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Entry
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- *610528 - CHROMODOMAIN HELICASE DNA-BINDING PROTEIN 8; CHD8
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*610528</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/610528">Table View</a>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div id="mimFloatingLinksMenu">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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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="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=ENSG00000100888;t=ENST00000646647" 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=57680" 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=610528" 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 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="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=ENSG00000100888;t=ENST00000646647" 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_001170629,NM_020920" 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_001170629" 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=610528" 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=16712&isoform_id=16712_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/CHD8" 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/19684009,21740345,22477368,34328020,34526499,39795273,40226549,49522741,51476360,71051301,114326455,119586789,282165704,317373586,444732925" 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/Q9HCK8" 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=57680" 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=ENSG00000100888;t=ENST00000646647" 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=CHD8" 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=CHD8" 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+57680" 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/CHD8" 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:57680" 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/57680" 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=chr14&hgg_gene=ENST00000646647.2&hgg_start=21385199&hgg_end=21456123&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 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:20153" 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:20153" 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/chd8" 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=610528[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=610528[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/CHD8/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/ENSG00000100888" 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=CHD8" 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=CHD8" 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=CHD8" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=CHD8&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/PA134957052" 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:20153" 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/FBgn0266557.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:1915022" 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/CHD8#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:1915022" 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/57680/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://omia.org/OMIA002658/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=57680" 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=WBGene00007053;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-030131-6320" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:57680" 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=CHD8&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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610528
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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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CHROMODOMAIN HELICASE DNA-BINDING PROTEIN 8; CHD8
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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AXIS DUPLICATION INHIBITOR; DUPLIN<br />
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KIAA1564
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
|
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=CHD8" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CHD8</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/14/54?start=-3&limit=10&highlight=54">14q11.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr14:21385199-21456123&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'})">14:21,385,199-21,456,123</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
|
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</th>
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<th>
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Phenotype
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</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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<a href="/geneMap/14/54?start=-3&limit=10&highlight=54">
|
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14q11.2
|
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</a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
Intellectual developmental disorder with autism and macrocephaly
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
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<a href="/entry/615032"> 615032 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/610528" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/610528" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
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</div>
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<p>CHD8 is an ATP-dependent chromatin-remodeling factor that regulates transcription of beta-catenin (CTNNB1; <a href="/entry/116806">116806</a>) target genes (<a href="#22" class="mim-tip-reference" title="Thompson, B. A., Tremblay, V., Lin, G., Bochar, D. A. <strong>CHD8 is an ATP-dependent chromatin remodeling factor that regulates beta-catenin target genes.</strong> Molec. Cell. Biol. 28: 3894-3904, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18378692/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18378692</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18378692[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.00322-08" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18378692">Thompson et al., 2008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18378692" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By sequencing clones from a size-fractionated fetal brain cDNA library, <a href="#12" class="mim-tip-reference" title="Nagase, T., Kikuno, R., Nakayama, M., Hirosawa, M., Ohara, O. <strong>Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</strong> DNA Res. 7: 273-281, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10997877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10997877</a>] [<a href="https://doi.org/10.1093/dnares/7.4.271" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10997877">Nagase et al. (2000)</a> cloned CHD8, which they designated KIAA1564. The deduced protein contains 1,417 amino acids. RT-PCR ELISA detected moderate expression in all adult and fetal tissues and specific brain regions examined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10997877" 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="#19" class="mim-tip-reference" title="Sakamoto, I., Kishida, S., Fukui, A., Kishida, M., Yamamoto, H., Hino, S., Michiue, T., Takada, S., Asashima, M., Kikuchi, A. <strong>A novel beta-catenin-binding protein inhibits beta-catenin-dependent Tcf activation and axis formation.</strong> J. Biol. Chem. 275: 32871-32878, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10921920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10921920</a>] [<a href="https://doi.org/10.1074/jbc.M004089200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10921920">Sakamoto et al. (2000)</a> cloned rat Chd8, which they called Duplin. The deduced 749-amino acid protein was expressed mainly in the nuclear fraction of transfected COS cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10921920" 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="Ishihara, K., Oshimura, M., Nakao, M. <strong>CTCF-dependent chromatin insulator is linked to epigenetic remodeling.</strong> Molec. Cell 23: 733-742, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16949368/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16949368</a>] [<a href="https://doi.org/10.1016/j.molcel.2006.08.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16949368">Ishihara et al. (2006)</a> cloned mouse Chd8. The deduced 2,582-amino acid protein has 2 chromodomains, followed by a central helicase/ATPase domain and 2 C-terminal BRK domains. Northern blot analysis detected ubiquitous Chd8 expression in mouse tissues, with highest levels in heart and testis. Western blot analysis of HeLa cells detected endogenous CHD8 at an apparent molecular mass of 240 kD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16949368" 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="#14" class="mim-tip-reference" title="Nishiyama, M., Nakayama, K., Tsunematsu, R., Tsukiyama, T., Kikuchi, A., Nakayama, K. I. <strong>Early embryonic death in mice lacking the beta-catenin-binding protein Duplin.</strong> Molec. Cell. Biol. 24: 8386-8394, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15367660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15367660</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15367660[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.24.19.8386-8394.2004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15367660">Nishiyama et al. (2004)</a> determined that the mouse Chd8 gene contains 9 exons and spans about 13 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15367660" 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 transient transfection assays in HEK293 cells, <a href="#9" class="mim-tip-reference" title="Kunkel, G. R., Lisciandro, H. G., Winter, H. L. <strong>The human chd8 gene is transcribed from two distant upstream promoters.</strong> Biochem. Biophys. Res. Commun. 532: 190-194, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32854944/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32854944</a>] [<a href="https://doi.org/10.1016/j.bbrc.2020.08.051" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32854944">Kunkel et al. (2020)</a> showed that human CHD8 was transcribed from 2 far upstream promoters. RNA polymerase II (see <a href="/entry/180660">180660</a>) occupancy levels on each of the promoters were similar in HEK293 cells. RACE analysis showed that both promoters drove CHD8 transcription from a dispersed set of transcriptional start sites. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32854944" 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="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 7/1/2021."None>Gross (2021)</a> mapped the CHD8 gene to chromosome 14q11.2 based on an alignment of the CHD8 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AB046784" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AB046784</a>) with the genomic sequence (GRCh38).</p><p><a href="#14" class="mim-tip-reference" title="Nishiyama, M., Nakayama, K., Tsunematsu, R., Tsukiyama, T., Kikuchi, A., Nakayama, K. I. <strong>Early embryonic death in mice lacking the beta-catenin-binding protein Duplin.</strong> Molec. Cell. Biol. 24: 8386-8394, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15367660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15367660</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15367660[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.24.19.8386-8394.2004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15367660">Nishiyama et al. (2004)</a> mapped the mouse Duplin gene to chromosome 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15367660" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#19" class="mim-tip-reference" title="Sakamoto, I., Kishida, S., Fukui, A., Kishida, M., Yamamoto, H., Hino, S., Michiue, T., Takada, S., Asashima, M., Kikuchi, A. <strong>A novel beta-catenin-binding protein inhibits beta-catenin-dependent Tcf activation and axis formation.</strong> J. Biol. Chem. 275: 32871-32878, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10921920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10921920</a>] [<a href="https://doi.org/10.1074/jbc.M004089200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10921920">Sakamoto et al. (2000)</a> found that rat Duplin bound directly to the armadillo repeats of beta-catenin (see CTNNB1; <a href="/entry/116806">116806</a>) in the nuclei of mammalian cells, thereby inhibiting binding of TCF4 (TCF7L2; <a href="/entry/602228">602228</a>) to beta-catenin and beta-catenin-dependent activation of TCF4. Expression of Duplin in Xenopus embryos inhibited axis formation and beta catenin-dependent axis duplication, and it countered the ability of beta-catenin to rescue ventralizing phenotypes induced by ultraviolet irradiation. <a href="#19" class="mim-tip-reference" title="Sakamoto, I., Kishida, S., Fukui, A., Kishida, M., Yamamoto, H., Hino, S., Michiue, T., Takada, S., Asashima, M., Kikuchi, A. <strong>A novel beta-catenin-binding protein inhibits beta-catenin-dependent Tcf activation and axis formation.</strong> J. Biol. Chem. 275: 32871-32878, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10921920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10921920</a>] [<a href="https://doi.org/10.1074/jbc.M004089200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10921920">Sakamoto et al. (2000)</a> concluded that Duplin is a nuclear protein that negatively regulates Wnt (see <a href="/entry/164820">164820</a>) signaling by binding beta-catenin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10921920" 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 yeast 2-hybrid analysis of a mouse brain cDNA library, followed by studies in COS cells, <a href="#8" class="mim-tip-reference" title="Kobayashi, M., Kishida, S., Fukui, A., Michiue, T., Miyamoto, Y., Okamoto, T., Yoneda, Y., Asashima, M., Kikuchi, A. <strong>Nuclear localization of Duplin, a beta-catenin-binding protein, is essential for its inhibitory activity on the Wnt signaling pathway.</strong> J. Biol. Chem. 277: 5816-5822, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11744694/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11744694</a>] [<a href="https://doi.org/10.1074/jbc.M108433200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11744694">Kobayashi et al. (2002)</a> found that importin-alpha (see KPNA2; <a href="/entry/600685">600685</a>) bound a cluster of basic amino acids in rat Duplin. Interaction with importin-alpha caused Duplin to translocate to the nucleus, and nuclear localization of Duplin was essential for inhibition of Wnt-dependent activation of TCF4 in mammalian cells and ventralization in Xenopus embryos. Additional experiments in Xenopus embryos showed that Duplin also inhibited the Wnt signaling pathway downstream of beta-catenin target genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11744694" 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 yeast 2-hybrid analysis and pull-down assays, <a href="#5" class="mim-tip-reference" title="Ishihara, K., Oshimura, M., Nakao, M. <strong>CTCF-dependent chromatin insulator is linked to epigenetic remodeling.</strong> Molec. Cell 23: 733-742, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16949368/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16949368</a>] [<a href="https://doi.org/10.1016/j.molcel.2006.08.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16949368">Ishihara et al. (2006)</a> found that the C-terminal region of mouse Chd8 interacted with the zinc finger domain of Ctcf (<a href="/entry/604167">604167</a>). Chromatin immunoprecipitation analysis of a human hepatoma cell line revealed that CHD8 was present at CTCF target sites, such as the differentially methylated region of H19 (<a href="/entry/103280">103280</a>), the locus control region of beta-globin (<a href="/entry/141900">141900</a>), and the promoter regions of the BRCA1 (<a href="/entry/113705">113705</a>) and MYC (<a href="/entry/190080">190080</a>) genes. Immunoprecipitation analysis demonstrated an endogenous complex of CHD8 and CTCF in HeLa cells. Knockdown of CHD8 in HeLa cells by RNA interference abolished the CTCF-dependent insulator activity of the H19 differentially methylated region, leading to reactivation of imprinted IGF2 (<a href="/entry/147470">147470</a>) from the maternal chromosome. Lack of CHD8 affected CpG methylation and histone acetylation around the CTCF-binding sites, which are adjacent to heterochromatin, of the BRCA1 and MYC genes. <a href="#5" class="mim-tip-reference" title="Ishihara, K., Oshimura, M., Nakao, M. <strong>CTCF-dependent chromatin insulator is linked to epigenetic remodeling.</strong> Molec. Cell 23: 733-742, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16949368/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16949368</a>] [<a href="https://doi.org/10.1016/j.molcel.2006.08.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16949368">Ishihara et al. (2006)</a> concluded that CTCF-CHD8 has a role in insulation and epigenetic regulation at active insulator sites. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16949368" 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 purified recombinant human protein, <a href="#22" class="mim-tip-reference" title="Thompson, B. A., Tremblay, V., Lin, G., Bochar, D. A. <strong>CHD8 is an ATP-dependent chromatin remodeling factor that regulates beta-catenin target genes.</strong> Molec. Cell. Biol. 28: 3894-3904, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18378692/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18378692</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18378692[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.00322-08" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18378692">Thompson et al. (2008)</a> showed that CHD8 was a remodeling enzyme capable of altering nucleosomal structure in an ATP-dependent manner. Purification of CHD8 from HeLa cells revealed that CHD8 was part of a 900-kD complex that also included WDR5 (<a href="/entry/609012">609012</a>), which interacted directly with CHD8 in the complex. CHD8 interacted directly with beta-catenin and bound to the proximal promoter regions of beta-catenin target genes to regulate beta-catenin-mediated transcription. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18378692" 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 a yeast 2-hybrid library screen, <a href="#2" class="mim-tip-reference" title="Batsukh, T., Pieper, L., Koszucka, A. M., von Velsen, N., Hoyer-Fender, S., Elbracht, M., Bergman, J. E. H., Hoefsloot, L. H., Pauli, S. <strong>CHD8 interacts with CHD7, a protein which is mutated in CHARGE syndrome.</strong> Hum. Molec. Genet. 19: 2858-2866, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20453063/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20453063</a>] [<a href="https://doi.org/10.1093/hmg/ddq189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20453063">Batsukh et al. (2010)</a> identified CHD8 as an interacting partner of CHD7 (<a href="/entry/608892">608892</a>), mutations in which cause the autosomal dominant malformation syndrome CHARGE (<a href="/entry/214800">214800</a>). In a direct yeast 2-hybrid system, the CHD7-CHD8 interaction was disrupted by CHD7 missense mutations found in CHARGE patients, including gly2108 to arg (<a href="/entry/608892#0011">608892.0011</a>), whereas in coimmunoprecipitation studies disruption of the CHD7-CHD8 interaction by the mutations could not be observed. The authors hypothesized that CHD7 and CHD8 proteins interact directly and indirectly via additional linker proteins. Disruption of the direct CHD7-CHD8 interaction may change the conformation of a putative large CHD7-CHD8 complex and could be a disease mechanism in CHARGE syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20453063" 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 RNA-sequencing and chromatin immunoprecipitation-sequencing analyses in CHD8-knockdown human neural progenitor cells (NPCs), <a href="#21" class="mim-tip-reference" title="Sugathan, A., Biagioli, M., Golzio, C., Erdin, S., Blumenthal, I., Manavalan, P., Ragavendran, A., Brand, H., Lucente, D., Miles, J., Sheridan, S. D., Stortchevoi, A., Kellis, M., Haggarty, S. J., Katsanis, N., Gusella, J. F., Talkowski, M. E. <strong>CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors.</strong> Proc. Nat. Acad. Sci. 111: E4468-E4477, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25294932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25294932</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25294932[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1405266111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25294932">Sugathan et al. (2014)</a> found that CHD8 regulated many functionally distinct genes associated with autism spectrum disorder (ASD; <a href="/entry/209850">209850</a>) and neurodevelopmental pathways. CHD8 also appeared to play a role in cancer formation through regulation of a distinct set of genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25294932" 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="#17" class="mim-tip-reference" title="O'Roak, B. J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B. P., Levy, R., Ko, A., Lee, C., Smith, J. D., Turner, E. H., Stanaway, I. B., and 11 others. <strong>Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.</strong> Nature 485: 246-250, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22495309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22495309</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22495309[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/nature10989" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22495309">O'Roak et al. (2012)</a> performed whole-exome sequencing for parent-child trios from the Simons Simplex collection of autism spectrum disorder patients, including 189 new trios and 20 that were previously reported (<a href="#15" class="mim-tip-reference" title="O'Roak, B. J., Deriziotis, P., Lee, C., Vives, L., Schwartz, J. J., Girirajan, S., Karakoc, E., Mackenzie, A. P., Ng, S. B., Baker, C., Rieder, M. J., Nickerson, D. A., Bernier, R., Fisher, S. E., Shendure, J., Eichler, E. E. <strong>Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.</strong> Nature Genet. 43: 585-589, 2011. Note: Erratum: Nature Genet. 44: 471 only, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21572417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21572417</a>] [<a href="https://doi.org/10.1038/ng.835" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21572417">O'Roak et al., 2011</a>). Some of the patients had significantly impaired intellectual development In addition, <a href="#17" class="mim-tip-reference" title="O'Roak, B. J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B. P., Levy, R., Ko, A., Lee, C., Smith, J. D., Turner, E. H., Stanaway, I. B., and 11 others. <strong>Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.</strong> Nature 485: 246-250, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22495309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22495309</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22495309[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/nature10989" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22495309">O'Roak et al. (2012)</a> sequenced the exomes of 50 unaffected sibs corresponding to 31 of the new and 19 of the previously reported trios, for a total of 677 individual exomes from 209 families. In proband exomes, <a href="#17" class="mim-tip-reference" title="O'Roak, B. J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B. P., Levy, R., Ko, A., Lee, C., Smith, J. D., Turner, E. H., Stanaway, I. B., and 11 others. <strong>Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.</strong> Nature 485: 246-250, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22495309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22495309</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22495309[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/nature10989" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22495309">O'Roak et al. (2012)</a> reported 2 de novo disruptive mutations in CHD8, which they described as a nonsense mutation and a frameshift indel, in patients with intellectual developmental disorder with autism and macrocephaly (IDDAM; <a href="/entry/615032">615032</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22495309+21572417" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a study of exonic de novo mutations in autism spectrum disorders, <a href="#13" class="mim-tip-reference" title="Neale, B. M., Kou, Y., Liu, L., Ma'ayan, A., Samocha, K. E., Sabo, A., Lin, C.-F., Stevens, C., Wang, L.-S., Makarov, V., Polak, P., Yoon, S., and 47 others. <strong>Patterns and rates of exonic de novo mutations in autism spectrum disorders.</strong> Nature 485: 242-245, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22495311/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22495311</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22495311[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/nature11011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22495311">Neale et al. (2012)</a> stated that they had identified 3 loss-of-function mutations in the CHD8 gene among 935 cases and no mutations in CHD8 among 870 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22495311" 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>Among 2,446 probands from the Simons Simplex Collection including patients with impaired intellectual development, <a href="#16" class="mim-tip-reference" title="O'Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., Munson, J., Hiatt, J. B., and 14 others. <strong>Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.</strong> Science 338: 1619-1622, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23160955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23160955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23160955[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/10.1126/science.1227764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23160955">O'Roak et al. (2012)</a> identified 9 de novo mutations in the CHD8 gene, including 3 frameshift (e.g., <a href="#0002">610528.0002</a>), 4 nonsense (e.g., <a href="#0001">610528.0001</a>), an in-frame deletion (<a href="#0009">610528.0009</a>), and a splice site mutation (<a href="#0003">610528.0003</a>) in 9 children (2 females and 7 males). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23160955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 17-year-old boy with IDDAM, <a href="#11" class="mim-tip-reference" title="Merner, N., Forgeot d'Arc, B., Bell, S. C., Maussion, G., Peng, H., Gauthier, J., Crapper, L., Hamdan, F. F., Michaud, J. L., Mottron, L., Rouleau, G. A., Ernst, C. <strong>A de novo frameshift mutation in chromodomain helicase DNA-binding domain 8 (CHD8): a case report and literature review.</strong> Am. J. Med. Genet. 170A: 1225-1235, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26789910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26789910</a>] [<a href="https://doi.org/10.1002/ajmg.a.37566" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26789910">Merner et al. (2016)</a> identified a de novo heterozygous 1-bp duplication in the CHD8 gene (<a href="#0010">610528.0010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26789910" 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 10 newly identified, unrelated patients with IDDAM, <a href="#3" class="mim-tip-reference" title="Douzgou, S., Liang, H. W., Metcalfe, K., Somarathi, S., Tischkowitz, M., Mohamed, W., Kini, U., McKee, S., Yates, L., Bertoli, M., Lynch, S. A., Holder, S., the Deciphering Developmental Disorders Study, Banka, S. <strong>The clinical presentation caused by truncating CHD8 variants.</strong> Clin. Genet. 96: 72-84, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31001818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31001818</a>] [<a href="https://doi.org/10.1111/cge.13554" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31001818">Douzgou et al. (2019)</a> identified 10 different heterozygous mutations in the CHD8 gene, including 2 splicing, 6 nonsense, and 2 frameshift. Eight of the mutations were confirmed to be de novo; in the other 2 cases, parental inheritance was unknown. None of the mutations were present in the gnomAD database. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31001818" 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 27 patients with IDDAM, 10 of whom had previously been reported, <a href="#18" class="mim-tip-reference" title="Ostrowski, P. J., Zachariou, A., Loveday, C., Beleza-Meireles, A., Bertoli, M., Dean, J., Douglas, A. G. L., Ellis, I., Foster, A., Graham, J. M., Hague, J., Hilhorst-Hofstee, Y., and 23 others. <strong>The CHD8 overgrowth syndrome: a detailed evaluation of an emerging overgrowth phenotype in 27 patients.</strong> Am. J. Med. Genet. 181C: 557-564, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31721432/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31721432</a>] [<a href="https://doi.org/10.1002/ajmg.c.31749" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31721432">Ostrowski et al. (2019)</a> identified heterozygous mutations in the CHD8 gene, including 2 missense and 24 null mutations. The null mutations were distributed throughout the gene. One mutation (R564X) was identified in 2 unrelated patients. Twenty-four mutations were determined to be de novo and 3 were maternally inherited. One of these mothers had mild intellectual disability. In this patient cohort, there was a male to female ratio of 21:6. <a href="#18" class="mim-tip-reference" title="Ostrowski, P. J., Zachariou, A., Loveday, C., Beleza-Meireles, A., Bertoli, M., Dean, J., Douglas, A. G. L., Ellis, I., Foster, A., Graham, J. M., Hague, J., Hilhorst-Hofstee, Y., and 23 others. <strong>The CHD8 overgrowth syndrome: a detailed evaluation of an emerging overgrowth phenotype in 27 patients.</strong> Am. J. Med. Genet. 181C: 557-564, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31721432/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31721432</a>] [<a href="https://doi.org/10.1002/ajmg.c.31749" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31721432">Ostrowski et al. (2019)</a> suggested that females might present with a milder, subclinical phenotype due to gender-specific effects on transcriptional regulation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31721432" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="An, Y., Zhang, L., Liu, W., Jiang, Y., Chen, X., Lan, X., Li, G., Hang, Q., Wang, J., Gusella, J. F., Du, Y., Shen, Y. <strong>De novo variants in the helicase-C domain of CHD8 are associated with severe phenotypes including autism, language disability and overgrowth.</strong> Hum. Genet. 139: 499-512, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31980904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31980904</a>] [<a href="https://doi.org/10.1007/s00439-020-02115-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31980904">An et al. (2020)</a> screened a cohort of 96 patients with autism spectrum disorder by next-generation sequencing of a gene panel including the CHD8 gene. Three patients were identified with de novo heterozygous mutations in CHD8 (R1188X, <a href="#0011">610528.0011</a>; c.4818-1G-A, <a href="#0013">610528.0013</a>; Y1168N, <a href="#0014">610528.0014</a>). <a href="#1" class="mim-tip-reference" title="An, Y., Zhang, L., Liu, W., Jiang, Y., Chen, X., Lan, X., Li, G., Hang, Q., Wang, J., Gusella, J. F., Du, Y., Shen, Y. <strong>De novo variants in the helicase-C domain of CHD8 are associated with severe phenotypes including autism, language disability and overgrowth.</strong> Hum. Genet. 139: 499-512, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31980904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31980904</a>] [<a href="https://doi.org/10.1007/s00439-020-02115-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31980904">An et al. (2020)</a> identified an additional patient with autism spectrum disorder and a de novo heterozygous mutation (E689X; <a href="#0012">610528.0012</a>) in the CHD8 gene by trio whole-exome sequencing. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31980904" 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="#10" class="mim-tip-reference" title="Lee, C. Y., Petkova, M., Morales-Gonzalez, S., Gimber, N., Schmoranzer, J., Meisel, A., Bohmerle, W., Stenzel, W., Schuelke, M., Schwarz, J. M. <strong>A spontaneous missense mutation in the chromodomain helicase DNA-binding protein 8 (CHD8) gene: a novel association with congenital myasthenic syndrome.</strong> Neuropath. Appl. Neurobiol. 46: 588-601, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32267004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32267004</a>] [<a href="https://doi.org/10.1111/nan.12617" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32267004">Lee et al. (2020)</a> reported 14-year-old female monozygotic twins with a congenital myasthenic syndrome (see, e.g., <a href="/entry/601462">601462</a>) with a de novo c.1732C-T transition (NM_001170629) in the CHD8 gene, resulting in an R578C substitution at a highly conserved residue in the glutamine-rich domain. The mutation was identified by whole-exome sequencing and confirmed by Sanger sequencing. The mutation was predicted to affect protein folding and interactions with CHD8 binding partners. The sibs' clinical features included myasthenia, muscle weakness, ptosis, macrocephaly, and overgrowth. They were assessed as having average school performance with slightly below average long-term retrieval and fluid reasoning skills. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32267004" 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="#14" class="mim-tip-reference" title="Nishiyama, M., Nakayama, K., Tsunematsu, R., Tsukiyama, T., Kikuchi, A., Nakayama, K. I. <strong>Early embryonic death in mice lacking the beta-catenin-binding protein Duplin.</strong> Molec. Cell. Biol. 24: 8386-8394, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15367660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15367660</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15367660[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.24.19.8386-8394.2004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15367660">Nishiyama et al. (2004)</a> found that development of Duplin -/- mouse embryos was arrested at gastrulation, with the embryos manifesting massive apoptosis. In contrast, Duplin +/- mice appeared normal and were fertile. Expression of beta-catenin target genes was not increased in Duplin -/- embryos, suggesting that the lack of Duplin did not result in constitutive activation of Wnt signaling during embryogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15367660" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Sugathan, A., Biagioli, M., Golzio, C., Erdin, S., Blumenthal, I., Manavalan, P., Ragavendran, A., Brand, H., Lucente, D., Miles, J., Sheridan, S. D., Stortchevoi, A., Kellis, M., Haggarty, S. J., Katsanis, N., Gusella, J. F., Talkowski, M. E. <strong>CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors.</strong> Proc. Nat. Acad. Sci. 111: E4468-E4477, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25294932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25294932</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25294932[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1405266111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25294932">Sugathan et al. (2014)</a> found that knockdown of chd8 expression in zebrafish resulted in macrocephaly, likely caused by disturbed neuronal proliferation at early developmental stages. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25294932" 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="#6" class="mim-tip-reference" title="Katayama, Y., Nishiyama, M., Shoji, H., Ohkawa, Y., Kawamura, A., Sato, T., Suyama, M., Takumi, T., Miyakawa, T., Nakayama, K. I. <strong>CHD8 haploinsufficiency results in autistic-like phenotypes in mice.</strong> Nature 537: 675-679, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27602517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27602517</a>] [<a href="https://doi.org/10.1038/nature19357" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27602517">Katayama et al. (2016)</a> demonstrated that mice heterozygous for Chd8 mutations manifest ASD-like behavioral characteristics including increased anxiety, repetitive behavior, and altered social behavior. CHD8 haploinsufficiency did not result in prominent changes in the expression of a few specific genes but instead gave rise to small but global changes in gene expression in the mouse brain, reminiscent of those in the brains of patients with ASD. Gene set enrichment analysis revealed that neurodevelopment was delayed in the mutant mouse embryos. Furthermore, reduced expression of CHD8 was associated with abnormal activation of RE-1 silencing transcription factor (REST; <a href="/entry/600571">600571</a>), which suppresses the transcription of many neuronal genes. REST activation was also observed in the brains of humans with ASD, and CHD8 was found to interact physically with REST in the mouse brain. <a href="#6" class="mim-tip-reference" title="Katayama, Y., Nishiyama, M., Shoji, H., Ohkawa, Y., Kawamura, A., Sato, T., Suyama, M., Takumi, T., Miyakawa, T., Nakayama, K. I. <strong>CHD8 haploinsufficiency results in autistic-like phenotypes in mice.</strong> Nature 537: 675-679, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27602517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27602517</a>] [<a href="https://doi.org/10.1038/nature19357" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27602517">Katayama et al. (2016)</a> concluded that their results were consistent with the notion that CHD8 haploinsufficiency is a highly penetrant risk factor for ASD, with disease pathogenesis probably resulting from a delay in neurodevelopment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27602517" 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="Kawamura, A., Katayama, Y., Kakegawa, W., Ino, D., Nishiyama, M., Yuzaki, M., Nakayama, K. I. <strong>The autism-associated protein CHD8 is required for cerebellar development and motor function.</strong> Cell Rep. 35: 108932, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33826902/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33826902</a>] [<a href="https://doi.org/10.1016/j.celrep.2021.108932" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33826902">Kawamura et al. (2021)</a> found that mice with Chd8 deletion in brain were born approximately at the expected mendelian ratio, but that they subsequently showed growth retardation and cerebellar hypoplasia, and most died before 3 weeks of age. Analysis of mice with cerebellar granule neuron progenitor (GNP)-specific deletion of Chd8 showed that cerebellar hypoplasia resulted from a GNP-autonomous defect induced by Chd8 loss. Chd8 regulated proliferation and differentiation of GNPs, and cerebellar hypoplasia associated with Chd8 ablation resulted from attenuated proliferation and premature differentiation of Chd8-deficient GNPs. Chd8 was also required for pre- and postsynaptic integrity of CGNs, as electrophysiologic analysis revealed reduction in both pre- and postsynaptic function in mice with GNP-specific deletion of Chd8. Behavioral tests showed that GNP-specific Chd8-deficient mice manifested a motor behavioral defect, but not ASD-related behaviors. Chd8 was essential for activation of neuronal gene expression during GNP differentiation, and Chd8 deficiency attenuated proliferative capacity of progenitor cells by inhibiting expression of cell-cycle regulators at the transcriptional level. By conferring an accessible chromatin landscape and transactivating genes, CHD8 promoted GNP differentiation and contributed to GNP development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33826902" 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=610528[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<p>In a 55-month-old non-Hispanic white male with intellectual developmental disorder with autism and macrocephaly (IDDAM; <a href="/entry/615032">615032</a>), <a href="#16" class="mim-tip-reference" title="O'Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., Munson, J., Hiatt, J. B., and 14 others. <strong>Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.</strong> Science 338: 1619-1622, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23160955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23160955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23160955[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/10.1126/science.1227764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23160955">O'Roak et al. (2012)</a> identified a de novo heterozygous nonsense mutation in the CHD8 gene, a ser-to-ter substitution at codon 62 (S62X). The boy had a low verbal IQ of 75, nonverbal IQ of 78, and below average adaptive score of 80. His head circumference was 53 cm (z score = 1.0). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23160955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a 67-month-old non-Hispanic white male with intellectual developmental disorder with autism and macrocephaly (IDDAM; <a href="/entry/615032">615032</a>), <a href="#16" class="mim-tip-reference" title="O'Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., Munson, J., Hiatt, J. B., and 14 others. <strong>Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.</strong> Science 338: 1619-1622, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23160955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23160955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23160955[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/10.1126/science.1227764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23160955">O'Roak et al. (2012)</a> detected a heterozygous de novo 1-basepair insertion in the CHD8 gene that resulted in premature termination of the protein (tyr747 to ter; Y747X). The proband was nonverbal with extremely low verbal IQ of 25, nonverbal IQ of 38, and adaptive score of 57. His head circumference was 55 cm (z score = 2.0). He was diagnosed with cerebral palsy and was excessively clumsy and uncoordinated at 18 months. MRI/CT at 18 months was normal; EEG was normal at 24 months. The proband had a healthy 4-year-old sister. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23160955" 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>.0003 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000032828 OR RCV001291274 OR RCV001555708" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032828, RCV001291274, RCV001555708" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032828...</a>
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<p>In a 96-month-old non-Hispanic white female with intellectual developmental disorder with autism and macrocephaly (IDDAM; <a href="/entry/615032">615032</a>), <a href="#16" class="mim-tip-reference" title="O'Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., Munson, J., Hiatt, J. B., and 14 others. <strong>Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.</strong> Science 338: 1619-1622, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23160955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23160955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23160955[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/10.1126/science.1227764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23160955">O'Roak et al. (2012)</a> detected a de novo heterozygous splice site mutation (3519-2A-G) in the helicase superfamily C-terminal (HELC) domain of the CHD8 gene. She had a verbal IQ of 47 and a nonverbal IQ of 41, with clinical range deficits in social responsiveness and adaptive skills. She had experienced a delay in phrased speech. Her head circumference was 55.2 (z score = 2.3). She had a history of antiepileptic and antibiotic medication use, but not of seizures. MRI and EEG at age 5 were normal. A 6-year-old sister was healthy with normal head circumference. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23160955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397514551 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514551;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=rs397514551" 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=rs397514551" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In an 8-year-old non-Hispanic white male with intellectual developmental disorder with autism and macrocephaly (IDDAM; <a href="/entry/615032">615032</a>), <a href="#16" class="mim-tip-reference" title="O'Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., Munson, J., Hiatt, J. B., and 14 others. <strong>Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.</strong> Science 338: 1619-1622, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23160955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23160955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23160955[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/10.1126/science.1227764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23160955">O'Roak et al. (2012)</a> detected a heterozygous de novo nonsense mutation in the CHD8 gene, gln1238 to ter (Q1238X). In addition to the CHD8 mutation, the patient also carried a CUBN (<a href="/entry/602997">602997</a>) de novo nonsense mutation and 2 inherited copy number variations. The patient had an extremely low verbal IQ of 20, nonverbal IQ of 34, and low adaptive score of 59. He had macrocephaly (z score = 2.62) and normal BMI. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23160955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397514552 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514552;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=rs397514552" 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=rs397514552" 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=RCV000032830 OR RCV004700297" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032830, RCV004700297" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032830...</a>
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<p>In a 63-month-old non-Hispanic white male with intellectual developmental disorder with autism and macrocephaly (IDDAM; <a href="/entry/615032">615032</a>), <a href="#16" class="mim-tip-reference" title="O'Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., Munson, J., Hiatt, J. B., and 14 others. <strong>Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.</strong> Science 338: 1619-1622, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23160955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23160955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23160955[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/10.1126/science.1227764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23160955">O'Roak et al. (2012)</a> detected a heterozygous de novo substitution at codon 1337 of the CHD8 gene (arg1337 to ter, R1337X). The patient was 1 of 4 children born to the same parents and the third of 6 pregnancies (the mother's first and fourth pregnancies resulted in miscarriage within 13 weeks). Verbal IQ was low (79), nonverbal IQ average (92), and adaptive score low (58). His head circumference was 55.4 cm (z score = 2.5). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23160955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1887639311 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1887639311;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=rs1887639311" 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=rs1887639311" 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=RCV000032831 OR RCV005089332" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032831, RCV005089332" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032831...</a>
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<p>In a 12-year-old non-Hispanic white male with intellectual developmental disorder with autism and macrocephaly (IDDAM; <a href="/entry/615032">615032</a>), <a href="#16" class="mim-tip-reference" title="O'Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., Munson, J., Hiatt, J. B., and 14 others. <strong>Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.</strong> Science 338: 1619-1622, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23160955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23160955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23160955[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/10.1126/science.1227764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23160955">O'Roak et al. (2012)</a> identified a de novo heterozygous frameshift mutation in the CHD8 gene (Glu2103ArgfsTer3). The patient had a verbal IQ of 60, nonverbal IQ of 67, and adaptive score of 73. He was diagnosed as excessively clumsy and uncoordinated at age 3. The patient showed clinical range deficits in social responsiveness and elevation in anxious/depressed mood, and had a mixed expressive-receptive language disorder and pragmatic language disorder. He had chronic diarrhea from age 5 to 8 years. He had an abnormal EEG and seizures at age 12 years concurrent with a head injury. His head circumference was 58 cm (z score = 2.7). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23160955" 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>.0007 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1887627866 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1887627866;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=rs1887627866" 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=rs1887627866" 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=RCV000032832" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032832" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032832</a>
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<p>In a 55-month-old non-Hispanic white female with intellectual developmental disorder with autism and macrocephaly (IDDAM; <a href="/entry/615032">615032</a>), <a href="#16" class="mim-tip-reference" title="O'Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., Munson, J., Hiatt, J. B., and 14 others. <strong>Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.</strong> Science 338: 1619-1622, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23160955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23160955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23160955[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/10.1126/science.1227764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23160955">O'Roak et al. (2012)</a> identified a heterozygous de novo frameshift mutation in the CHD8 gene, a 2-basepair deletion resulting in premature termination of the protein (Leu2120ProfsTer13). The patient also carried a de novo nonsense mutations in the ETFB gene (<a href="/entry/130410">130410</a>) and the IQGAP2 gene (<a href="/entry/605401">605401</a>). She had normative range verbal IQ of 90 and nonverbal IQ of 93, but low adaptive behavioral skills score of 59. She had a large head (z score = 2.40). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23160955" 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>.0008 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs751094013 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs751094013;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs751094013?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs751094013" 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=rs751094013" 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=RCV001374912 OR RCV002251588 OR RCV004550095 OR RCV005051899" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001374912, RCV002251588, RCV004550095, RCV005051899" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001374912...</a>
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<p>In a 16-year-old non-Hispanic white male with intellectual developmental disorder with autism and macrocephaly (IDDAM; <a href="/entry/615032">615032</a>), <a href="#16" class="mim-tip-reference" title="O'Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., Munson, J., Hiatt, J. B., and 14 others. <strong>Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.</strong> Science 338: 1619-1622, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23160955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23160955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23160955[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/10.1126/science.1227764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23160955">O'Roak et al. (2012)</a> identified a heterozygous de novo 1-basepair insertion of a T nucleotide in the CHD8 gene, resulting in frameshift and premature termination of the protein (Asn2371LysfsTer2). The patient had an extremely low verbal IQ of 6, nonverbal IQ of 19, and adaptive score of 39. His head circumference was 60.8 cm (z score = 3.0). Loss of language skills during early development and attention problems were reported. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23160955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs774490485 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs774490485;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs774490485?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs774490485" 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=rs774490485" 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=RCV000032834 OR RCV003556095" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032834, RCV003556095" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032834...</a>
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<p>In a 13-year-old non-Hispanic white male with intellectual developmental disorder with autism and macrocephaly (IDDAM; <a href="/entry/615032">615032</a>), <a href="#16" class="mim-tip-reference" title="O'Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., Munson, J., Hiatt, J. B., and 14 others. <strong>Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.</strong> Science 338: 1619-1622, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23160955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23160955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23160955[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/10.1126/science.1227764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23160955">O'Roak et al. (2012)</a> identified a heterozygous de novo in-frame deletion of 3 nucleotides in the CHD8 gene resulting in deletion of histidine-2498 (His2498del). The patient had a verbal IQ of 84, nonverbal IQ of 98, and very low adaptive score of 66. His head circumference was 57 cm (z score = 1.6). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23160955" 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>.0010 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001374912 OR RCV002251588 OR RCV004550095 OR RCV005051899" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001374912, RCV002251588, RCV004550095, RCV005051899" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001374912...</a>
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<p>In a 17-year-old boy with intellectual developmental disorder with autism and macrocephaly (IDDAM; <a href="/entry/615032">615032</a>), <a href="#11" class="mim-tip-reference" title="Merner, N., Forgeot d'Arc, B., Bell, S. C., Maussion, G., Peng, H., Gauthier, J., Crapper, L., Hamdan, F. F., Michaud, J. L., Mottron, L., Rouleau, G. A., Ernst, C. <strong>A de novo frameshift mutation in chromodomain helicase DNA-binding domain 8 (CHD8): a case report and literature review.</strong> Am. J. Med. Genet. 170A: 1225-1235, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26789910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26789910</a>] [<a href="https://doi.org/10.1002/ajmg.a.37566" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26789910">Merner et al. (2016)</a> identified a heterozygous 1-bp duplication (c.6276dupA, NM_020920.3) in the CHD8 gene, predicted to result in a frameshift and premature termination (Asn2092LysfsTer2). The mutation, which was identified by sequencing of the CHD8 gene, occurred de novo. The mutation was not present in the dbSNP and ExAC databases. CHD8 mRNA and protein expression was reduced in patient lymphoblastoid cell lines compared to controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26789910" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0011 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1555314911 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1555314911;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=rs1555314911" 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=rs1555314911" 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=RCV001171595 OR RCV002249752" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001171595, RCV002249752" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001171595...</a>
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<p>In a 16-year-old boy with intellectual developmental disorder with autism and macrocephaly (IDDAM; <a href="/entry/615032">615032</a>), <a href="#1" class="mim-tip-reference" title="An, Y., Zhang, L., Liu, W., Jiang, Y., Chen, X., Lan, X., Li, G., Hang, Q., Wang, J., Gusella, J. F., Du, Y., Shen, Y. <strong>De novo variants in the helicase-C domain of CHD8 are associated with severe phenotypes including autism, language disability and overgrowth.</strong> Hum. Genet. 139: 499-512, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31980904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31980904</a>] [<a href="https://doi.org/10.1007/s00439-020-02115-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31980904">An et al. (2020)</a> identified a de novo heterozygous c.3562C-T transition (c.3562C-T, NM_001170629.1) in exon 17 of the CHD8 gene, resulting in an arg1188-to-ter (R1188X) substitution. The mutation, which was found by next-generation sequencing of a panel of genes and confirmed by Sanger sequencing, was not identified in either parent. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31980904" 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>.0012 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1555316331 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1555316331;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=rs1555316331" 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=rs1555316331" 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=RCV002248472" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002248472" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002248472</a>
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<p>In a 6-year-old boy with intellectual developmental disorder with autism and macrocephaly (IDDAM; <a href="/entry/615032">615032</a>), <a href="#1" class="mim-tip-reference" title="An, Y., Zhang, L., Liu, W., Jiang, Y., Chen, X., Lan, X., Li, G., Hang, Q., Wang, J., Gusella, J. F., Du, Y., Shen, Y. <strong>De novo variants in the helicase-C domain of CHD8 are associated with severe phenotypes including autism, language disability and overgrowth.</strong> Hum. Genet. 139: 499-512, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31980904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31980904</a>] [<a href="https://doi.org/10.1007/s00439-020-02115-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31980904">An et al. (2020)</a> identified a de novo heterozygous c.2065C-A transversion (c.2065C-A, NM_001170629.1) in exon 8 of the CHD8 gene, resulting in a glu689-to-ter (E689X) substitution. The mutation, which was identified by trio whole-exome sequencing and confirmed by Sanger sequencing, was not identified in the parents. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31980904" 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 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2139460816 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2139460816;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=rs2139460816" 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=rs2139460816" 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=RCV002248473" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002248473" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002248473</a>
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<p>In an 11-year-old boy with intellectual developmental disorder with autism and macrocephaly (IDDAM; <a href="/entry/615032">615032</a>), <a href="#1" class="mim-tip-reference" title="An, Y., Zhang, L., Liu, W., Jiang, Y., Chen, X., Lan, X., Li, G., Hang, Q., Wang, J., Gusella, J. F., Du, Y., Shen, Y. <strong>De novo variants in the helicase-C domain of CHD8 are associated with severe phenotypes including autism, language disability and overgrowth.</strong> Hum. Genet. 139: 499-512, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31980904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31980904</a>] [<a href="https://doi.org/10.1007/s00439-020-02115-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31980904">An et al. (2020)</a> identified a de novo heterozygous c.4818-1G-A transition (c.4818-1G-A, NM_0011700629.1) in intron 24 the CHD8 gene, predicted to result in a splicing abnormality and skipping of exon 25. The mutation, which was found by next-generation sequencing of a panel of genes and confirmed by Sanger sequencing, was not identified in either parent. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31980904" 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>.0014 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2139469836 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2139469836;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=rs2139469836" 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=rs2139469836" 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=RCV002248474" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002248474" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002248474</a>
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<p>In a 12-year-old boy with intellectual developmental disorder with autism and macrocephaly (IDDAM; <a href="/entry/615032">615032</a>), <a href="#1" class="mim-tip-reference" title="An, Y., Zhang, L., Liu, W., Jiang, Y., Chen, X., Lan, X., Li, G., Hang, Q., Wang, J., Gusella, J. F., Du, Y., Shen, Y. <strong>De novo variants in the helicase-C domain of CHD8 are associated with severe phenotypes including autism, language disability and overgrowth.</strong> Hum. Genet. 139: 499-512, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31980904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31980904</a>] [<a href="https://doi.org/10.1007/s00439-020-02115-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31980904">An et al. (2020)</a> identified a de novo heterozygous c.3502T-A transversion (c.3502T-A, NM_001170629.1) in exon 16 of the CHD8 gene, resulting in a tyr1168-to-asn (Y1168N) substitution. The mutation, which was identified by next-generation sequencing of a panel of genes and confirmed by Sanger sequencing, was not identified in either parent. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31980904" 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="#Sanders2012" class="mim-tip-reference" title="Sanders, S. J., Murtha, M. T., Gupta, A. R., Murdoch, J. D., Raubeson, M. J., Willsey, A. J., Ercan-Sencicek, A. G., DiLullo, N. M., Parikshak, N. N., Stein, J. L., Walker, M. F., Ober, G. T., and 18 others. <strong>De novo mutations revealed by whole-exome sequencing are strongly associated with autism.</strong> Nature 485: 237-241, 2012.">Sanders et al. (2012)</a>
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An, Y., Zhang, L., Liu, W., Jiang, Y., Chen, X., Lan, X., Li, G., Hang, Q., Wang, J., Gusella, J. F., Du, Y., Shen, Y.
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<strong>De novo variants in the helicase-C domain of CHD8 are associated with severe phenotypes including autism, language disability and overgrowth.</strong>
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Hum. Genet. 139: 499-512, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31980904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31980904</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31980904" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s00439-020-02115-9" target="_blank">Full Text</a>]
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Batsukh, T., Pieper, L., Koszucka, A. M., von Velsen, N., Hoyer-Fender, S., Elbracht, M., Bergman, J. E. H., Hoefsloot, L. H., Pauli, S.
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<strong>CHD8 interacts with CHD7, a protein which is mutated in CHARGE syndrome.</strong>
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Hum. Molec. Genet. 19: 2858-2866, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20453063/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20453063</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20453063" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddq189" target="_blank">Full Text</a>]
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<a id="Douzgou2019" class="mim-anchor"></a>
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Douzgou, S., Liang, H. W., Metcalfe, K., Somarathi, S., Tischkowitz, M., Mohamed, W., Kini, U., McKee, S., Yates, L., Bertoli, M., Lynch, S. A., Holder, S., the Deciphering Developmental Disorders Study, Banka, S.
|
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<strong>The clinical presentation caused by truncating CHD8 variants.</strong>
|
|
Clin. Genet. 96: 72-84, 2019.
|
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|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31001818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31001818</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31001818" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Gross, M. B.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 7/1/2021.
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|
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|
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Ishihara, K., Oshimura, M., Nakao, M.
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<strong>CTCF-dependent chromatin insulator is linked to epigenetic remodeling.</strong>
|
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Molec. Cell 23: 733-742, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16949368/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16949368</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16949368" 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.molcel.2006.08.008" target="_blank">Full Text</a>]
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Katayama, Y., Nishiyama, M., Shoji, H., Ohkawa, Y., Kawamura, A., Sato, T., Suyama, M., Takumi, T., Miyakawa, T., Nakayama, K. I.
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<strong>CHD8 haploinsufficiency results in autistic-like phenotypes in mice.</strong>
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Nature 537: 675-679, 2016.
|
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27602517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27602517</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27602517" 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/nature19357" target="_blank">Full Text</a>]
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|
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Kawamura, A., Katayama, Y., Kakegawa, W., Ino, D., Nishiyama, M., Yuzaki, M., Nakayama, K. I.
|
|
<strong>The autism-associated protein CHD8 is required for cerebellar development and motor function.</strong>
|
|
Cell Rep. 35: 108932, 2021.
|
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|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33826902/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33826902</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33826902" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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Kobayashi, M., Kishida, S., Fukui, A., Michiue, T., Miyamoto, Y., Okamoto, T., Yoneda, Y., Asashima, M., Kikuchi, A.
|
|
<strong>Nuclear localization of Duplin, a beta-catenin-binding protein, is essential for its inhibitory activity on the Wnt signaling pathway.</strong>
|
|
J. Biol. Chem. 277: 5816-5822, 2002.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11744694/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11744694</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11744694" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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Kunkel, G. R., Lisciandro, H. G., Winter, H. L.
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<strong>The human chd8 gene is transcribed from two distant upstream promoters.</strong>
|
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Biochem. Biophys. Res. Commun. 532: 190-194, 2020.
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32854944/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32854944</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32854944" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Lee, C. Y., Petkova, M., Morales-Gonzalez, S., Gimber, N., Schmoranzer, J., Meisel, A., Bohmerle, W., Stenzel, W., Schuelke, M., Schwarz, J. M.
|
|
<strong>A spontaneous missense mutation in the chromodomain helicase DNA-binding protein 8 (CHD8) gene: a novel association with congenital myasthenic syndrome.</strong>
|
|
Neuropath. Appl. Neurobiol. 46: 588-601, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32267004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32267004</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32267004" 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/nan.12617" target="_blank">Full Text</a>]
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Merner, N., Forgeot d'Arc, B., Bell, S. C., Maussion, G., Peng, H., Gauthier, J., Crapper, L., Hamdan, F. F., Michaud, J. L., Mottron, L., Rouleau, G. A., Ernst, C.
|
|
<strong>A de novo frameshift mutation in chromodomain helicase DNA-binding domain 8 (CHD8): a case report and literature review.</strong>
|
|
Am. J. Med. Genet. 170A: 1225-1235, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26789910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26789910</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26789910" 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.37566" target="_blank">Full Text</a>]
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Nagase, T., Kikuno, R., Nakayama, M., Hirosawa, M., Ohara, O.
|
|
<strong>Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</strong>
|
|
DNA Res. 7: 273-281, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10997877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10997877</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10997877" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/dnares/7.4.271" target="_blank">Full Text</a>]
|
|
|
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|
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|
|
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|
|
|
|
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|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Neale2012" class="mim-anchor"></a>
|
|
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|
|
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|
|
Neale, B. M., Kou, Y., Liu, L., Ma'ayan, A., Samocha, K. E., Sabo, A., Lin, C.-F., Stevens, C., Wang, L.-S., Makarov, V., Polak, P., Yoon, S., and 47 others.
|
|
<strong>Patterns and rates of exonic de novo mutations in autism spectrum disorders.</strong>
|
|
Nature 485: 242-245, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22495311/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22495311</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22495311[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=22495311" 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/nature11011" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
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|
|
|
|
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|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Nishiyama2004" class="mim-anchor"></a>
|
|
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|
|
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|
|
Nishiyama, M., Nakayama, K., Tsunematsu, R., Tsukiyama, T., Kikuchi, A., Nakayama, K. I.
|
|
<strong>Early embryonic death in mice lacking the beta-catenin-binding protein Duplin.</strong>
|
|
Molec. Cell. Biol. 24: 8386-8394, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15367660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15367660</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15367660[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=15367660" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
|
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|
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[<a href="https://doi.org/10.1128/MCB.24.19.8386-8394.2004" target="_blank">Full Text</a>]
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|
|
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|
|
|
|
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|
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|
|
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|
|
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|
|
O'Roak, B. J., Deriziotis, P., Lee, C., Vives, L., Schwartz, J. J., Girirajan, S., Karakoc, E., Mackenzie, A. P., Ng, S. B., Baker, C., Rieder, M. J., Nickerson, D. A., Bernier, R., Fisher, S. E., Shendure, J., Eichler, E. E.
|
|
<strong>Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.</strong>
|
|
Nature Genet. 43: 585-589, 2011. Note: Erratum: Nature Genet. 44: 471 only, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21572417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21572417</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21572417" 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.835" target="_blank">Full Text</a>]
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|
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|
|
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|
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|
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|
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O'Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., Munson, J., Hiatt, J. B., and 14 others.
|
|
<strong>Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.</strong>
|
|
Science 338: 1619-1622, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23160955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23160955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23160955[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=23160955" 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.1227764" target="_blank">Full Text</a>]
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O'Roak, B. J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B. P., Levy, R., Ko, A., Lee, C., Smith, J. D., Turner, E. H., Stanaway, I. B., and 11 others.
|
|
<strong>Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.</strong>
|
|
Nature 485: 246-250, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22495309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22495309</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22495309[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=22495309" 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/nature10989" target="_blank">Full Text</a>]
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<a id="Ostrowski2019" class="mim-anchor"></a>
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Ostrowski, P. J., Zachariou, A., Loveday, C., Beleza-Meireles, A., Bertoli, M., Dean, J., Douglas, A. G. L., Ellis, I., Foster, A., Graham, J. M., Hague, J., Hilhorst-Hofstee, Y., and 23 others.
|
|
<strong>The CHD8 overgrowth syndrome: a detailed evaluation of an emerging overgrowth phenotype in 27 patients.</strong>
|
|
Am. J. Med. Genet. 181C: 557-564, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31721432/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31721432</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31721432" 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.c.31749" target="_blank">Full Text</a>]
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Sakamoto, I., Kishida, S., Fukui, A., Kishida, M., Yamamoto, H., Hino, S., Michiue, T., Takada, S., Asashima, M., Kikuchi, A.
|
|
<strong>A novel beta-catenin-binding protein inhibits beta-catenin-dependent Tcf activation and axis formation.</strong>
|
|
J. Biol. Chem. 275: 32871-32878, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10921920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10921920</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10921920" 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/10.1074/jbc.M004089200" target="_blank">Full Text</a>]
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Sanders, S. J., Murtha, M. T., Gupta, A. R., Murdoch, J. D., Raubeson, M. J., Willsey, A. J., Ercan-Sencicek, A. G., DiLullo, N. M., Parikshak, N. N., Stein, J. L., Walker, M. F., Ober, G. T., and 18 others.
|
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<strong>De novo mutations revealed by whole-exome sequencing are strongly associated with autism.</strong>
|
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Nature 485: 237-241, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22495306/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22495306</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22495306[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=22495306" 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/nature10945" target="_blank">Full Text</a>]
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Sugathan, A., Biagioli, M., Golzio, C., Erdin, S., Blumenthal, I., Manavalan, P., Ragavendran, A., Brand, H., Lucente, D., Miles, J., Sheridan, S. D., Stortchevoi, A., Kellis, M., Haggarty, S. J., Katsanis, N., Gusella, J. F., Talkowski, M. E.
|
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<strong>CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors.</strong>
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Proc. Nat. Acad. Sci. 111: E4468-E4477, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25294932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25294932</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25294932[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=25294932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.1405266111" target="_blank">Full Text</a>]
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Thompson, B. A., Tremblay, V., Lin, G., Bochar, D. A.
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<strong>CHD8 is an ATP-dependent chromatin remodeling factor that regulates beta-catenin target genes.</strong>
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Molec. Cell. Biol. 28: 3894-3904, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18378692/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18378692</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18378692[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=18378692" 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.00322-08" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 05/10/2022
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Matthew B. Gross - updated : 07/01/2021<br>Bao Lige - updated : 07/01/2021<br>Ada Hamosh - updated : 12/14/2016<br>George E. Tiller - updated : 9/5/2013<br>Ada Hamosh - updated : 1/23/2013<br>Ada Hamosh - updated : 6/29/2012
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Patricia A. Hartz : 11/6/2006
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carol : 05/10/2022<br>carol : 07/06/2021<br>mgross : 07/01/2021<br>mgross : 07/01/2021<br>carol : 05/12/2017<br>alopez : 12/14/2016<br>carol : 04/06/2016<br>tpirozzi : 10/1/2013<br>alopez : 9/17/2013<br>alopez : 9/5/2013<br>alopez : 1/24/2013<br>terry : 1/23/2013<br>alopez : 7/10/2012<br>terry : 7/6/2012<br>alopez : 7/5/2012<br>alopez : 7/5/2012<br>terry : 6/29/2012<br>mgross : 11/6/2006<br>mgross : 11/6/2006
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CHROMODOMAIN HELICASE DNA-BINDING PROTEIN 8; CHD8
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<span class="mim-font">
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AXIS DUPLICATION INHIBITOR; DUPLIN<br />
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KIAA1564
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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: CHD8</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: 14q11.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 14:21,385,199-21,456,123 </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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14q11.2
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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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Intellectual developmental disorder with autism and macrocephaly
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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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615032
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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">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>CHD8 is an ATP-dependent chromatin-remodeling factor that regulates transcription of beta-catenin (CTNNB1; 116806) target genes (Thompson et al., 2008). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By sequencing clones from a size-fractionated fetal brain cDNA library, Nagase et al. (2000) cloned CHD8, which they designated KIAA1564. The deduced protein contains 1,417 amino acids. RT-PCR ELISA detected moderate expression in all adult and fetal tissues and specific brain regions examined. </p><p>Sakamoto et al. (2000) cloned rat Chd8, which they called Duplin. The deduced 749-amino acid protein was expressed mainly in the nuclear fraction of transfected COS cells. </p><p>Ishihara et al. (2006) cloned mouse Chd8. The deduced 2,582-amino acid protein has 2 chromodomains, followed by a central helicase/ATPase domain and 2 C-terminal BRK domains. Northern blot analysis detected ubiquitous Chd8 expression in mouse tissues, with highest levels in heart and testis. Western blot analysis of HeLa cells detected endogenous CHD8 at an apparent molecular mass of 240 kD. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Nishiyama et al. (2004) determined that the mouse Chd8 gene contains 9 exons and spans about 13 kb. </p><p>By transient transfection assays in HEK293 cells, Kunkel et al. (2020) showed that human CHD8 was transcribed from 2 far upstream promoters. RNA polymerase II (see 180660) occupancy levels on each of the promoters were similar in HEK293 cells. RACE analysis showed that both promoters drove CHD8 transcription from a dispersed set of transcriptional start sites. </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>Gross (2021) mapped the CHD8 gene to chromosome 14q11.2 based on an alignment of the CHD8 sequence (GenBank AB046784) with the genomic sequence (GRCh38).</p><p>Nishiyama et al. (2004) mapped the mouse Duplin gene to chromosome 14. </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>Sakamoto et al. (2000) found that rat Duplin bound directly to the armadillo repeats of beta-catenin (see CTNNB1; 116806) in the nuclei of mammalian cells, thereby inhibiting binding of TCF4 (TCF7L2; 602228) to beta-catenin and beta-catenin-dependent activation of TCF4. Expression of Duplin in Xenopus embryos inhibited axis formation and beta catenin-dependent axis duplication, and it countered the ability of beta-catenin to rescue ventralizing phenotypes induced by ultraviolet irradiation. Sakamoto et al. (2000) concluded that Duplin is a nuclear protein that negatively regulates Wnt (see 164820) signaling by binding beta-catenin. </p><p>By yeast 2-hybrid analysis of a mouse brain cDNA library, followed by studies in COS cells, Kobayashi et al. (2002) found that importin-alpha (see KPNA2; 600685) bound a cluster of basic amino acids in rat Duplin. Interaction with importin-alpha caused Duplin to translocate to the nucleus, and nuclear localization of Duplin was essential for inhibition of Wnt-dependent activation of TCF4 in mammalian cells and ventralization in Xenopus embryos. Additional experiments in Xenopus embryos showed that Duplin also inhibited the Wnt signaling pathway downstream of beta-catenin target genes. </p><p>Using yeast 2-hybrid analysis and pull-down assays, Ishihara et al. (2006) found that the C-terminal region of mouse Chd8 interacted with the zinc finger domain of Ctcf (604167). Chromatin immunoprecipitation analysis of a human hepatoma cell line revealed that CHD8 was present at CTCF target sites, such as the differentially methylated region of H19 (103280), the locus control region of beta-globin (141900), and the promoter regions of the BRCA1 (113705) and MYC (190080) genes. Immunoprecipitation analysis demonstrated an endogenous complex of CHD8 and CTCF in HeLa cells. Knockdown of CHD8 in HeLa cells by RNA interference abolished the CTCF-dependent insulator activity of the H19 differentially methylated region, leading to reactivation of imprinted IGF2 (147470) from the maternal chromosome. Lack of CHD8 affected CpG methylation and histone acetylation around the CTCF-binding sites, which are adjacent to heterochromatin, of the BRCA1 and MYC genes. Ishihara et al. (2006) concluded that CTCF-CHD8 has a role in insulation and epigenetic regulation at active insulator sites. </p><p>Using purified recombinant human protein, Thompson et al. (2008) showed that CHD8 was a remodeling enzyme capable of altering nucleosomal structure in an ATP-dependent manner. Purification of CHD8 from HeLa cells revealed that CHD8 was part of a 900-kD complex that also included WDR5 (609012), which interacted directly with CHD8 in the complex. CHD8 interacted directly with beta-catenin and bound to the proximal promoter regions of beta-catenin target genes to regulate beta-catenin-mediated transcription. </p><p>Using a yeast 2-hybrid library screen, Batsukh et al. (2010) identified CHD8 as an interacting partner of CHD7 (608892), mutations in which cause the autosomal dominant malformation syndrome CHARGE (214800). In a direct yeast 2-hybrid system, the CHD7-CHD8 interaction was disrupted by CHD7 missense mutations found in CHARGE patients, including gly2108 to arg (608892.0011), whereas in coimmunoprecipitation studies disruption of the CHD7-CHD8 interaction by the mutations could not be observed. The authors hypothesized that CHD7 and CHD8 proteins interact directly and indirectly via additional linker proteins. Disruption of the direct CHD7-CHD8 interaction may change the conformation of a putative large CHD7-CHD8 complex and could be a disease mechanism in CHARGE syndrome. </p><p>Using RNA-sequencing and chromatin immunoprecipitation-sequencing analyses in CHD8-knockdown human neural progenitor cells (NPCs), Sugathan et al. (2014) found that CHD8 regulated many functionally distinct genes associated with autism spectrum disorder (ASD; 209850) and neurodevelopmental pathways. CHD8 also appeared to play a role in cancer formation through regulation of a distinct set of genes. </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>
|
|
<h4>
|
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<span class="mim-font">
|
|
<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">
|
|
<p>O'Roak et al. (2012) performed whole-exome sequencing for parent-child trios from the Simons Simplex collection of autism spectrum disorder patients, including 189 new trios and 20 that were previously reported (O'Roak et al., 2011). Some of the patients had significantly impaired intellectual development In addition, O'Roak et al. (2012) sequenced the exomes of 50 unaffected sibs corresponding to 31 of the new and 19 of the previously reported trios, for a total of 677 individual exomes from 209 families. In proband exomes, O'Roak et al. (2012) reported 2 de novo disruptive mutations in CHD8, which they described as a nonsense mutation and a frameshift indel, in patients with intellectual developmental disorder with autism and macrocephaly (IDDAM; 615032). </p><p>In a study of exonic de novo mutations in autism spectrum disorders, Neale et al. (2012) stated that they had identified 3 loss-of-function mutations in the CHD8 gene among 935 cases and no mutations in CHD8 among 870 controls. </p><p>Among 2,446 probands from the Simons Simplex Collection including patients with impaired intellectual development, O'Roak et al. (2012) identified 9 de novo mutations in the CHD8 gene, including 3 frameshift (e.g., 610528.0002), 4 nonsense (e.g., 610528.0001), an in-frame deletion (610528.0009), and a splice site mutation (610528.0003) in 9 children (2 females and 7 males). </p><p>In a 17-year-old boy with IDDAM, Merner et al. (2016) identified a de novo heterozygous 1-bp duplication in the CHD8 gene (610528.0010). </p><p>In 10 newly identified, unrelated patients with IDDAM, Douzgou et al. (2019) identified 10 different heterozygous mutations in the CHD8 gene, including 2 splicing, 6 nonsense, and 2 frameshift. Eight of the mutations were confirmed to be de novo; in the other 2 cases, parental inheritance was unknown. None of the mutations were present in the gnomAD database. Functional studies were not performed. </p><p>In 27 patients with IDDAM, 10 of whom had previously been reported, Ostrowski et al. (2019) identified heterozygous mutations in the CHD8 gene, including 2 missense and 24 null mutations. The null mutations were distributed throughout the gene. One mutation (R564X) was identified in 2 unrelated patients. Twenty-four mutations were determined to be de novo and 3 were maternally inherited. One of these mothers had mild intellectual disability. In this patient cohort, there was a male to female ratio of 21:6. Ostrowski et al. (2019) suggested that females might present with a milder, subclinical phenotype due to gender-specific effects on transcriptional regulation. </p><p>An et al. (2020) screened a cohort of 96 patients with autism spectrum disorder by next-generation sequencing of a gene panel including the CHD8 gene. Three patients were identified with de novo heterozygous mutations in CHD8 (R1188X, 610528.0011; c.4818-1G-A, 610528.0013; Y1168N, 610528.0014). An et al. (2020) identified an additional patient with autism spectrum disorder and a de novo heterozygous mutation (E689X; 610528.0012) in the CHD8 gene by trio whole-exome sequencing. Functional studies were not performed. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
|
|
Lee et al. (2020) reported 14-year-old female monozygotic twins with a congenital myasthenic syndrome (see, e.g., 601462) with a de novo c.1732C-T transition (NM_001170629) in the CHD8 gene, resulting in an R578C substitution at a highly conserved residue in the glutamine-rich domain. The mutation was identified by whole-exome sequencing and confirmed by Sanger sequencing. The mutation was predicted to affect protein folding and interactions with CHD8 binding partners. The sibs' clinical features included myasthenia, muscle weakness, ptosis, macrocephaly, and overgrowth. They were assessed as having average school performance with slightly below average long-term retrieval and fluid reasoning skills. </p>
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</span>
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<div>
|
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
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</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
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<p>Nishiyama et al. (2004) found that development of Duplin -/- mouse embryos was arrested at gastrulation, with the embryos manifesting massive apoptosis. In contrast, Duplin +/- mice appeared normal and were fertile. Expression of beta-catenin target genes was not increased in Duplin -/- embryos, suggesting that the lack of Duplin did not result in constitutive activation of Wnt signaling during embryogenesis. </p><p>Sugathan et al. (2014) found that knockdown of chd8 expression in zebrafish resulted in macrocephaly, likely caused by disturbed neuronal proliferation at early developmental stages. </p><p>Katayama et al. (2016) demonstrated that mice heterozygous for Chd8 mutations manifest ASD-like behavioral characteristics including increased anxiety, repetitive behavior, and altered social behavior. CHD8 haploinsufficiency did not result in prominent changes in the expression of a few specific genes but instead gave rise to small but global changes in gene expression in the mouse brain, reminiscent of those in the brains of patients with ASD. Gene set enrichment analysis revealed that neurodevelopment was delayed in the mutant mouse embryos. Furthermore, reduced expression of CHD8 was associated with abnormal activation of RE-1 silencing transcription factor (REST; 600571), which suppresses the transcription of many neuronal genes. REST activation was also observed in the brains of humans with ASD, and CHD8 was found to interact physically with REST in the mouse brain. Katayama et al. (2016) concluded that their results were consistent with the notion that CHD8 haploinsufficiency is a highly penetrant risk factor for ASD, with disease pathogenesis probably resulting from a delay in neurodevelopment. </p><p>Kawamura et al. (2021) found that mice with Chd8 deletion in brain were born approximately at the expected mendelian ratio, but that they subsequently showed growth retardation and cerebellar hypoplasia, and most died before 3 weeks of age. Analysis of mice with cerebellar granule neuron progenitor (GNP)-specific deletion of Chd8 showed that cerebellar hypoplasia resulted from a GNP-autonomous defect induced by Chd8 loss. Chd8 regulated proliferation and differentiation of GNPs, and cerebellar hypoplasia associated with Chd8 ablation resulted from attenuated proliferation and premature differentiation of Chd8-deficient GNPs. Chd8 was also required for pre- and postsynaptic integrity of CGNs, as electrophysiologic analysis revealed reduction in both pre- and postsynaptic function in mice with GNP-specific deletion of Chd8. Behavioral tests showed that GNP-specific Chd8-deficient mice manifested a motor behavioral defect, but not ASD-related behaviors. Chd8 was essential for activation of neuronal gene expression during GNP differentiation, and Chd8 deficiency attenuated proliferative capacity of progenitor cells by inhibiting expression of cell-cycle regulators at the transcriptional level. By conferring an accessible chromatin landscape and transactivating genes, CHD8 promoted GNP differentiation and contributed to GNP development. </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>14 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 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</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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CHD8, SER62TER
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<br />
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SNP: rs1331026006,
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gnomAD: rs1331026006,
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ClinVar: RCV000032826
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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 55-month-old non-Hispanic white male with intellectual developmental disorder with autism and macrocephaly (IDDAM; 615032), O'Roak et al. (2012) identified a de novo heterozygous nonsense mutation in the CHD8 gene, a ser-to-ter substitution at codon 62 (S62X). The boy had a low verbal IQ of 75, nonverbal IQ of 78, and below average adaptive score of 80. His head circumference was 53 cm (z score = 1.0). </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 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</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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CHD8, 1-BP INS, T
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<br />
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SNP: rs2139484859,
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ClinVar: RCV000032827
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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 67-month-old non-Hispanic white male with intellectual developmental disorder with autism and macrocephaly (IDDAM; 615032), O'Roak et al. (2012) detected a heterozygous de novo 1-basepair insertion in the CHD8 gene that resulted in premature termination of the protein (tyr747 to ter; Y747X). The proband was nonverbal with extremely low verbal IQ of 25, nonverbal IQ of 38, and adaptive score of 57. His head circumference was 55 cm (z score = 2.0). He was diagnosed with cerebral palsy and was excessively clumsy and uncoordinated at 18 months. MRI/CT at 18 months was normal; EEG was normal at 24 months. The proband had a healthy 4-year-old sister. </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 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</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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CHD8, NT3519, A-G, -2
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<br />
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SNP: rs1594344233,
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ClinVar: RCV000032828, RCV001291274, RCV001555708
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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 96-month-old non-Hispanic white female with intellectual developmental disorder with autism and macrocephaly (IDDAM; 615032), O'Roak et al. (2012) detected a de novo heterozygous splice site mutation (3519-2A-G) in the helicase superfamily C-terminal (HELC) domain of the CHD8 gene. She had a verbal IQ of 47 and a nonverbal IQ of 41, with clinical range deficits in social responsiveness and adaptive skills. She had experienced a delay in phrased speech. Her head circumference was 55.2 (z score = 2.3). She had a history of antiepileptic and antibiotic medication use, but not of seizures. MRI and EEG at age 5 were normal. A 6-year-old sister was healthy with normal head circumference. </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 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CHD8, GLN1238TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397514551,
|
|
|
|
|
|
|
|
ClinVar: RCV000032829
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 8-year-old non-Hispanic white male with intellectual developmental disorder with autism and macrocephaly (IDDAM; 615032), O'Roak et al. (2012) detected a heterozygous de novo nonsense mutation in the CHD8 gene, gln1238 to ter (Q1238X). In addition to the CHD8 mutation, the patient also carried a CUBN (602997) de novo nonsense mutation and 2 inherited copy number variations. The patient had an extremely low verbal IQ of 20, nonverbal IQ of 34, and low adaptive score of 59. He had macrocephaly (z score = 2.62) and normal BMI. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CHD8, ARG1337TER
|
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|
|
|
|
<br />
|
|
|
|
SNP: rs397514552,
|
|
|
|
|
|
|
|
ClinVar: RCV000032830, RCV004700297
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 63-month-old non-Hispanic white male with intellectual developmental disorder with autism and macrocephaly (IDDAM; 615032), O'Roak et al. (2012) detected a heterozygous de novo substitution at codon 1337 of the CHD8 gene (arg1337 to ter, R1337X). The patient was 1 of 4 children born to the same parents and the third of 6 pregnancies (the mother's first and fourth pregnancies resulted in miscarriage within 13 weeks). Verbal IQ was low (79), nonverbal IQ average (92), and adaptive score low (58). His head circumference was 55.4 cm (z score = 2.5). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CHD8, 4-BP DEL, CTTC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1887639311,
|
|
|
|
|
|
|
|
ClinVar: RCV000032831, RCV005089332
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 12-year-old non-Hispanic white male with intellectual developmental disorder with autism and macrocephaly (IDDAM; 615032), O'Roak et al. (2012) identified a de novo heterozygous frameshift mutation in the CHD8 gene (Glu2103ArgfsTer3). The patient had a verbal IQ of 60, nonverbal IQ of 67, and adaptive score of 73. He was diagnosed as excessively clumsy and uncoordinated at age 3. The patient showed clinical range deficits in social responsiveness and elevation in anxious/depressed mood, and had a mixed expressive-receptive language disorder and pragmatic language disorder. He had chronic diarrhea from age 5 to 8 years. He had an abnormal EEG and seizures at age 12 years concurrent with a head injury. His head circumference was 58 cm (z score = 2.7). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CHD8, 2-BP DEL, CT
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1887627866,
|
|
|
|
|
|
|
|
ClinVar: RCV000032832
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 55-month-old non-Hispanic white female with intellectual developmental disorder with autism and macrocephaly (IDDAM; 615032), O'Roak et al. (2012) identified a heterozygous de novo frameshift mutation in the CHD8 gene, a 2-basepair deletion resulting in premature termination of the protein (Leu2120ProfsTer13). The patient also carried a de novo nonsense mutations in the ETFB gene (130410) and the IQGAP2 gene (605401). She had normative range verbal IQ of 90 and nonverbal IQ of 93, but low adaptive behavioral skills score of 59. She had a large head (z score = 2.40). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CHD8, 1-BP INS, T
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs751094013,
|
|
|
|
|
|
gnomAD: rs751094013,
|
|
|
|
|
|
ClinVar: RCV001374912, RCV002251588, RCV004550095, RCV005051899
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 16-year-old non-Hispanic white male with intellectual developmental disorder with autism and macrocephaly (IDDAM; 615032), O'Roak et al. (2012) identified a heterozygous de novo 1-basepair insertion of a T nucleotide in the CHD8 gene, resulting in frameshift and premature termination of the protein (Asn2371LysfsTer2). The patient had an extremely low verbal IQ of 6, nonverbal IQ of 19, and adaptive score of 39. His head circumference was 60.8 cm (z score = 3.0). Loss of language skills during early development and attention problems were reported. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CHD8, 3-BP DEL, GGT
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs774490485,
|
|
|
|
|
|
gnomAD: rs774490485,
|
|
|
|
|
|
ClinVar: RCV000032834, RCV003556095
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 13-year-old non-Hispanic white male with intellectual developmental disorder with autism and macrocephaly (IDDAM; 615032), O'Roak et al. (2012) identified a heterozygous de novo in-frame deletion of 3 nucleotides in the CHD8 gene resulting in deletion of histidine-2498 (His2498del). The patient had a verbal IQ of 84, nonverbal IQ of 98, and very low adaptive score of 66. His head circumference was 57 cm (z score = 1.6). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CHD8, 1-BP DUP, 6276A
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV001374912, RCV002251588, RCV004550095, RCV005051899
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 17-year-old boy with intellectual developmental disorder with autism and macrocephaly (IDDAM; 615032), Merner et al. (2016) identified a heterozygous 1-bp duplication (c.6276dupA, NM_020920.3) in the CHD8 gene, predicted to result in a frameshift and premature termination (Asn2092LysfsTer2). The mutation, which was identified by sequencing of the CHD8 gene, occurred de novo. The mutation was not present in the dbSNP and ExAC databases. CHD8 mRNA and protein expression was reduced in patient lymphoblastoid cell lines compared to controls. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CHD8, ARG1188TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1555314911,
|
|
|
|
|
|
|
|
ClinVar: RCV001171595, RCV002249752
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 16-year-old boy with intellectual developmental disorder with autism and macrocephaly (IDDAM; 615032), An et al. (2020) identified a de novo heterozygous c.3562C-T transition (c.3562C-T, NM_001170629.1) in exon 17 of the CHD8 gene, resulting in an arg1188-to-ter (R1188X) substitution. The mutation, which was found by next-generation sequencing of a panel of genes and confirmed by Sanger sequencing, was not identified in either parent. Functional studies were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CHD8, GLU689TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1555316331,
|
|
|
|
|
|
|
|
ClinVar: RCV002248472
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-year-old boy with intellectual developmental disorder with autism and macrocephaly (IDDAM; 615032), An et al. (2020) identified a de novo heterozygous c.2065C-A transversion (c.2065C-A, NM_001170629.1) in exon 8 of the CHD8 gene, resulting in a glu689-to-ter (E689X) substitution. The mutation, which was identified by trio whole-exome sequencing and confirmed by Sanger sequencing, was not identified in the parents. Functional studies were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CHD8, IVS24, G-A, -1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2139460816,
|
|
|
|
|
|
|
|
ClinVar: RCV002248473
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 11-year-old boy with intellectual developmental disorder with autism and macrocephaly (IDDAM; 615032), An et al. (2020) identified a de novo heterozygous c.4818-1G-A transition (c.4818-1G-A, NM_0011700629.1) in intron 24 the CHD8 gene, predicted to result in a splicing abnormality and skipping of exon 25. The mutation, which was found by next-generation sequencing of a panel of genes and confirmed by Sanger sequencing, was not identified in either parent. Functional studies were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CHD8, TYR1168ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2139469836,
|
|
|
|
|
|
|
|
ClinVar: RCV002248474
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 12-year-old boy with intellectual developmental disorder with autism and macrocephaly (IDDAM; 615032), An et al. (2020) identified a de novo heterozygous c.3502T-A transversion (c.3502T-A, NM_001170629.1) in exon 16 of the CHD8 gene, resulting in a tyr1168-to-asn (Y1168N) substitution. The mutation, which was identified by next-generation sequencing of a panel of genes and confirmed by Sanger sequencing, was not identified in either parent. Functional studies were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Sanders et al. (2012)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
An, Y., Zhang, L., Liu, W., Jiang, Y., Chen, X., Lan, X., Li, G., Hang, Q., Wang, J., Gusella, J. F., Du, Y., Shen, Y.
|
|
<strong>De novo variants in the helicase-C domain of CHD8 are associated with severe phenotypes including autism, language disability and overgrowth.</strong>
|
|
Hum. Genet. 139: 499-512, 2020.
|
|
|
|
|
|
[PubMed: 31980904]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00439-020-02115-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Batsukh, T., Pieper, L., Koszucka, A. M., von Velsen, N., Hoyer-Fender, S., Elbracht, M., Bergman, J. E. H., Hoefsloot, L. H., Pauli, S.
|
|
<strong>CHD8 interacts with CHD7, a protein which is mutated in CHARGE syndrome.</strong>
|
|
Hum. Molec. Genet. 19: 2858-2866, 2010.
|
|
|
|
|
|
[PubMed: 20453063]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddq189]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Douzgou, S., Liang, H. W., Metcalfe, K., Somarathi, S., Tischkowitz, M., Mohamed, W., Kini, U., McKee, S., Yates, L., Bertoli, M., Lynch, S. A., Holder, S., the Deciphering Developmental Disorders Study, Banka, S.
|
|
<strong>The clinical presentation caused by truncating CHD8 variants.</strong>
|
|
Clin. Genet. 96: 72-84, 2019.
|
|
|
|
|
|
[PubMed: 31001818]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/cge.13554]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gross, M. B.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 7/1/2021.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ishihara, K., Oshimura, M., Nakao, M.
|
|
<strong>CTCF-dependent chromatin insulator is linked to epigenetic remodeling.</strong>
|
|
Molec. Cell 23: 733-742, 2006.
|
|
|
|
|
|
[PubMed: 16949368]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.molcel.2006.08.008]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Katayama, Y., Nishiyama, M., Shoji, H., Ohkawa, Y., Kawamura, A., Sato, T., Suyama, M., Takumi, T., Miyakawa, T., Nakayama, K. I.
|
|
<strong>CHD8 haploinsufficiency results in autistic-like phenotypes in mice.</strong>
|
|
Nature 537: 675-679, 2016.
|
|
|
|
|
|
[PubMed: 27602517]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature19357]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kawamura, A., Katayama, Y., Kakegawa, W., Ino, D., Nishiyama, M., Yuzaki, M., Nakayama, K. I.
|
|
<strong>The autism-associated protein CHD8 is required for cerebellar development and motor function.</strong>
|
|
Cell Rep. 35: 108932, 2021.
|
|
|
|
|
|
[PubMed: 33826902]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.celrep.2021.108932]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kobayashi, M., Kishida, S., Fukui, A., Michiue, T., Miyamoto, Y., Okamoto, T., Yoneda, Y., Asashima, M., Kikuchi, A.
|
|
<strong>Nuclear localization of Duplin, a beta-catenin-binding protein, is essential for its inhibitory activity on the Wnt signaling pathway.</strong>
|
|
J. Biol. Chem. 277: 5816-5822, 2002.
|
|
|
|
|
|
[PubMed: 11744694]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M108433200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kunkel, G. R., Lisciandro, H. G., Winter, H. L.
|
|
<strong>The human chd8 gene is transcribed from two distant upstream promoters.</strong>
|
|
Biochem. Biophys. Res. Commun. 532: 190-194, 2020.
|
|
|
|
|
|
[PubMed: 32854944]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.bbrc.2020.08.051]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lee, C. Y., Petkova, M., Morales-Gonzalez, S., Gimber, N., Schmoranzer, J., Meisel, A., Bohmerle, W., Stenzel, W., Schuelke, M., Schwarz, J. M.
|
|
<strong>A spontaneous missense mutation in the chromodomain helicase DNA-binding protein 8 (CHD8) gene: a novel association with congenital myasthenic syndrome.</strong>
|
|
Neuropath. Appl. Neurobiol. 46: 588-601, 2020.
|
|
|
|
|
|
[PubMed: 32267004]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/nan.12617]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Merner, N., Forgeot d'Arc, B., Bell, S. C., Maussion, G., Peng, H., Gauthier, J., Crapper, L., Hamdan, F. F., Michaud, J. L., Mottron, L., Rouleau, G. A., Ernst, C.
|
|
<strong>A de novo frameshift mutation in chromodomain helicase DNA-binding domain 8 (CHD8): a case report and literature review.</strong>
|
|
Am. J. Med. Genet. 170A: 1225-1235, 2016.
|
|
|
|
|
|
[PubMed: 26789910]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.37566]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nagase, T., Kikuno, R., Nakayama, M., Hirosawa, M., Ohara, O.
|
|
<strong>Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</strong>
|
|
DNA Res. 7: 273-281, 2000.
|
|
|
|
|
|
[PubMed: 10997877]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/dnares/7.4.271]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Neale, B. M., Kou, Y., Liu, L., Ma'ayan, A., Samocha, K. E., Sabo, A., Lin, C.-F., Stevens, C., Wang, L.-S., Makarov, V., Polak, P., Yoon, S., and 47 others.
|
|
<strong>Patterns and rates of exonic de novo mutations in autism spectrum disorders.</strong>
|
|
Nature 485: 242-245, 2012.
|
|
|
|
|
|
[PubMed: 22495311]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature11011]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nishiyama, M., Nakayama, K., Tsunematsu, R., Tsukiyama, T., Kikuchi, A., Nakayama, K. I.
|
|
<strong>Early embryonic death in mice lacking the beta-catenin-binding protein Duplin.</strong>
|
|
Molec. Cell. Biol. 24: 8386-8394, 2004.
|
|
|
|
|
|
[PubMed: 15367660]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/MCB.24.19.8386-8394.2004]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
O'Roak, B. J., Deriziotis, P., Lee, C., Vives, L., Schwartz, J. J., Girirajan, S., Karakoc, E., Mackenzie, A. P., Ng, S. B., Baker, C., Rieder, M. J., Nickerson, D. A., Bernier, R., Fisher, S. E., Shendure, J., Eichler, E. E.
|
|
<strong>Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.</strong>
|
|
Nature Genet. 43: 585-589, 2011. Note: Erratum: Nature Genet. 44: 471 only, 2012.
|
|
|
|
|
|
[PubMed: 21572417]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.835]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
O'Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., Munson, J., Hiatt, J. B., and 14 others.
|
|
<strong>Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.</strong>
|
|
Science 338: 1619-1622, 2012.
|
|
|
|
|
|
[PubMed: 23160955]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1227764]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
O'Roak, B. J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B. P., Levy, R., Ko, A., Lee, C., Smith, J. D., Turner, E. H., Stanaway, I. B., and 11 others.
|
|
<strong>Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.</strong>
|
|
Nature 485: 246-250, 2012.
|
|
|
|
|
|
[PubMed: 22495309]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature10989]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ostrowski, P. J., Zachariou, A., Loveday, C., Beleza-Meireles, A., Bertoli, M., Dean, J., Douglas, A. G. L., Ellis, I., Foster, A., Graham, J. M., Hague, J., Hilhorst-Hofstee, Y., and 23 others.
|
|
<strong>The CHD8 overgrowth syndrome: a detailed evaluation of an emerging overgrowth phenotype in 27 patients.</strong>
|
|
Am. J. Med. Genet. 181C: 557-564, 2019.
|
|
|
|
|
|
[PubMed: 31721432]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.c.31749]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sakamoto, I., Kishida, S., Fukui, A., Kishida, M., Yamamoto, H., Hino, S., Michiue, T., Takada, S., Asashima, M., Kikuchi, A.
|
|
<strong>A novel beta-catenin-binding protein inhibits beta-catenin-dependent Tcf activation and axis formation.</strong>
|
|
J. Biol. Chem. 275: 32871-32878, 2000.
|
|
|
|
|
|
[PubMed: 10921920]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M004089200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sanders, S. J., Murtha, M. T., Gupta, A. R., Murdoch, J. D., Raubeson, M. J., Willsey, A. J., Ercan-Sencicek, A. G., DiLullo, N. M., Parikshak, N. N., Stein, J. L., Walker, M. F., Ober, G. T., and 18 others.
|
|
<strong>De novo mutations revealed by whole-exome sequencing are strongly associated with autism.</strong>
|
|
Nature 485: 237-241, 2012.
|
|
|
|
|
|
[PubMed: 22495306]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature10945]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sugathan, A., Biagioli, M., Golzio, C., Erdin, S., Blumenthal, I., Manavalan, P., Ragavendran, A., Brand, H., Lucente, D., Miles, J., Sheridan, S. D., Stortchevoi, A., Kellis, M., Haggarty, S. J., Katsanis, N., Gusella, J. F., Talkowski, M. E.
|
|
<strong>CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors.</strong>
|
|
Proc. Nat. Acad. Sci. 111: E4468-E4477, 2014.
|
|
|
|
|
|
[PubMed: 25294932]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.1405266111]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thompson, B. A., Tremblay, V., Lin, G., Bochar, D. A.
|
|
<strong>CHD8 is an ATP-dependent chromatin remodeling factor that regulates beta-catenin target genes.</strong>
|
|
Molec. Cell. Biol. 28: 3894-3904, 2008.
|
|
|
|
|
|
[PubMed: 18378692]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/MCB.00322-08]
|
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|
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|
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