J. Med. Genet. 138A: 27-31, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16100726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16100726</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16100726[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.30919" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16100726">Kaur et al. (2005)</a> noted that Roberts syndrome (<a href="/entry/268300">268300</a>), which has phenotypic overlap with CDLS and is associated with premature sister chromatid separation, is caused by mutations in the ESCO2 gene (<a href="/entry/609353">609353</a>), which is required for proper establishment of the sister chromatid cohesion complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16100726" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using immunoprecipitation analysis, <a href="#17" class="mim-tip-reference" title="Watrin, E., Schleiffer, A., Tanaka, K., Eisenhaber, F., Nasmyth, K., Peters, J.-M. <strong>Human Scc4 is required for cohesin binding to chromatin, sister-chromatid cohesion, and mitotic progression.</strong> Curr. Biol. 16: 863-874, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16682347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16682347</a>] [<a href="https://doi.org/10.1016/j.cub.2006.03.049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16682347">Watrin et al. (2006)</a> showed that SCC4 (MAU2; <a href="/entry/614560">614560</a>) interacted with SCC2 in HeLa cell nucleoplasmic extracts. SCC4 and SCC2 cosedimented in fractionated HeLa cell extracts and colocalized on chromatin in HeLa cells during interphase and telophase. Depletion of either SCC4 or SCC2 via small interfering RNA delayed mitotic exit and caused loss of cohesin from chromatin during interphase and telophase, precocious loss of sister chromatid cohesion, misalignment of chromosomes, appearance of single sister chromatids, and prometaphase arrest. Knockdown of either SCC4 or SCC2 also reduced the amount of the other protein, suggesting that physical association between them is required for stability. Chromosomes in SCC4- or SCC2-depleted cells lacked cohesin despite the presence of the cohesin protectors SGO1 (SGOL1; <a href="/entry/609168">609168</a>) and BUB1 (<a href="/entry/602452">602452</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16682347" 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>Independently, <a href="#14" class="mim-tip-reference" title="Seitan, V. C., Banks, P., Laval, S., Majid, N. A., Dorsett, D., Rana, A., Smith, J., Bateman, A., Krpic, S., Hostert, A., Rollins, R. A., Erdjument-Bromage, H., Tempst, P., Benard, C. Y., Hekimi, S., Newbury, S. F., Strachan, T. <strong>Metazoan Scc4 homologs link sister chromatid cohesion to cell and axon migration guidance.</strong> PLoS Biol. 4: e242, 2006. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16802858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16802858</a>] [<a href="https://doi.org/10.1371/journal.pbio.0040242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16802858">Seitan et al. (2006)</a> showed that MAU2 coimmunoprecipitated with delangin. Drosophila and Xenopus orthologs of MAU2 and delangin also interacted directly. Protein truncation and yeast 2-hybrid analyses revealed that the N termini of MAU2 and delangin mediated their interaction. Knockdown of MAU2 in HeLa cells resulted in increased frequency of precocious sister chromatid separation. In control cells, release from block in G2/M resulted in rapid loading of cohesin subunits onto chromatin. In MAU2 knockdown cells, cohesin complexes formed, but they failed to load onto chromatin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16802858" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Kagey, M. H., Newman, J. J., Bilodeau, S., Zhan, Y., Orlando, D. A., van Berkum, N. L., Ebmeier, C. C., Goossens, J., Rahl, P. B., Levine, S. S., Taatjes, D. J., Dekker, J., Young, R. A. <strong>Mediator and cohesin connect gene expression and chromatin architecture.</strong> Nature 467: 430-435, 2010. Note: Erratum: Nature 472: 247 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20720539/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20720539</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20720539[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/nature09380" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20720539">Kagey et al. (2010)</a> reported that Mediator (see MED8, <a href="/entry/607956">607956</a>) and cohesin (see SMC1, <a href="/entry/300040">300040</a>) physically and functionally connect the enhancers and core promoters of active genes in murine embryonic stem cells. Mediator, a transcriptional coactivator, forms a complex with cohesin, which can form rings that connect 2 DNA segments. The cohesin-loading factor NIPBL is associated with Mediator-cohesin complexes, providing a means to load cohesin at promoters. DNA looping is observed between the enhancers and promoters occupied by Mediator and cohesin. Mediator and cohesin co-occupy different promoters in different cells, thus generating cell type-specific DNA loops linked to the gene expression program of each cell. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20720539" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In yeast, <a href="#11" class="mim-tip-reference" title="Lopez-Serra, L., Kelly, G., Patel, H., Stewart, A., Uhlmann, F. <strong>The Scc2-Scc4 complex acts in sister chromatid cohesion and transcriptional regulation by maintaining nucleosome-free regions.</strong> Nature Genet. 46: 1147-1151, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25173104/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25173104</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25173104[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/ng.3080" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25173104">Lopez-Serra et al. (2014)</a> found that the RSC chromatin-remodeling complex recruited Scc2-Scc4 dimers to broad, shallow nucleosome-free regions. Here, Scc2-Scc4 maintained the accessible DNA for the subsequent cohesin-loading reaction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25173104" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Schwarzer, W., Abdennur, N., Goloborodko, A., Pekowska, A., Fudenberg, G., Loe-Mie, Y., Fonseca, N. A., Huber, W., Haering, C. H., Mirny, L., Spitz, F. <strong>Two independent modes of chromatin organization revealed by cohesin removal.</strong> Nature 551: 51-56, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29094699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29094699</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29094699[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/nature24281" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29094699">Schwarzer et al. (2017)</a> found that deletion of the cohesin-loading factor Nipbl in mouse liver led to a marked reorganization of chromosomal folding. Topologically associating domains (TADs) and associated chromosome conformation capture (Hi-C) peaks vanished globally, even in the absence of transcriptional changes. By contrast, compartmental segregation was preserved and even reinforced. Strikingly, the disappearance of TADs unmasked a finer compartment structure that accurately reflects the underlying epigenetic landscape. These observations demonstrated that the 3-dimensional organization of the genome results from the interplay of 2 independent mechanisms: cohesin-independent segregation of the genome into fine-scale compartments, defined by chromatin state, and cohesin-dependent formation of TADs, possibly by loop extrusion, which helps to guide distant enhancers to their target genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29094699" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using biochemical reconstitution, <a href="#3" class="mim-tip-reference" title="Davidson, I. F., Bauer, B., Goetz, D., Tang, W., Wutz, G., Peters, J. M. <strong>DNA loop extrusion by human cohesin.</strong> Science 366: 1338-1345, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31753851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31753851</a>] [<a href="https://doi.org/10.1126/science.aaz3418" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31753851">Davidson et al. (2019)</a> found that single human cohesin complexes form DNA loops symmetrically at rates up to 2.1 kilobase pairs per second. Loop formation and maintenance depend on cohesin's ATPase activity and on NIPBL-MAU2 (<a href="/entry/614560">614560</a>), but not on topologic entrapment of DNA by cohesin (components include SMC3, <a href="/entry/606062">606062</a>; SMC1A, <a href="/entry/300040">300040</a>; STAG1, <a href="/entry/604358">604358</a>; STAG2, <a href="/entry/300826">300826</a>). During loop formation, cohesin and NIPBL-MAU2 reside at the base of loops, which indicates that they generate loops by extrusion. <a href="#3" class="mim-tip-reference" title="Davidson, I. F., Bauer, B., Goetz, D., Tang, W., Wutz, G., Peters, J. M. <strong>DNA loop extrusion by human cohesin.</strong> Science 366: 1338-1345, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31753851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31753851</a>] [<a href="https://doi.org/10.1126/science.aaz3418" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31753851">Davidson et al. (2019)</a> concluded that their results showed that cohesin and NIPBL-MAU2 form an active holoenzyme that interacts with DNA either pseudotopologically or nontopologically to extrude genomic interphase DNA into loops. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31753851" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Kim, Y., Shi, Z., Zhang, H., Finkelstein, I. J., Yu, H. <strong>Human cohesin compacts DNA by loop extrusion.</strong> Science 366: 1345-1349, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31780627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31780627</a>] [<a href="https://doi.org/10.1126/science.aaz4475" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31780627">Kim et al. (2019)</a> independently used single-molecule imaging to show that the recombinant human cohesin-NIPBL complex compacts both naked and nucleosome-bound DNA by extruding DNA loops. DNA compaction by cohesin requires ATP hydrolysis and is force-sensitive. This compaction is processive over tens of kilobases at an average rate of 0.5 kilobases per second. Compaction of double-tethered DNA suggests that a cohesin dimer extrudes DNA loops bidirectionally. <a href="#7" class="mim-tip-reference" title="Kim, Y., Shi, Z., Zhang, H., Finkelstein, I. J., Yu, H. <strong>Human cohesin compacts DNA by loop extrusion.</strong> Science 366: 1345-1349, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31780627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31780627</a>] [<a href="https://doi.org/10.1126/science.aaz4475" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31780627">Kim et al. (2019)</a> concluded that their results established cohesin-NIPBL as an ATP-driven molecular machine capable of loop extrusion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31780627" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using cryoelectron microscopy, <a href="#15" class="mim-tip-reference" title="Shi, Z., Gao, H., Bai, X., Yu, H. <strong>Cryo-EM structure of the human cohesin-NIPBL-DNA complex.</strong> Science 368: 1454-1459, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32409525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32409525</a>] [<a href="https://doi.org/10.1126/science.abb0981" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32409525">Shi et al. (2020)</a> determined the structure of human cohesin bound to the C-terminal HEAT domain of NIPBL and DNA at medium resolution. Cohesin and NIPBL interacted extensively and formed a central tunnel to entrap a 72-bp DNA. NIPBL and DNA promoted engagement of the ATPase head domains of cohesin and ATP binding. The hinge domains of cohesin adopted an 'open washer' conformation and docked onto the STAG1 subunit. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32409525" 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="#16" class="mim-tip-reference" title="Tonkin, E. T., Wang, T.-J., Lisgo, S., Bamshad, M. J., Strachan, T. <strong>NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.</strong> Nature Genet. 36: 636-641, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146185</a>] [<a href="https://doi.org/10.1038/ng1363" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146185">Tonkin et al. (2004)</a> studied CDLS cases without translocations and identified 9 plausible point mutations in the NIPBL gene, at least 5 of which arose de novo. As they found NIPBL mutations in individuals with severe and mild Cornelia de Lange syndrome-1 (CDLS1; <a href="/entry/122470">122470</a>), phenotypic variation may be explained in part by allelic heterogeneity. The spectrum and distribution of mutations implied that pathogenesis arose from loss or altered function of a single NIPBL allele. The mutation detection rate in the study of <a href="#16" class="mim-tip-reference" title="Tonkin, E. T., Wang, T.-J., Lisgo, S., Bamshad, M. J., Strachan, T. <strong>NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.</strong> Nature Genet. 36: 636-641, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146185</a>] [<a href="https://doi.org/10.1038/ng1363" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146185">Tonkin et al. (2004)</a> was approximately 50%. Thus, locus heterogeneity as well as allelic heterogeneity may be present, but limitations of the screening methods were also cited as a plausible explanation for the comparatively low mutation detection rate. On the other hand, considerable intrafamilial variation in phenotype of CDLS, even between affected sibs (<a href="#8" class="mim-tip-reference" title="Krajewska-Walasek, M., Chrzanowska, K., Tylki-Szymanska, A., Bialecka, M. <strong>A further report of Brachmann-de Lange syndrome in two sibs with normal parents.</strong> Clin. Genet. 47: 324-327, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7554368/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7554368</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1995.tb03974.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7554368">Krajewska-Walasek et al., 1995</a>), suggests that additional factors may be important. <a href="#16" class="mim-tip-reference" title="Tonkin, E. T., Wang, T.-J., Lisgo, S., Bamshad, M. J., Strachan, T. <strong>NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.</strong> Nature Genet. 36: 636-641, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146185</a>] [<a href="https://doi.org/10.1038/ng1363" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146185">Tonkin et al. (2004)</a> proposed that perturbed delangin function may inappropriately activate distal-less homeobox (DLX) genes, thereby contributing to the proximodistal limb patterning defects in CDLS. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15146185+7554368" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Krantz, I. D., McCallum, J., DeScipio, C., Kaur, M., Gillis, L. A., Yaeger, D., Jukofsky, L., Wasserman, N., Bottani, A., Morris, C. A., Nowaczyk, M. J. M., Toriello, H., and 9 others. <strong>Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B.</strong> Nature Genet. 36: 631-635, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146186</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15146186[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/ng1364" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146186">Krantz et al. (2004)</a> identified 6 point mutations in individuals with CDLS (<a href="#0001">608667.0001</a>-<a href="#0006">608667.0006</a>). All were expected to result in a truncated or, in the case of the met1-to-lys mutation (M1K; <a href="#0001">608667.0001</a>), an untranslated protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15146186" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Gillis, L. A., McCallum, J., Kaur, M., DeScipio, C., Yaeger, D., Mariani, A., Kline, A. D., Li, H., Devoto, M., Jackson, L. G., Krantz, I. D. <strong>NIPBL mutational analysis in 120 individuals with Cornelia de Lange syndrome and evaluation of genotype-phenotype correlations.</strong> Am. J. Hum. Genet. 75: 610-623, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15318302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15318302</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15318302[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/424698" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15318302">Gillis et al. (2004)</a> described the spectrum and distribution of NIPBL mutations in a large well-characterized cohort of individuals with CDLS. In 56 (47%) of 120 unrelated individuals with sporadic or familial CDLS, they identified mutations in the NIPBL gene (see <a href="#0007">608667.0007</a>-<a href="#0012">608667.0012</a>). In 49 (46%) of the 106 individuals with sporadic CDLS, 44 different mutations were identified, 14 (32%) of which were small deletions. In 6 the 7 familial cases of CDLS in which NIPBL mutations were identified, germline mosaicism was considered the likely mechanism for the occurrence of affected sibs with mutation-negative parents. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15318302" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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<a href="#2" class="mim-tip-reference" title="D'Alessandro, L. C. A., Al Turki, S., Manickaraj, A. K., Manase, D., Mulder, B. J. M., Bergin, L., Rosenberg, H. C., Mondal, T., Gordon, E., Lougheed, J., Smythe, J., Devriendt, K., UK10K Consortium, Bhattacharya, S., Watkins, H., Bentham, J., Bowdin, S., Hurles, M. E., Mital, S. <strong>Exome sequencing identifies rare variants in multiple genes in atrioventricular septal defect.</strong> Genet. Med. 18: 189-198, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25996639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25996639</a>] [<a href="https://doi.org/10.1038/gim.2015.60" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25996639">D'Alessandro et al. (2016)</a> performed whole-exome sequencing in 81 unrelated probands with atrioventricular septal defect (AVSD) to identify potential causal variants in a comprehensive set of 112 genes with strong biological relevance to AVSD. A significant enrichment of rare and rare damaging variants was identified in the gene set, compared with controls (odds ratio (OR) 1.52; 95% confidence interval (CI), 1.35-1.71; p = 4.8 x 10(-11)). The enrichment was specific to AVSD probands, compared with a cohort without AVSD with tetralogy of Fallot (OR 2.25; 95% CI, 1.84-2.76; p = 2.2 x 10(-16)). Six genes, including the syndrome-associated gene NIPBL, were enriched for rare variants in AVSD. The findings were confirmed in a replication cohort of 81 AVSD probands. <a href="#2" class="mim-tip-reference" title="D'Alessandro, L. C. A., Al Turki, S., Manickaraj, A. K., Manase, D., Mulder, B. J. M., Bergin, L., Rosenberg, H. C., Mondal, T., Gordon, E., Lougheed, J., Smythe, J., Devriendt, K., UK10K Consortium, Bhattacharya, S., Watkins, H., Bentham, J., Bowdin, S., Hurles, M. E., Mital, S. <strong>Exome sequencing identifies rare variants in multiple genes in atrioventricular septal defect.</strong> Genet. Med. 18: 189-198, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25996639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25996639</a>] [<a href="https://doi.org/10.1038/gim.2015.60" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25996639">D'Alessandro et al. (2016)</a> concluded that mutations in genes with strong biological relevance to AVSD, including syndrome-associated genes, can contribute to AVSD, even in those with isolated heart disease. Six AVSD probands (7.4%) had rare nonsynonymous variants in NIPBL compared with 2.3% in Exome Variant Server (EVS) controls (OR 3.3; p = 0.02). Two novel variants (M1318V and S2471T) involved highly conserved residues and were predicted to be damaging. Two variants (N105D and N393K) each previously occurred in a single individual among 4,300 EVS European American controls and not in other control data sets. None of the AVSD probands with NIPBL variants had clinical characteristics of CDLS. Two probands had associated semilunar valve anomalies, which are commonly associated with CDLS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25996639" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#4" class="mim-tip-reference" title="Gillis, L. A., McCallum, J., Kaur, M., DeScipio, C., Yaeger, D., Mariani, A., Kline, A. D., Li, H., Devoto, M., Jackson, L. G., Krantz, I. D. <strong>NIPBL mutational analysis in 120 individuals with Cornelia de Lange syndrome and evaluation of genotype-phenotype correlations.</strong> Am. J. Hum. Genet. 75: 610-623, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15318302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15318302</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15318302[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/424698" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15318302">Gillis et al. (2004)</a> found statistically significant phenotypic differences between NIPBL mutation-positive and NIPBL-negative individuals with CDLS. Analysis also suggested a trend toward a milder phenotype in individuals with missense mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15318302" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Yan, J., Saifi, G. M., Wierzba, T. H., Withers, M., Bien-Willner, G. A., Limon, J., Stankiewicz, P., Lupski, J. R., Wierzba, J. <strong>Mutational and genotype-phenotype correlation analyses in 28 Polish patients with Cornelia de Lange syndrome.</strong> Am. J. Med. Genet. 140A: 1531-1541, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16770807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16770807</a>] [<a href="https://doi.org/10.1002/ajmg.a.31305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16770807">Yan et al. (2006)</a> identified 13 different NIPBL mutations, including 11 novel mutations, in 13 (46%) of 28 Polish patients with a clinical diagnosis of CDLS. Eleven of the mutations resulted in a premature termination of the protein. Mutation-positive patients were more severely affected than mutation-negative patients with respect to prenatal growth, facial dysmorphism, and speech impairment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16770807" 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 3 sibs with Cornelia de Lange syndrome (CDLS1; <a href="/entry/122470">122470</a>), each with a different father, <a href="#9" class="mim-tip-reference" title="Krantz, I. D., McCallum, J., DeScipio, C., Kaur, M., Gillis, L. A., Yaeger, D., Jukofsky, L., Wasserman, N., Bottani, A., Morris, C. A., Nowaczyk, M. J. M., Toriello, H., and 9 others. <strong>Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B.</strong> Nature Genet. 36: 631-635, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146186</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15146186[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/ng1364" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146186">Krantz et al. (2004)</a> identified a start codon mutation, 2G-A (M1K), in the NIPBL gene. The mutation was not present in their mother or in the 2 fathers from whom samples were available. All 3 sibs, aged 17, 8, and 3 years, had moderate growth and cognitive delays, small hands without reduction defects, hirsutism, and typical facial features. Germline mosaicism was presumably the mechanism for the familial recurrence since the mother had not manifested features of the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15146186" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002222" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002222" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002222</a>
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<p>In an individual with classic features of Cornelia de Lange syndrome (CDLS1; <a href="/entry/122470">122470</a>), <a href="#16" class="mim-tip-reference" title="Tonkin, E. T., Wang, T.-J., Lisgo, S., Bamshad, M. J., Strachan, T. <strong>NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.</strong> Nature Genet. 36: 636-641, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146185</a>] [<a href="https://doi.org/10.1038/ng1363" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146185">Tonkin et al. (2004)</a> identified a 7289A-G transition in exon 43 of the NIPBL gene resulting in a tyr2430-to-cys (Y2430C) amino acid change in the delangin protein. The patient showed severe growth retardation, lobster limb defect, characteristic face, feeding difficulties, and gastroesophageal reflux. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15146185" 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">rs1554011042 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1554011042;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=rs1554011042" 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=rs1554011042" 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=RCV000002223" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002223" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002223</a>
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<p>In a child with Cornelia de Lange syndrome (CDLS1; <a href="/entry/122470">122470</a>), <a href="#9" class="mim-tip-reference" title="Krantz, I. D., McCallum, J., DeScipio, C., Kaur, M., Gillis, L. A., Yaeger, D., Jukofsky, L., Wasserman, N., Bottani, A., Morris, C. A., Nowaczyk, M. J. M., Toriello, H., and 9 others. <strong>Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B.</strong> Nature Genet. 36: 631-635, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146186</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15146186[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/ng1364" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146186">Krantz et al. (2004)</a> identified a 1-bp deletion, 150delG, in exon 3 of the NIPBL gene, resulting in frameshift with a stop codon 28 amino acids downstream. The male child, seen at 4.5 months of age, had severe bilateral upper limb reduction defects (oligodactyly, single digit), severe growth and cognitive delays, typical facial features, hirsutism, and cleft palate. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15146186" 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">rs1561222491 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1561222491;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=rs1561222491" 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=rs1561222491" 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=RCV000002224" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002224" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002224</a>
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<p>In a patient with classic features of Cornelia de Lange syndrome (CDLS1; <a href="/entry/122470">122470</a>), <a href="#16" class="mim-tip-reference" title="Tonkin, E. T., Wang, T.-J., Lisgo, S., Bamshad, M. J., Strachan, T. <strong>NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.</strong> Nature Genet. 36: 636-641, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146185</a>] [<a href="https://doi.org/10.1038/ng1363" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146185">Tonkin et al. (2004)</a> found a de novo 1-bp insertion, 7306_7307insG, in exon 43 of the NIPBL gene. The patient showed growth retardation, microbrachycephaly, long philtrum, thin lips, crescent-shaped mouth, synophrys, bushy eyebrows, general hirsutism, hearing impairment, myopia, micromelia, clinodactyly, proximally placed thumbs, fixed flexion of the elbows, syndactyly of the feet, bilateral inguinal hernias, and undescended testes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15146185" 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">rs1554016981 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1554016981;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=rs1554016981" 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=rs1554016981" 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=RCV000002225" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002225" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002225</a>
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<p>In an adult female with classic features of Cornelia de Lange syndrome (CDLS1; <a href="/entry/122470">122470</a>), <a href="#9" class="mim-tip-reference" title="Krantz, I. D., McCallum, J., DeScipio, C., Kaur, M., Gillis, L. A., Yaeger, D., Jukofsky, L., Wasserman, N., Bottani, A., Morris, C. A., Nowaczyk, M. J. M., Toriello, H., and 9 others. <strong>Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B.</strong> Nature Genet. 36: 631-635, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146186</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15146186[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/ng1364" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146186">Krantz et al. (2004)</a> identified a 1-bp insertion, 1546_1547insG, in exon 10 of the NIPBL gene. The insertion resulted in a frameshift with a stop codon 3 amino acids downstream. The patient showed severe growth and cognitive delays, reduction defect of the right limb (oligodactyly, 4 digits) and small left hand with no reduction defect, typical facial features, hirsutism, cleft palate, and hearing loss. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15146186" 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">rs121918266 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918266;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=rs121918266" 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=rs121918266" 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=RCV000002226" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002226" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002226</a>
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<p>In a patient with mild features of Cornelia de Lange syndrome (CDLS1; <a href="/entry/122470">122470</a>), <a href="#16" class="mim-tip-reference" title="Tonkin, E. T., Wang, T.-J., Lisgo, S., Bamshad, M. J., Strachan, T. <strong>NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.</strong> Nature Genet. 36: 636-641, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146185</a>] [<a href="https://doi.org/10.1038/ng1363" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146185">Tonkin et al. (2004)</a> described a 3-bp deletion of nucleotides 3616 through 3618 in exon 14 of the NIPBL gene (ATA) resulting in deletion of isoleucine-1206. The change was absent in maternal DNA; no paternal DNA was available. The patient showed growth retardation, small hands, microcephaly, speech delay, and inguinal hernia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15146185" 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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NIPBL, 2-BP DEL, 2479AG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs398124465 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398124465;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=rs398124465" 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=rs398124465" 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=RCV000082485 OR RCV000146547" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000082485, RCV000146547" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000082485...</a>
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<p>In 2 unrelated children with sporadic Cornelia de Lange syndrome (CDLS1; <a href="/entry/122470">122470</a>), <a href="#4" class="mim-tip-reference" title="Gillis, L. A., McCallum, J., Kaur, M., DeScipio, C., Yaeger, D., Mariani, A., Kline, A. D., Li, H., Devoto, M., Jackson, L. G., Krantz, I. D. <strong>NIPBL mutational analysis in 120 individuals with Cornelia de Lange syndrome and evaluation of genotype-phenotype correlations.</strong> Am. J. Hum. Genet. 75: 610-623, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15318302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15318302</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15318302[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/424698" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15318302">Gillis et al. (2004)</a> identified a 2-bp deletion in exon 10 of the NIPBL gene, 2479delAG, resulting in a frameshift and truncation of the protein 2 amino acids downstream. Both children were severely affected in terms of growth and development; however, one had significant limb reduction defects whereas the other did not. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15318302" 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">rs121918267 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918267;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=rs121918267" 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=rs121918267" 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=RCV000002228" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002228" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002228</a>
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<p>In 2 affected brothers from a family with Cornelia de Lange syndrome (CDLS1; <a href="/entry/122470">122470</a>), previously reported by <a href="#9" class="mim-tip-reference" title="Krantz, I. D., McCallum, J., DeScipio, C., Kaur, M., Gillis, L. A., Yaeger, D., Jukofsky, L., Wasserman, N., Bottani, A., Morris, C. A., Nowaczyk, M. J. M., Toriello, H., and 9 others. <strong>Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B.</strong> Nature Genet. 36: 631-635, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146186</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15146186[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/ng1364" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146186">Krantz et al. (2004)</a>, <a href="#4" class="mim-tip-reference" title="Gillis, L. A., McCallum, J., Kaur, M., DeScipio, C., Yaeger, D., Mariani, A., Kline, A. D., Li, H., Devoto, M., Jackson, L. G., Krantz, I. D. <strong>NIPBL mutational analysis in 120 individuals with Cornelia de Lange syndrome and evaluation of genotype-phenotype correlations.</strong> Am. J. Hum. Genet. 75: 610-623, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15318302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15318302</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15318302[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/424698" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15318302">Gillis et al. (2004)</a> identified an arg1723-to-ter (R1723X) substitution in exon 26 of the NIPBL gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15318302+15146186" 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">rs121918268 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918268;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=rs121918268" 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=rs121918268" 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=RCV000002229" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002229" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002229</a>
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<p><a href="#10" class="mim-tip-reference" title="Krantz, I. D., Tonkin, E., Smith, M., Devoto, M., Bottani, A., Simpson, C., Hofreiter, M., Abraham, V., Jukofsky, L., Conti, B. P., Strachan, T., Jackson, L. <strong>Exclusion of linkage to the CDL1 gene region on chromosome 3q26.3 in some familial cases of Cornelia de Lange syndrome.</strong> Am. J. Med. Genet. 101: 120-129, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11391654/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11391654</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11391654[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>]" pmid="11391654">Krantz et al. (2001)</a> described male first cousins from a family with Cornelia de Lange syndrome (CDLS1; <a href="/entry/122470">122470</a>), the sons of unaffected sisters, who were excluded from linkage analysis because of the atypical inheritance pattern. In the 2 affected males, <a href="#4" class="mim-tip-reference" title="Gillis, L. A., McCallum, J., Kaur, M., DeScipio, C., Yaeger, D., Mariani, A., Kline, A. D., Li, H., Devoto, M., Jackson, L. G., Krantz, I. D. <strong>NIPBL mutational analysis in 120 individuals with Cornelia de Lange syndrome and evaluation of genotype-phenotype correlations.</strong> Am. J. Hum. Genet. 75: 610-623, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15318302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15318302</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15318302[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/424698" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15318302">Gillis et al. (2004)</a> identified different de novo mutations in the NIPBL gene, neither of which was present in the parents: in one, an ala1246-to-gly (A1246G) substitution in exon 15, and in the other, a 7861G-C transversion at position -1 in the intron upstream of exon 46 (<a href="#0010">608667.0010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11391654+15318302" 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">rs1561231553 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1561231553;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=rs1561231553" 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=rs1561231553" 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 de novo 7861G-C transversion at position -1 in the intron upstream of exon 46 in the NIPBL gene that was found in compound heterozygous state in a patient with Cornelia de Lange syndrome-1 (CDLS1; <a href="/entry/122470">122470</a>) by <a href="#4" class="mim-tip-reference" title="Gillis, L. A., McCallum, J., Kaur, M., DeScipio, C., Yaeger, D., Mariani, A., Kline, A. D., Li, H., Devoto, M., Jackson, L. G., Krantz, I. D. <strong>NIPBL mutational analysis in 120 individuals with Cornelia de Lange syndrome and evaluation of genotype-phenotype correlations.</strong> Am. J. Hum. Genet. 75: 610-623, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15318302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15318302</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15318302[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/424698" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15318302">Gillis et al. (2004)</a>, see <a href="#0009">608667.0009</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15318302" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002231" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002231" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002231</a>
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<p>In affected members of a family with Cornelia de Lange syndrome (CDLS1; <a href="/entry/122470">122470</a>), previously described by <a href="#9" class="mim-tip-reference" title="Krantz, I. D., McCallum, J., DeScipio, C., Kaur, M., Gillis, L. A., Yaeger, D., Jukofsky, L., Wasserman, N., Bottani, A., Morris, C. A., Nowaczyk, M. J. M., Toriello, H., and 9 others. <strong>Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B.</strong> Nature Genet. 36: 631-635, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146186</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15146186[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/ng1364" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146186">Krantz et al. (2004)</a>, <a href="#4" class="mim-tip-reference" title="Gillis, L. A., McCallum, J., Kaur, M., DeScipio, C., Yaeger, D., Mariani, A., Kline, A. D., Li, H., Devoto, M., Jackson, L. G., Krantz, I. D. <strong>NIPBL mutational analysis in 120 individuals with Cornelia de Lange syndrome and evaluation of genotype-phenotype correlations.</strong> Am. J. Hum. Genet. 75: 610-623, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15318302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15318302</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15318302[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/424698" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15318302">Gillis et al. (2004)</a> identified a 7321A-G transition at position +4 of exon 43 of the NIPBL gene. The mutation was identified in 2 of 4 affected sibs from whom samples were available, as well as in the mildly affected mother. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15318302+15146186" 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">rs121918269 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918269;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=rs121918269" 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=rs121918269" 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=RCV000002232" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002232" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002232</a>
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<p>In 3 unrelated patients with sporadic Cornelia de Lange syndrome (CDLS1; <a href="/entry/122470">122470</a>), <a href="#4" class="mim-tip-reference" title="Gillis, L. A., McCallum, J., Kaur, M., DeScipio, C., Yaeger, D., Mariani, A., Kline, A. D., Li, H., Devoto, M., Jackson, L. G., Krantz, I. D. <strong>NIPBL mutational analysis in 120 individuals with Cornelia de Lange syndrome and evaluation of genotype-phenotype correlations.</strong> Am. J. Hum. Genet. 75: 610-623, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15318302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15318302</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15318302[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/424698" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15318302">Gillis et al. (2004)</a> identified an arg1536-to-ter (R1536X) substitution in exon 22 of the NIPBL gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15318302" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0013 CORNELIA DE LANGE SYNDROME 1</strong>
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NIPBL, 2-BP DEL/1-BP INS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs724159980 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs724159980;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=rs724159980" 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=rs724159980" 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=RCV000002233" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002233" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002233</a>
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<p><a href="#1" class="mim-tip-reference" title="Borck, G., Zarhrate, M., Cluzeau, C., Bal, E., Bonnefont, J.-P., Munnich, A., Cormier-Daire, V., Colleaux, L. <strong>Father-to-daughter transmission of Cornelia de Lange syndrome caused by a mutation in the 5-prime untranslated region of the NIPBL gene.</strong> Hum. Mutat. 27: 731-735, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16799922/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16799922</a>] [<a href="https://doi.org/10.1002/humu.20380" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16799922">Borck et al. (2006)</a> screened 21 patients with Cornelia de Lange syndrome (CDLS1; <a href="/entry/122470">122470</a>) with no previously identified NIPBL anomaly for mutations in the 5-prime untranslated region and the proximal promoter of the NIPBL gene. They identified a heterozygous deletion-insertion mutation in exon 1, 321 nucleotides upstream of the translation initiation codon (-321_-320delCCinsA) in an affected girl and her mildly affected father. The CC dinucleotide and the surrounding sequence are highly conserved in mammalian NIPBL homologs. The deletion-insertion variant was not identified in either parent of the father. The affected child was the first offspring of parents who were related as second cousins originating from Algeria. The diagnosis was made in the neonatal period because of characteristic dysmorphic facial features. The father had had feeding problems and gastroesophageal reflux in infancy, as did the proband. He also had developmental delay and speech delay, with his first words spoken at age 3 years, 6 months. At 7 years of age he was operated on for subvalvular aortic stenosis. He had growth retardation with a final height of 152 cm. The heights of his father and mother were 168 cm and 152 cm, respectively. Dysmorphic features in the father included arched eyebrows with synophrys, long eyelashes, long nose, and thin upper lip. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16799922" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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Borck, G., Zarhrate, M., Cluzeau, C., Bal, E., Bonnefont, J.-P., Munnich, A., Cormier-Daire, V., Colleaux, L.
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<strong>Father-to-daughter transmission of Cornelia de Lange syndrome caused by a mutation in the 5-prime untranslated region of the NIPBL gene.</strong>
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Hum. Mutat. 27: 731-735, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16799922/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16799922</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16799922" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.20380" target="_blank">Full Text</a>]
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D'Alessandro, L. C. A., Al Turki, S., Manickaraj, A. K., Manase, D., Mulder, B. J. M., Bergin, L., Rosenberg, H. C., Mondal, T., Gordon, E., Lougheed, J., Smythe, J., Devriendt, K., UK10K Consortium, Bhattacharya, S., Watkins, H., Bentham, J., Bowdin, S., Hurles, M. E., Mital, S.
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<strong>Exome sequencing identifies rare variants in multiple genes in atrioventricular septal defect.</strong>
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Genet. Med. 18: 189-198, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25996639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25996639</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25996639" 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/gim.2015.60" target="_blank">Full Text</a>]
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<a id="Davidson2019" class="mim-anchor"></a>
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Davidson, I. F., Bauer, B., Goetz, D., Tang, W., Wutz, G., Peters, J. M.
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<strong>DNA loop extrusion by human cohesin.</strong>
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Science 366: 1338-1345, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31753851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31753851</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31753851" 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/10.1126/science.aaz3418" target="_blank">Full Text</a>]
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<a id="Gillis2004" class="mim-anchor"></a>
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Gillis, L. A., McCallum, J., Kaur, M., DeScipio, C., Yaeger, D., Mariani, A., Kline, A. D., Li, H., Devoto, M., Jackson, L. G., Krantz, I. D.
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<strong>NIPBL mutational analysis in 120 individuals with Cornelia de Lange syndrome and evaluation of genotype-phenotype correlations.</strong>
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Am. J. Hum. Genet. 75: 610-623, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15318302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15318302</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15318302[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=15318302" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/424698" target="_blank">Full Text</a>]
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Kagey, M. H., Newman, J. J., Bilodeau, S., Zhan, Y., Orlando, D. A., van Berkum, N. L., Ebmeier, C. C., Goossens, J., Rahl, P. B., Levine, S. S., Taatjes, D. J., Dekker, J., Young, R. A.
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<strong>Mediator and cohesin connect gene expression and chromatin architecture.</strong>
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Nature 467: 430-435, 2010. Note: Erratum: Nature 472: 247 only, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20720539/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20720539</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20720539[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=20720539" 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/nature09380" target="_blank">Full Text</a>]
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Kaur, M., DeScipio, C., McCallum, J., Yaeger, D., Devoto, M., Jackson, L. G., Spinner, N. B., Krantz, I. D.
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<strong>Precocious sister chromatid separation (PSCS) in Cornelia de Lange syndrome.</strong>
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Am. J. Med. Genet. 138A: 27-31, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16100726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16100726</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16100726[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=16100726" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.30919" target="_blank">Full Text</a>]
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Kim, Y., Shi, Z., Zhang, H., Finkelstein, I. J., Yu, H.
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<strong>Human cohesin compacts DNA by loop extrusion.</strong>
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Science 366: 1345-1349, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31780627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31780627</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31780627" 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/10.1126/science.aaz4475" target="_blank">Full Text</a>]
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Krajewska-Walasek, M., Chrzanowska, K., Tylki-Szymanska, A., Bialecka, M.
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<strong>A further report of Brachmann-de Lange syndrome in two sibs with normal parents.</strong>
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Clin. Genet. 47: 324-327, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7554368/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7554368</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7554368" 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/10.1111/j.1399-0004.1995.tb03974.x" target="_blank">Full Text</a>]
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Krantz, I. D., McCallum, J., DeScipio, C., Kaur, M., Gillis, L. A., Yaeger, D., Jukofsky, L., Wasserman, N., Bottani, A., Morris, C. A., Nowaczyk, M. J. M., Toriello, H., and 9 others.
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<strong>Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B.</strong>
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Nature Genet. 36: 631-635, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146186</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15146186[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=15146186" 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/ng1364" target="_blank">Full Text</a>]
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Krantz, I. D., Tonkin, E., Smith, M., Devoto, M., Bottani, A., Simpson, C., Hofreiter, M., Abraham, V., Jukofsky, L., Conti, B. P., Strachan, T., Jackson, L.
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<strong>Exclusion of linkage to the CDL1 gene region on chromosome 3q26.3 in some familial cases of Cornelia de Lange syndrome.</strong>
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Am. J. Med. Genet. 101: 120-129, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11391654/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11391654</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11391654[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=11391654" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Lopez-Serra2014" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Lopez-Serra, L., Kelly, G., Patel, H., Stewart, A., Uhlmann, F.
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|
<strong>The Scc2-Scc4 complex acts in sister chromatid cohesion and transcriptional regulation by maintaining nucleosome-free regions.</strong>
|
|
Nature Genet. 46: 1147-1151, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25173104/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25173104</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25173104[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=25173104" 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.3080" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Rollins2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Rollins, R. A., Korom, M., Aulner, N., Martens, A., Dorsett, D.
|
|
<strong>Drosophila Nipped-B protein supports sister chromatid cohesion and opposes the Stromalin/Scc3 cohesion factor to facilitate long-range activation of the cut gene.</strong>
|
|
Molec. Cell. Biol. 24: 3100-3111, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15060134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15060134</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15060134[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=15060134" 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.24.8.3100-3111.2004" target="_blank">Full Text</a>]
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</p>
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<a id="13" class="mim-anchor"></a>
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<a id="Schwarzer2017" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Schwarzer, W., Abdennur, N., Goloborodko, A., Pekowska, A., Fudenberg, G., Loe-Mie, Y., Fonseca, N. A., Huber, W., Haering, C. H., Mirny, L., Spitz, F.
|
|
<strong>Two independent modes of chromatin organization revealed by cohesin removal.</strong>
|
|
Nature 551: 51-56, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29094699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29094699</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29094699[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=29094699" 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/nature24281" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="Seitan2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Seitan, V. C., Banks, P., Laval, S., Majid, N. A., Dorsett, D., Rana, A., Smith, J., Bateman, A., Krpic, S., Hostert, A., Rollins, R. A., Erdjument-Bromage, H., Tempst, P., Benard, C. Y., Hekimi, S., Newbury, S. F., Strachan, T.
|
|
<strong>Metazoan Scc4 homologs link sister chromatid cohesion to cell and axon migration guidance.</strong>
|
|
PLoS Biol. 4: e242, 2006. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16802858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16802858</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16802858" 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/10.1371/journal.pbio.0040242" target="_blank">Full Text</a>]
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<li>
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<a id="15" class="mim-anchor"></a>
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<a id="Shi2020" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Shi, Z., Gao, H., Bai, X., Yu, H.
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<strong>Cryo-EM structure of the human cohesin-NIPBL-DNA complex.</strong>
|
|
Science 368: 1454-1459, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32409525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32409525</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32409525" 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/10.1126/science.abb0981" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="16" class="mim-anchor"></a>
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<a id="Tonkin2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tonkin, E. T., Wang, T.-J., Lisgo, S., Bamshad, M. J., Strachan, T.
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|
<strong>NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.</strong>
|
|
Nature Genet. 36: 636-641, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146185</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15146185" 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/ng1363" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="17" class="mim-anchor"></a>
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<a id="Watrin2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Watrin, E., Schleiffer, A., Tanaka, K., Eisenhaber, F., Nasmyth, K., Peters, J.-M.
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<strong>Human Scc4 is required for cohesin binding to chromatin, sister-chromatid cohesion, and mitotic progression.</strong>
|
|
Curr. Biol. 16: 863-874, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16682347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16682347</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16682347" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.cub.2006.03.049" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="18" class="mim-anchor"></a>
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<a id="Yan2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yan, J., Saifi, G. M., Wierzba, T. H., Withers, M., Bien-Willner, G. A., Limon, J., Stankiewicz, P., Lupski, J. R., Wierzba, J.
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<strong>Mutational and genotype-phenotype correlation analyses in 28 Polish patients with Cornelia de Lange syndrome.</strong>
|
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Am. J. Med. Genet. 140A: 1531-1541, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16770807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16770807</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16770807" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.31305" target="_blank">Full Text</a>]
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</ol>
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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="contributors" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 10/20/2020
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 05/06/2020<br>Ada Hamosh - updated : 02/02/2018<br>Ada Hamosh - updated : 12/11/2017<br>Patricia A. Hartz - updated : 10/17/2014<br>Patricia A. Hartz - updated : 3/19/2012<br>Ada Hamosh - updated : 10/7/2010<br>Cassandra L. Kniffin - updated : 8/18/2006<br>Cassandra L. Kniffin - updated : 9/19/2005<br>Victor A. McKusick - updated : 9/14/2004
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 5/19/2004
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 07/07/2023
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</span>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 10/22/2020<br>mgross : 10/20/2020<br>alopez : 05/06/2020<br>alopez : 05/06/2020<br>alopez : 02/02/2018<br>alopez : 12/11/2017<br>mgross : 10/20/2014<br>mgross : 10/20/2014<br>mcolton : 10/17/2014<br>carol : 9/19/2013<br>mgross : 3/28/2012<br>terry : 3/19/2012<br>alopez : 6/10/2011<br>alopez : 10/8/2010<br>terry : 10/7/2010<br>alopez : 2/13/2007<br>alopez : 9/5/2006<br>wwang : 8/25/2006<br>ckniffin : 8/18/2006<br>carol : 10/5/2005<br>wwang : 10/3/2005<br>ckniffin : 9/19/2005<br>tkritzer : 9/21/2004<br>tkritzer : 9/14/2004<br>terry : 9/14/2004<br>alopez : 5/28/2004<br>alopez : 5/25/2004<br>alopez : 5/19/2004
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 608667
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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NIPPED-B-LIKE; NIPBL
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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NIPPED-B, DROSOPHILA, HOMOLOG OF<br />
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DELANGIN<br />
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SISTER CHROMATID COHESION 2, S. CEREVISIAE, HOMOLOG OF; SCC2
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: NIPBL</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 5p13.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 5:36,876,769-37,066,413 </span>
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</em>
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</strong>
|
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
|
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</th>
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<th>
|
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
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5p13.2
|
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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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Cornelia de Lange syndrome 1
|
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
122470
|
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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Autosomal dominant
|
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
3
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Sister chromatids remain connected following duplication in S phase until they segregate during anaphase of mitosis or meiosis II. This cohesion counteracts the force of spindle microtubules on sister kinetochores and allows chromosomes to align at the mitotic spindle. Sister chromatid cohesion is also essential for segregation of homologous chromosomes during meiosis I and for repair of DNA double-strand breaks during G2 phase. Cohesin (see 606462) is a protein complex required for sister chromatid cohesion. NIPBL forms a dimer with MAU2 (614560) that is essential for loading the cohesin complex onto sister chromatids (Watrin et al., 2006). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In the course of searching for the molecular basis of Cornelia de Lange syndrome (CDLS1; 122470), Tonkin et al. (2004) and Krantz et al. (2004) analyzed de novo balanced translocations associated with Cornelia de Lange syndrome and identified a novel gene at 5p13.1 that is disrupted in these cases. Tonkin et al. (2004) designated the product of the Nipped-B-like (NIPBL) gene 'delangin.' The coding sequence commences in exon 2 and continues either to exon 47, generating a long isoform (2,804 amino acids), or to an expanded variant of exon 46, generating a slightly shorter isoform (2,697 amino acids). Residues 1 through 2,683 of the short and long isoforms are identical; the short isoform contains a 14-amino acid C-terminal end that is unrelated to the 121-amino acid C-terminal end of the long isoform (Tonkin et al., 2004). Northern blot analysis showed that NIPBL is strongly expressed in fetal and adult kidney, fetal liver, adult placenta, heart, skeletal muscle, and thymus, but weakly or almost undetectably expressed in fetal and adult brain and lung and in adult liver, colon, small intestine, and leukocytes (Tonkin et al., 2004). Tonkin et al. (2004) found that vertebrate delangins have substantial homology to orthologs in flies, worms, plants, and fungi, including Scc2-type sister chromatid cohesion proteins, and D. melanogaster Nipped-B. </p><p>Using bioinformatic analysis, Yan et al. (2006) showed that NIPBL protein contains an N-terminal caldesmon (CALD1; 114213) domain, a calponin (CNN1; 600806) domain, and 2 calmodulin (CALM1; 114180)-binding motifs, followed by a nuclear localization signal, a nuclear export signal, 5 HEAT repeats, and a C-terminal DNA-binding domain. </p>
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</span>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The NIPBL gene contains 47 exons spanning 188 kb, with commencement of the coding sequence in exon 2 (Krantz et al., 2004; Tonkin et al., 2004). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Krantz et al. (2004) and Tonkin et al. (2004) identified the NIPBL gene within chromosome 5p13. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In situ hybridization to whole mouse embryos detected Nipbl transcripts at gestation days 9.5 and 10.5, with notable accumulations in limb bud, branchial arch, and craniofacial mesenchyme (Krantz et al., 2004). In situ hybridization to human embryonic tissue sections revealed an expression pattern largely consistent with the CDLS phenotype (Tonkin et al., 2004). Krantz et al. (2004) found evidence for alternative splicing of the NIPBL gene in the presence of multiple transcripts detected on Northern blot analysis. </p><p>The evolution of an ancestral sister chromatid cohesion protein to acquire an additional role in developmental gene regulation suggested to Tonkin et al. (2004) that there are parallels between CDLS and Roberts syndrome (268300), which is characterized by growth retardation, limb reduction defects, craniofacial abnormalities, and premature centromere separation. A dual role for Nipped-B in sister chromatid cohesion and developmental regulation was confirmed by Rollins et al. (2004). </p><p>By metaphase spread analysis, Kaur et al. (2005) found evidence of precocious sister chromatid separation (PSCS) in 37 (41%) of 90 probands with CDLS compared to 8 (9%) of controls. Of the 37 CDLS patients with PSCS, 16 (43%) had mutations in the NIPBL gene, whereas 21 (57%) did not. Both severe and mild phenotypes were seen in those with PSCS and those without PSCS. Kaur et al. (2005) noted that Roberts syndrome (268300), which has phenotypic overlap with CDLS and is associated with premature sister chromatid separation, is caused by mutations in the ESCO2 gene (609353), which is required for proper establishment of the sister chromatid cohesion complex. </p><p>Using immunoprecipitation analysis, Watrin et al. (2006) showed that SCC4 (MAU2; 614560) interacted with SCC2 in HeLa cell nucleoplasmic extracts. SCC4 and SCC2 cosedimented in fractionated HeLa cell extracts and colocalized on chromatin in HeLa cells during interphase and telophase. Depletion of either SCC4 or SCC2 via small interfering RNA delayed mitotic exit and caused loss of cohesin from chromatin during interphase and telophase, precocious loss of sister chromatid cohesion, misalignment of chromosomes, appearance of single sister chromatids, and prometaphase arrest. Knockdown of either SCC4 or SCC2 also reduced the amount of the other protein, suggesting that physical association between them is required for stability. Chromosomes in SCC4- or SCC2-depleted cells lacked cohesin despite the presence of the cohesin protectors SGO1 (SGOL1; 609168) and BUB1 (602452). </p><p>Independently, Seitan et al. (2006) showed that MAU2 coimmunoprecipitated with delangin. Drosophila and Xenopus orthologs of MAU2 and delangin also interacted directly. Protein truncation and yeast 2-hybrid analyses revealed that the N termini of MAU2 and delangin mediated their interaction. Knockdown of MAU2 in HeLa cells resulted in increased frequency of precocious sister chromatid separation. In control cells, release from block in G2/M resulted in rapid loading of cohesin subunits onto chromatin. In MAU2 knockdown cells, cohesin complexes formed, but they failed to load onto chromatin. </p><p>Kagey et al. (2010) reported that Mediator (see MED8, 607956) and cohesin (see SMC1, 300040) physically and functionally connect the enhancers and core promoters of active genes in murine embryonic stem cells. Mediator, a transcriptional coactivator, forms a complex with cohesin, which can form rings that connect 2 DNA segments. The cohesin-loading factor NIPBL is associated with Mediator-cohesin complexes, providing a means to load cohesin at promoters. DNA looping is observed between the enhancers and promoters occupied by Mediator and cohesin. Mediator and cohesin co-occupy different promoters in different cells, thus generating cell type-specific DNA loops linked to the gene expression program of each cell. </p><p>In yeast, Lopez-Serra et al. (2014) found that the RSC chromatin-remodeling complex recruited Scc2-Scc4 dimers to broad, shallow nucleosome-free regions. Here, Scc2-Scc4 maintained the accessible DNA for the subsequent cohesin-loading reaction. </p><p>Schwarzer et al. (2017) found that deletion of the cohesin-loading factor Nipbl in mouse liver led to a marked reorganization of chromosomal folding. Topologically associating domains (TADs) and associated chromosome conformation capture (Hi-C) peaks vanished globally, even in the absence of transcriptional changes. By contrast, compartmental segregation was preserved and even reinforced. Strikingly, the disappearance of TADs unmasked a finer compartment structure that accurately reflects the underlying epigenetic landscape. These observations demonstrated that the 3-dimensional organization of the genome results from the interplay of 2 independent mechanisms: cohesin-independent segregation of the genome into fine-scale compartments, defined by chromatin state, and cohesin-dependent formation of TADs, possibly by loop extrusion, which helps to guide distant enhancers to their target genes. </p><p>Using biochemical reconstitution, Davidson et al. (2019) found that single human cohesin complexes form DNA loops symmetrically at rates up to 2.1 kilobase pairs per second. Loop formation and maintenance depend on cohesin's ATPase activity and on NIPBL-MAU2 (614560), but not on topologic entrapment of DNA by cohesin (components include SMC3, 606062; SMC1A, 300040; STAG1, 604358; STAG2, 300826). During loop formation, cohesin and NIPBL-MAU2 reside at the base of loops, which indicates that they generate loops by extrusion. Davidson et al. (2019) concluded that their results showed that cohesin and NIPBL-MAU2 form an active holoenzyme that interacts with DNA either pseudotopologically or nontopologically to extrude genomic interphase DNA into loops. </p><p>Kim et al. (2019) independently used single-molecule imaging to show that the recombinant human cohesin-NIPBL complex compacts both naked and nucleosome-bound DNA by extruding DNA loops. DNA compaction by cohesin requires ATP hydrolysis and is force-sensitive. This compaction is processive over tens of kilobases at an average rate of 0.5 kilobases per second. Compaction of double-tethered DNA suggests that a cohesin dimer extrudes DNA loops bidirectionally. Kim et al. (2019) concluded that their results established cohesin-NIPBL as an ATP-driven molecular machine capable of loop extrusion. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Biochemical Features</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using cryoelectron microscopy, Shi et al. (2020) determined the structure of human cohesin bound to the C-terminal HEAT domain of NIPBL and DNA at medium resolution. Cohesin and NIPBL interacted extensively and formed a central tunnel to entrap a 72-bp DNA. NIPBL and DNA promoted engagement of the ATPase head domains of cohesin and ATP binding. The hinge domains of cohesin adopted an 'open washer' conformation and docked onto the STAG1 subunit. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Tonkin et al. (2004) studied CDLS cases without translocations and identified 9 plausible point mutations in the NIPBL gene, at least 5 of which arose de novo. As they found NIPBL mutations in individuals with severe and mild Cornelia de Lange syndrome-1 (CDLS1; 122470), phenotypic variation may be explained in part by allelic heterogeneity. The spectrum and distribution of mutations implied that pathogenesis arose from loss or altered function of a single NIPBL allele. The mutation detection rate in the study of Tonkin et al. (2004) was approximately 50%. Thus, locus heterogeneity as well as allelic heterogeneity may be present, but limitations of the screening methods were also cited as a plausible explanation for the comparatively low mutation detection rate. On the other hand, considerable intrafamilial variation in phenotype of CDLS, even between affected sibs (Krajewska-Walasek et al., 1995), suggests that additional factors may be important. Tonkin et al. (2004) proposed that perturbed delangin function may inappropriately activate distal-less homeobox (DLX) genes, thereby contributing to the proximodistal limb patterning defects in CDLS. </p><p>Krantz et al. (2004) identified 6 point mutations in individuals with CDLS (608667.0001-608667.0006). All were expected to result in a truncated or, in the case of the met1-to-lys mutation (M1K; 608667.0001), an untranslated protein. </p><p>Gillis et al. (2004) described the spectrum and distribution of NIPBL mutations in a large well-characterized cohort of individuals with CDLS. In 56 (47%) of 120 unrelated individuals with sporadic or familial CDLS, they identified mutations in the NIPBL gene (see 608667.0007-608667.0012). In 49 (46%) of the 106 individuals with sporadic CDLS, 44 different mutations were identified, 14 (32%) of which were small deletions. In 6 the 7 familial cases of CDLS in which NIPBL mutations were identified, germline mosaicism was considered the likely mechanism for the occurrence of affected sibs with mutation-negative parents. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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D'Alessandro et al. (2016) performed whole-exome sequencing in 81 unrelated probands with atrioventricular septal defect (AVSD) to identify potential causal variants in a comprehensive set of 112 genes with strong biological relevance to AVSD. A significant enrichment of rare and rare damaging variants was identified in the gene set, compared with controls (odds ratio (OR) 1.52; 95% confidence interval (CI), 1.35-1.71; p = 4.8 x 10(-11)). The enrichment was specific to AVSD probands, compared with a cohort without AVSD with tetralogy of Fallot (OR 2.25; 95% CI, 1.84-2.76; p = 2.2 x 10(-16)). Six genes, including the syndrome-associated gene NIPBL, were enriched for rare variants in AVSD. The findings were confirmed in a replication cohort of 81 AVSD probands. D'Alessandro et al. (2016) concluded that mutations in genes with strong biological relevance to AVSD, including syndrome-associated genes, can contribute to AVSD, even in those with isolated heart disease. Six AVSD probands (7.4%) had rare nonsynonymous variants in NIPBL compared with 2.3% in Exome Variant Server (EVS) controls (OR 3.3; p = 0.02). Two novel variants (M1318V and S2471T) involved highly conserved residues and were predicted to be damaging. Two variants (N105D and N393K) each previously occurred in a single individual among 4,300 EVS European American controls and not in other control data sets. None of the AVSD probands with NIPBL variants had clinical characteristics of CDLS. Two probands had associated semilunar valve anomalies, which are commonly associated with CDLS. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Genotype/Phenotype Correlations</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Gillis et al. (2004) found statistically significant phenotypic differences between NIPBL mutation-positive and NIPBL-negative individuals with CDLS. Analysis also suggested a trend toward a milder phenotype in individuals with missense mutations. </p><p>Yan et al. (2006) identified 13 different NIPBL mutations, including 11 novel mutations, in 13 (46%) of 28 Polish patients with a clinical diagnosis of CDLS. Eleven of the mutations resulted in a premature termination of the protein. Mutation-positive patients were more severely affected than mutation-negative patients with respect to prenatal growth, facial dysmorphism, and speech impairment. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>13 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 CORNELIA DE LANGE SYNDROME 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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NIPBL, MET1LYS
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<br />
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SNP: rs121918264,
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ClinVar: RCV000002221, RCV004700178
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 3 sibs with Cornelia de Lange syndrome (CDLS1; 122470), each with a different father, Krantz et al. (2004) identified a start codon mutation, 2G-A (M1K), in the NIPBL gene. The mutation was not present in their mother or in the 2 fathers from whom samples were available. All 3 sibs, aged 17, 8, and 3 years, had moderate growth and cognitive delays, small hands without reduction defects, hirsutism, and typical facial features. Germline mosaicism was presumably the mechanism for the familial recurrence since the mother had not manifested features of the disorder. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 CORNELIA DE LANGE SYNDROME 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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NIPBL, TYR2430CYS
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<br />
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SNP: rs121918265,
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ClinVar: RCV000002222
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In an individual with classic features of Cornelia de Lange syndrome (CDLS1; 122470), Tonkin et al. (2004) identified a 7289A-G transition in exon 43 of the NIPBL gene resulting in a tyr2430-to-cys (Y2430C) amino acid change in the delangin protein. The patient showed severe growth retardation, lobster limb defect, characteristic face, feeding difficulties, and gastroesophageal reflux. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 CORNELIA DE LANGE SYNDROME 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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NIPBL, 1-BP DEL, 150G
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<br />
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SNP: rs1554011042,
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ClinVar: RCV000002223
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a child with Cornelia de Lange syndrome (CDLS1; 122470), Krantz et al. (2004) identified a 1-bp deletion, 150delG, in exon 3 of the NIPBL gene, resulting in frameshift with a stop codon 28 amino acids downstream. The male child, seen at 4.5 months of age, had severe bilateral upper limb reduction defects (oligodactyly, single digit), severe growth and cognitive delays, typical facial features, hirsutism, and cleft palate. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 CORNELIA DE LANGE SYNDROME 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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NIPBL, 1-BP INS, 7306G
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<br />
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SNP: rs1561222491,
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ClinVar: RCV000002224
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with classic features of Cornelia de Lange syndrome (CDLS1; 122470), Tonkin et al. (2004) found a de novo 1-bp insertion, 7306_7307insG, in exon 43 of the NIPBL gene. The patient showed growth retardation, microbrachycephaly, long philtrum, thin lips, crescent-shaped mouth, synophrys, bushy eyebrows, general hirsutism, hearing impairment, myopia, micromelia, clinodactyly, proximally placed thumbs, fixed flexion of the elbows, syndactyly of the feet, bilateral inguinal hernias, and undescended testes. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0005 CORNELIA DE LANGE SYNDROME 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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NIPBL, 1-BP INS, 1546G
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<br />
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SNP: rs1554016981,
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ClinVar: RCV000002225
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In an adult female with classic features of Cornelia de Lange syndrome (CDLS1; 122470), Krantz et al. (2004) identified a 1-bp insertion, 1546_1547insG, in exon 10 of the NIPBL gene. The insertion resulted in a frameshift with a stop codon 3 amino acids downstream. The patient showed severe growth and cognitive delays, reduction defect of the right limb (oligodactyly, 4 digits) and small left hand with no reduction defect, typical facial features, hirsutism, cleft palate, and hearing loss. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0006 CORNELIA DE LANGE SYNDROME 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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NIPBL, ILE1206DEL
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<br />
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SNP: rs121918266,
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ClinVar: RCV000002226
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with mild features of Cornelia de Lange syndrome (CDLS1; 122470), Tonkin et al. (2004) described a 3-bp deletion of nucleotides 3616 through 3618 in exon 14 of the NIPBL gene (ATA) resulting in deletion of isoleucine-1206. The change was absent in maternal DNA; no paternal DNA was available. The patient showed growth retardation, small hands, microcephaly, speech delay, and inguinal hernia. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0007 CORNELIA DE LANGE SYNDROME 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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NIPBL, 2-BP DEL, 2479AG
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<br />
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SNP: rs398124465,
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ClinVar: RCV000082485, RCV000146547
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 unrelated children with sporadic Cornelia de Lange syndrome (CDLS1; 122470), Gillis et al. (2004) identified a 2-bp deletion in exon 10 of the NIPBL gene, 2479delAG, resulting in a frameshift and truncation of the protein 2 amino acids downstream. Both children were severely affected in terms of growth and development; however, one had significant limb reduction defects whereas the other did not. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0008 CORNELIA DE LANGE SYNDROME 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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NIPBL, ARG1723TER
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<br />
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SNP: rs121918267,
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ClinVar: RCV000002228
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 affected brothers from a family with Cornelia de Lange syndrome (CDLS1; 122470), previously reported by Krantz et al. (2004), Gillis et al. (2004) identified an arg1723-to-ter (R1723X) substitution in exon 26 of the NIPBL gene. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0009 CORNELIA DE LANGE SYNDROME 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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NIPBL, ALA1246GLY
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<br />
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SNP: rs121918268,
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ClinVar: RCV000002229
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Krantz et al. (2001) described male first cousins from a family with Cornelia de Lange syndrome (CDLS1; 122470), the sons of unaffected sisters, who were excluded from linkage analysis because of the atypical inheritance pattern. In the 2 affected males, Gillis et al. (2004) identified different de novo mutations in the NIPBL gene, neither of which was present in the parents: in one, an ala1246-to-gly (A1246G) substitution in exon 15, and in the other, a 7861G-C transversion at position -1 in the intron upstream of exon 46 (608667.0010). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0010 CORNELIA DE LANGE SYNDROME 1</strong>
|
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</span>
|
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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NIPBL, IVS45AS, G-C, -1
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<br />
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SNP: rs1561231553,
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ClinVar: RCV000002230
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>For discussion of the de novo 7861G-C transversion at position -1 in the intron upstream of exon 46 in the NIPBL gene that was found in compound heterozygous state in a patient with Cornelia de Lange syndrome-1 (CDLS1; 122470) by Gillis et al. (2004), see 608667.0009. </p>
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|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 CORNELIA DE LANGE SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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NIPBL, IVS44DS, A-G, +4
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<br />
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ClinVar: RCV000002231
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with Cornelia de Lange syndrome (CDLS1; 122470), previously described by Krantz et al. (2004), Gillis et al. (2004) identified a 7321A-G transition at position +4 of exon 43 of the NIPBL gene. The mutation was identified in 2 of 4 affected sibs from whom samples were available, as well as in the mildly affected mother. </p>
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|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 CORNELIA DE LANGE SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
NIPBL, ARG1536TER
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<br />
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SNP: rs121918269,
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|
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ClinVar: RCV000002232
|
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</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 unrelated patients with sporadic Cornelia de Lange syndrome (CDLS1; 122470), Gillis et al. (2004) identified an arg1536-to-ter (R1536X) substitution in exon 22 of the NIPBL gene. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 CORNELIA DE LANGE SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NIPBL, 2-BP DEL/1-BP INS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs724159980,
|
|
|
|
|
|
|
|
ClinVar: RCV000002233
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Borck et al. (2006) screened 21 patients with Cornelia de Lange syndrome (CDLS1; 122470) with no previously identified NIPBL anomaly for mutations in the 5-prime untranslated region and the proximal promoter of the NIPBL gene. They identified a heterozygous deletion-insertion mutation in exon 1, 321 nucleotides upstream of the translation initiation codon (-321_-320delCCinsA) in an affected girl and her mildly affected father. The CC dinucleotide and the surrounding sequence are highly conserved in mammalian NIPBL homologs. The deletion-insertion variant was not identified in either parent of the father. The affected child was the first offspring of parents who were related as second cousins originating from Algeria. The diagnosis was made in the neonatal period because of characteristic dysmorphic facial features. The father had had feeding problems and gastroesophageal reflux in infancy, as did the proband. He also had developmental delay and speech delay, with his first words spoken at age 3 years, 6 months. At 7 years of age he was operated on for subvalvular aortic stenosis. He had growth retardation with a final height of 152 cm. The heights of his father and mother were 168 cm and 152 cm, respectively. Dysmorphic features in the father included arched eyebrows with synophrys, long eyelashes, long nose, and thin upper lip. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
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|
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</div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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<div>
|
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<ol>
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<li>
|
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<p class="mim-text-font">
|
|
Borck, G., Zarhrate, M., Cluzeau, C., Bal, E., Bonnefont, J.-P., Munnich, A., Cormier-Daire, V., Colleaux, L.
|
|
<strong>Father-to-daughter transmission of Cornelia de Lange syndrome caused by a mutation in the 5-prime untranslated region of the NIPBL gene.</strong>
|
|
Hum. Mutat. 27: 731-735, 2006.
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[PubMed: 16799922]
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[Full Text: https://doi.org/10.1002/humu.20380]
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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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D'Alessandro, L. C. A., Al Turki, S., Manickaraj, A. K., Manase, D., Mulder, B. J. M., Bergin, L., Rosenberg, H. C., Mondal, T., Gordon, E., Lougheed, J., Smythe, J., Devriendt, K., UK10K Consortium, Bhattacharya, S., Watkins, H., Bentham, J., Bowdin, S., Hurles, M. E., Mital, S.
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<strong>Exome sequencing identifies rare variants in multiple genes in atrioventricular septal defect.</strong>
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Genet. Med. 18: 189-198, 2016.
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[PubMed: 25996639]
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[Full Text: https://doi.org/10.1038/gim.2015.60]
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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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Davidson, I. F., Bauer, B., Goetz, D., Tang, W., Wutz, G., Peters, J. M.
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<strong>DNA loop extrusion by human cohesin.</strong>
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Science 366: 1338-1345, 2019.
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[PubMed: 31753851]
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[Full Text: https://doi.org/10.1126/science.aaz3418]
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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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Gillis, L. A., McCallum, J., Kaur, M., DeScipio, C., Yaeger, D., Mariani, A., Kline, A. D., Li, H., Devoto, M., Jackson, L. G., Krantz, I. D.
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<strong>NIPBL mutational analysis in 120 individuals with Cornelia de Lange syndrome and evaluation of genotype-phenotype correlations.</strong>
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Am. J. Hum. Genet. 75: 610-623, 2004.
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[PubMed: 15318302]
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[Full Text: https://doi.org/10.1086/424698]
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<p class="mim-text-font">
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Kagey, M. H., Newman, J. J., Bilodeau, S., Zhan, Y., Orlando, D. A., van Berkum, N. L., Ebmeier, C. C., Goossens, J., Rahl, P. B., Levine, S. S., Taatjes, D. J., Dekker, J., Young, R. A.
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<strong>Mediator and cohesin connect gene expression and chromatin architecture.</strong>
|
|
Nature 467: 430-435, 2010. Note: Erratum: Nature 472: 247 only, 2011.
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[PubMed: 20720539]
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[Full Text: https://doi.org/10.1038/nature09380]
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<li>
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<p class="mim-text-font">
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Kaur, M., DeScipio, C., McCallum, J., Yaeger, D., Devoto, M., Jackson, L. G., Spinner, N. B., Krantz, I. D.
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<strong>Precocious sister chromatid separation (PSCS) in Cornelia de Lange syndrome.</strong>
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Am. J. Med. Genet. 138A: 27-31, 2005.
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[PubMed: 16100726]
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[Full Text: https://doi.org/10.1002/ajmg.a.30919]
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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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Kim, Y., Shi, Z., Zhang, H., Finkelstein, I. J., Yu, H.
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<strong>Human cohesin compacts DNA by loop extrusion.</strong>
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Science 366: 1345-1349, 2019.
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[PubMed: 31780627]
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[Full Text: https://doi.org/10.1126/science.aaz4475]
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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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Krajewska-Walasek, M., Chrzanowska, K., Tylki-Szymanska, A., Bialecka, M.
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<strong>A further report of Brachmann-de Lange syndrome in two sibs with normal parents.</strong>
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Clin. Genet. 47: 324-327, 1995.
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[PubMed: 7554368]
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[Full Text: https://doi.org/10.1111/j.1399-0004.1995.tb03974.x]
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</p>
|
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</li>
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<li>
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<p class="mim-text-font">
|
|
Krantz, I. D., McCallum, J., DeScipio, C., Kaur, M., Gillis, L. A., Yaeger, D., Jukofsky, L., Wasserman, N., Bottani, A., Morris, C. A., Nowaczyk, M. J. M., Toriello, H., and 9 others.
|
|
<strong>Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B.</strong>
|
|
Nature Genet. 36: 631-635, 2004.
|
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|
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|
|
[PubMed: 15146186]
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[Full Text: https://doi.org/10.1038/ng1364]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Krantz, I. D., Tonkin, E., Smith, M., Devoto, M., Bottani, A., Simpson, C., Hofreiter, M., Abraham, V., Jukofsky, L., Conti, B. P., Strachan, T., Jackson, L.
|
|
<strong>Exclusion of linkage to the CDL1 gene region on chromosome 3q26.3 in some familial cases of Cornelia de Lange syndrome.</strong>
|
|
Am. J. Med. Genet. 101: 120-129, 2001.
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|
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[PubMed: 11391654]
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|
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|
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Lopez-Serra, L., Kelly, G., Patel, H., Stewart, A., Uhlmann, F.
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<strong>The Scc2-Scc4 complex acts in sister chromatid cohesion and transcriptional regulation by maintaining nucleosome-free regions.</strong>
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Nature Genet. 46: 1147-1151, 2014.
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[PubMed: 25173104]
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[Full Text: https://doi.org/10.1038/ng.3080]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Rollins, R. A., Korom, M., Aulner, N., Martens, A., Dorsett, D.
|
|
<strong>Drosophila Nipped-B protein supports sister chromatid cohesion and opposes the Stromalin/Scc3 cohesion factor to facilitate long-range activation of the cut gene.</strong>
|
|
Molec. Cell. Biol. 24: 3100-3111, 2004.
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|
|
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|
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[PubMed: 15060134]
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[Full Text: https://doi.org/10.1128/MCB.24.8.3100-3111.2004]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Schwarzer, W., Abdennur, N., Goloborodko, A., Pekowska, A., Fudenberg, G., Loe-Mie, Y., Fonseca, N. A., Huber, W., Haering, C. H., Mirny, L., Spitz, F.
|
|
<strong>Two independent modes of chromatin organization revealed by cohesin removal.</strong>
|
|
Nature 551: 51-56, 2017.
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|
|
|
[PubMed: 29094699]
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|
|
[Full Text: https://doi.org/10.1038/nature24281]
|
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Seitan, V. C., Banks, P., Laval, S., Majid, N. A., Dorsett, D., Rana, A., Smith, J., Bateman, A., Krpic, S., Hostert, A., Rollins, R. A., Erdjument-Bromage, H., Tempst, P., Benard, C. Y., Hekimi, S., Newbury, S. F., Strachan, T.
|
|
<strong>Metazoan Scc4 homologs link sister chromatid cohesion to cell and axon migration guidance.</strong>
|
|
PLoS Biol. 4: e242, 2006. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 16802858]
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[Full Text: https://doi.org/10.1371/journal.pbio.0040242]
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Shi, Z., Gao, H., Bai, X., Yu, H.
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<strong>Cryo-EM structure of the human cohesin-NIPBL-DNA complex.</strong>
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Tonkin, E. T., Wang, T.-J., Lisgo, S., Bamshad, M. J., Strachan, T.
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<strong>NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.</strong>
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Watrin, E., Schleiffer, A., Tanaka, K., Eisenhaber, F., Nasmyth, K., Peters, J.-M.
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<strong>Human Scc4 is required for cohesin binding to chromatin, sister-chromatid cohesion, and mitotic progression.</strong>
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Yan, J., Saifi, G. M., Wierzba, T. H., Withers, M., Bien-Willner, G. A., Limon, J., Stankiewicz, P., Lupski, J. R., Wierzba, J.
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