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Entry
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- *611386 - ACTIVITY-DEPENDENT NEUROPROTECTOR HOMEOBOX; ADNP
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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">*611386</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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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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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/611386">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000101126;t=ENST00000621696" 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=23394" 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=611386" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000101126;t=ENST00000621696" 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_001282531,NM_001282532,NM_001347511,NM_015339,NM_181442,XM_011528747,XM_011528748,XM_047440074,XM_047440075,XM_047440076,XM_047440077,XM_047440078" 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_001282531" 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=611386" 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=09793&isoform_id=09793_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/ADNP" 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/3882289,5262627,12043937,12229217,13170288,24636245,31563503,50370285,60551123,119596017,119596018,189054502,542133157,542133159,768016784,1109303173,2217334925,2217334927,2217334930,2217334932,2217334934,2217334936,2462580050,2462580052,2462580054,2462580056,2462580058,2462580060,2462580062" 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/Q9H2P0" 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=23394" 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=ENSG00000101126;t=ENST00000621696" 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=ADNP" 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=ADNP" 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+23394" 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/ADNP" 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:23394" 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/23394" 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=chr20&hgg_gene=ENST00000621696.5&hgg_start=50888918&hgg_end=50931437&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:15766" 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:15766" 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/adnp" 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=611386[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=611386[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/ADNP/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/ENSG00000101126" 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=ADNP" 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=ADNP" 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=ADNP" 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=ADNP&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/PA24582" 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:15766" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1338758" 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/ADNP#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:1338758" 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/23394/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=23394" 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://zfin.org/ZDB-GENE-030131-6385" 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://reactome.org/content/query?q=ADNP&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 766824003<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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611386
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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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ACTIVITY-DEPENDENT NEUROPROTECTOR HOMEOBOX; ADNP
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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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ADNP1<br />
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KIAA0784
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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=ADNP" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ADNP</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/20/387?start=-3&limit=10&highlight=387">20q13.13</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr20:50888918-50931437&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'})">20:50,888,918-50,931,437</a> </span>
|
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</em>
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
|
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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">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</div>
|
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<div>
|
|
<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>
|
|
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">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/20/387?start=-3&limit=10&highlight=387">
|
|
20q13.13
|
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</a>
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
Helsmoortel-van der Aa syndrome
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/615873"> 615873 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
|
<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">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/611386" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/611386" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<p>ADNP is a homeodomain-containing zinc finger protein with transcription factor activity that is essential for brain formation (<a href="#5" class="mim-tip-reference" title="Gozes, I. <strong>Activity-dependent neuroprotective protein: from gene to drug candidate.</strong> Pharm. Ther. 114: 146-154, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17363064/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17363064</a>] [<a href="https://doi.org/10.1016/j.pharmthera.2007.01.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17363064">Gozes, 2007</a>; <a href="#8" class="mim-tip-reference" title="Mandel, S., Rechavi, G., Gozes, I. <strong>Activity-dependent neuroprotective protein (ADNP) differentially interacts with chromatin to regulate genes essential for embryogenesis.</strong> Dev. Biol. 303: 814-824, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17222401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17222401</a>] [<a href="https://doi.org/10.1016/j.ydbio.2006.11.039" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17222401">Mandel et al., 2007</a>). ADNP interacts with components of the BAF complex, the eukaryotic equivalent of the SWI/SNF complex in yeast that is involved in the regulation of gene expression (summary by <a href="#6" class="mim-tip-reference" title="Helsmoortel, C., Vulto-van Silfhout, A. T., Coe, B. P., Vandeweyer, G., Rooms, L., van den Ende, J., Schuurs-Hoeijmakers, J. H. M., Marcelis, C. L., Willemsen, M. H., Vissers, L. E. L. M., Yntema, H. G., Bakshi, M., and 13 others. <strong>A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP.</strong> Nature Genet. 46: 380-384, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24531329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24531329</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24531329[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2899" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24531329">Helsmoortel et al., 2014</a>). See, e.g., ARID1A (<a href="/entry/603024">603024</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=24531329+17363064+17222401" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By screening for cDNAs encoding large proteins expressed in brain, <a href="#9" class="mim-tip-reference" title="Nagase, T., Ishikawa, K., Suyama, M., Kikuno, R., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. <strong>Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</strong> DNA Res. 5: 277-286, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9872452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9872452</a>] [<a href="https://doi.org/10.1093/dnares/5.5.277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9872452">Nagase et al. (1998)</a> cloned ADNP, which they called KIAA0784. The predicted protein contains 1,073 amino acids. RT-PCR ELISA showed ubiquitous expression of ADNP, with highest levels in brain and ovary, followed by heart, lung, kidney, and testis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9872452" 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 screening a fetal brain cDNA library with mouse Adnp, <a href="#14" class="mim-tip-reference" title="Zamostiano, R., Pinhasov, A., Gelber, E., Steingart, R. A., Seroussi, E., Giladi, E., Bassan, M., Wollman, Y., Eyre, H. J., Mulley, J. C., Brenneman, D. E., Gozes, I. <strong>Cloning and characterization of the human activity-dependent neuroprotective protein.</strong> J. Biol. Chem. 276: 708-714, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11013255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11013255</a>] [<a href="https://doi.org/10.1074/jbc.M007416200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11013255">Zamostiano et al. (2001)</a> cloned human ADNP. The predicted 1,102-amino acid protein has 9 zinc finger motifs, a proline-rich region, a bipartite nuclear localization signal, a partial homeobox domain, a glutaredoxin (GLRX; <a href="/entry/600443">600443</a>) active site, and a leucine-rich nuclear export sequence. Northern blot analysis revealed ubiquitous expression of a 5.5-kb transcript, with highest levels in heart, skeletal muscle, kidney, and placenta. Within brain, expression was highest in cerebellum and cortex. Expression of ADNP was increased in tumor tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11013255" 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 fluorescence-tagged protein, <a href="#7" class="mim-tip-reference" title="Mandel, S., Gozes, I. <strong>Activity-dependent neuroprotective protein constitutes a novel element in the SWI/SNF chromatin remodeling complex.</strong> J. Biol. Chem. 282: 34448-34456, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17878164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17878164</a>] [<a href="https://doi.org/10.1074/jbc.M704756200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17878164">Mandel and Gozes (2007)</a> found that ADNP localized to the nucleus of transfected HEK293 cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17878164" 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="Zamostiano, R., Pinhasov, A., Gelber, E., Steingart, R. A., Seroussi, E., Giladi, E., Bassan, M., Wollman, Y., Eyre, H. J., Mulley, J. C., Brenneman, D. E., Gozes, I. <strong>Cloning and characterization of the human activity-dependent neuroprotective protein.</strong> J. Biol. Chem. 276: 708-714, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11013255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11013255</a>] [<a href="https://doi.org/10.1074/jbc.M007416200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11013255">Zamostiano et al. (2001)</a> found that downregulation of ADNP by antisense oligonucleotides upregulated p53 (TP53; <a href="/entry/191170">191170</a>) and reduced the viability of intestinal cancer cells by 90%. They proposed that ADNP is involved in maintaining cell survival, possibly by modulating p53. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11013255" 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 peptide digestion followed by mass spectrometric analysis of HEK293 cell immunoprecipitates, <a href="#7" class="mim-tip-reference" title="Mandel, S., Gozes, I. <strong>Activity-dependent neuroprotective protein constitutes a novel element in the SWI/SNF chromatin remodeling complex.</strong> J. Biol. Chem. 282: 34448-34456, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17878164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17878164</a>] [<a href="https://doi.org/10.1074/jbc.M704756200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17878164">Mandel and Gozes (2007)</a> found that fluorescence-tagged ADNP interacted with BRG1 (SMARCA4; <a href="/entry/603254">603254</a>), BAF250A (ARID1A; <a href="/entry/603024">603024</a>), and BAF170 (SMARCC2; <a href="/entry/601734">601734</a>), which are components of the SWI/SNF chromatin remodeling complex. Domain analysis showed that the C-terminal domain of ADNP was required for its interaction with SWI/SNF proteins. Short hairpin RNAs that knocked down ADNP expression to 80%, but not to 50%, resulted in microtubule reorganization and changes in cell morphology, with reduced formation of cell processes and reduced cell number. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17878164" 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 quantitative RT-PCR, <a href="#4" class="mim-tip-reference" title="Dresner, E., Agam, G., Gozes, I. <strong>Activity-dependent neuroprotective protein (ADNP) expression level is correlated with the expression of the sister protein ADNP2: deregulation in schizophrenia.</strong> Europ. Neuropsychopharmacol. 21: 355-361, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20598862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20598862</a>] [<a href="https://doi.org/10.1016/j.euroneuro.2010.06.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20598862">Dresner et al. (2011)</a> found a high correlation between expression of ADNP2 (<a href="/entry/617422">617422</a>) and ADNP in postmortem normal human hippocampal specimens. This correlation was significantly reduced in hippocampus of schizophrenia patients, mirroring a disease-associated increase in ADNP2 transcripts. The correlation between ADNP2 and ADNP mRNA levels remained relatively higher in cortex of schizophrenia patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20598862" 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="#10" class="mim-tip-reference" title="Ostapcuk, V., Mohn, F., Carl, S. H., Basters, A., Hess, D., Iesmantavicius, V., Lampersberger, L., Flemr, M., Pandey, A., Thoma, N. H., Betschinger, J., Buhler, M. <strong>Activity-dependent neuroprotective protein recruits HP1 and CHD4 to control lineage-specifying genes.</strong> Nature 557: 739-743, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29795351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29795351</a>] [<a href="https://doi.org/10.1038/s41586-018-0153-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29795351">Ostapcuk et al. (2018)</a> showed that ADNP interacts with the chromatin remodeler CHD4 (<a href="/entry/603277">603277</a>) and the chromatin architectural protein HP1 (<a href="/entry/604478">604478</a>) to form a stable complex, which they referred to as ChAHP. Besides mediating complex assembly, ADNP recognizes DNA motifs that specify binding of ChAHP to euchromatin. Genetic ablation of ChAHP components in mouse embryonic stem cells resulted in spontaneous differentiation concomitant with premature activation of lineage-specific genes and in a failure to differentiate towards the neuronal lineage. Molecularly, ChAHP-mediated repression is fundamentally different from canonical HP1-mediated silencing: HP1 proteins, in conjunction with histone H3 lysine-9 trimethylation (H3K9me3), are thought to assemble broad heterochromatin domains that are refractory to transcription. ChAHP-mediated repression, however, acts in a locally restricted manner by establishing inaccessible chromatin around its DNA-binding sites and does not depend on H3K9me3-modified nucleosomes. <a href="#10" class="mim-tip-reference" title="Ostapcuk, V., Mohn, F., Carl, S. H., Basters, A., Hess, D., Iesmantavicius, V., Lampersberger, L., Flemr, M., Pandey, A., Thoma, N. H., Betschinger, J., Buhler, M. <strong>Activity-dependent neuroprotective protein recruits HP1 and CHD4 to control lineage-specifying genes.</strong> Nature 557: 739-743, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29795351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29795351</a>] [<a href="https://doi.org/10.1038/s41586-018-0153-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29795351">Ostapcuk et al. (2018)</a> concluded that their results revealed that ADNP, via the recruitment of HP1 and CHD4, regulates the expression of genes that are crucial for maintaining distinct cellular states and assures accurate cell fate decisions upon external cues. Such a general role of ChAHP in governing cell fate plasticity may explain why ADNP mutations affect several organs and body functions and contribute to cancer progression. <a href="#10" class="mim-tip-reference" title="Ostapcuk, V., Mohn, F., Carl, S. H., Basters, A., Hess, D., Iesmantavicius, V., Lampersberger, L., Flemr, M., Pandey, A., Thoma, N. H., Betschinger, J., Buhler, M. <strong>Activity-dependent neuroprotective protein recruits HP1 and CHD4 to control lineage-specifying genes.</strong> Nature 557: 739-743, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29795351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29795351</a>] [<a href="https://doi.org/10.1038/s41586-018-0153-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29795351">Ostapcuk et al. (2018)</a> found that the integrity of the ChAHP complex is disrupted by nonsense mutations identified in patients with Helsmoortel-Van der Aa syndrome (<a href="/entry/615873">615873</a>), and this could be rescued by aminoglycosides that suppress translation termination. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29795351" 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="Zamostiano, R., Pinhasov, A., Gelber, E., Steingart, R. A., Seroussi, E., Giladi, E., Bassan, M., Wollman, Y., Eyre, H. J., Mulley, J. C., Brenneman, D. E., Gozes, I. <strong>Cloning and characterization of the human activity-dependent neuroprotective protein.</strong> J. Biol. Chem. 276: 708-714, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11013255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11013255</a>] [<a href="https://doi.org/10.1074/jbc.M007416200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11013255">Zamostiano et al. (2001)</a> determined that the ADNP gene contains 5 exons and spans 40.6 kb. The last 3 exons are translated (<a href="#6" class="mim-tip-reference" title="Helsmoortel, C., Vulto-van Silfhout, A. T., Coe, B. P., Vandeweyer, G., Rooms, L., van den Ende, J., Schuurs-Hoeijmakers, J. H. M., Marcelis, C. L., Willemsen, M. H., Vissers, L. E. L. M., Yntema, H. G., Bakshi, M., and 13 others. <strong>A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP.</strong> Nature Genet. 46: 380-384, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24531329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24531329</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24531329[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2899" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24531329">Helsmoortel et al., 2014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=24531329+11013255" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using FISH, <a href="#14" class="mim-tip-reference" title="Zamostiano, R., Pinhasov, A., Gelber, E., Steingart, R. A., Seroussi, E., Giladi, E., Bassan, M., Wollman, Y., Eyre, H. J., Mulley, J. C., Brenneman, D. E., Gozes, I. <strong>Cloning and characterization of the human activity-dependent neuroprotective protein.</strong> J. Biol. Chem. 276: 708-714, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11013255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11013255</a>] [<a href="https://doi.org/10.1074/jbc.M007416200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11013255">Zamostiano et al. (2001)</a> mapped the ADNP gene to chromosome 20q12-q13.2, a region frequently amplified in neoplasias and associated with aggressive tumor growth. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11013255" 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 10 unrelated patients with Helsmoortel-Van der Aa syndrome (HVDAS; <a href="/entry/615873">615873</a>), <a href="#6" class="mim-tip-reference" title="Helsmoortel, C., Vulto-van Silfhout, A. T., Coe, B. P., Vandeweyer, G., Rooms, L., van den Ende, J., Schuurs-Hoeijmakers, J. H. M., Marcelis, C. L., Willemsen, M. H., Vissers, L. E. L. M., Yntema, H. G., Bakshi, M., and 13 others. <strong>A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP.</strong> Nature Genet. 46: 380-384, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24531329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24531329</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24531329[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2899" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24531329">Helsmoortel et al. (2014)</a> identified 9 different de novo heterozygous truncating mutations in the ADNP gene (see, e.g., <a href="#0001">611386.0001</a>-<a href="#0005">611386.0005</a>). The initial mutations were found by whole-exome sequencing, whereas additional mutations were found by direct analysis of the ADNP gene. The patients with MRD28 were ascertained from several cohorts totaling 5,776 unrelated patients with intellectual disability and/or autism spectrum disorder (ASD), thus accounting for 0.17% of these patients. All of the mutations occurred at the 3-prime end of the last exon of the ADNP gene and were predicted to result in the loss of at least the last 166 C-terminal residues, with escape from nonsense-mediated mRNA decay. Several of the mutations clustered in the stem of the same short hairpin, suggesting that the mutations may have resulted from a DNA-repair defect in this region. Available cells from 4 patients showed significantly increased levels of mutant mRNA compared to wildtype, suggesting deregulation of a negative expression feedback loop. <a href="#6" class="mim-tip-reference" title="Helsmoortel, C., Vulto-van Silfhout, A. T., Coe, B. P., Vandeweyer, G., Rooms, L., van den Ende, J., Schuurs-Hoeijmakers, J. H. M., Marcelis, C. L., Willemsen, M. H., Vissers, L. E. L. M., Yntema, H. G., Bakshi, M., and 13 others. <strong>A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP.</strong> Nature Genet. 46: 380-384, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24531329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24531329</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24531329[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2899" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24531329">Helsmoortel et al. (2014)</a> noted that mutations in other SWI/SNF components of the BAF complex, such as SMARCB1 (<a href="/entry/601607">601607</a>) and ARID1B (<a href="/entry/614556">614556</a>), have been identified in patients with intellectual disability, and hypothesized that the ADNP mutations cause a dominant-negative effect on the recruitment of the BAF complex, resulting in deregulation of gene expression and a disruption of neuronal processes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24531329" 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 4 patients with intellectual disability and varying syndromic features, the <a href="#3" class="mim-tip-reference" title="Deciphering Developmental Disorders Study. <strong>Large-scale discovery of novel genetic causes of developmental disorders.</strong> Nature 519: 223-228, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25533962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25533962</a>] [<a href="https://doi.org/10.1038/nature14135" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25533962">Deciphering Developmental Disorders Study (2015)</a> identified 3 de novo heterozygous mutations in the ADNP gene (<a href="#0006">611386.0006</a>-<a href="#0008">611386.0008</a>). Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25533962" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Van Dijck, A., Vulto-van Silfhout, A. T., Cappuyns, E., van der Werf,, I M., Mancini, G. M., Tzschach, A., Bernier, R., Gozes, I., Eichler, E. E., Romano, C., Lindstrand, A., Nordgren, A., and 9 others. <strong>Clinical presentation of a complex neurodevelopmental disorder caused by mutations in ADNP.</strong> Biol. Psychiatry 85: 287-297, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29724491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29724491</a>] [<a href="https://doi.org/10.1016/j.biopsych.2018.02.1173" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29724491">Van Dijck et al. (2019)</a> reported the mutations in the ADNP gene in a worldwide cohort of 78 individuals with HVDAS, some of whom had previously been reported. The patients ranged in age from 1 to 40 years. There were no reports of consanguinity or affected sibs. Forty-six unique mutations were identified, of which 25 were nonsense and 21 were frameshift. Forty-three of the mutations were located in the last exon of the ADNP gene. Some mutations indicated mutation hotspots (see, e.g., <a href="#0005">611386.0005</a>, <a href="#0009">611386.0009</a>, <a href="#0010">611386.0010</a>). Sixty-eight mutations were confirmed to be de novo, 8 mutations were of unknown inheritance, and 2 C-terminal mutations were inherited. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29724491" 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="Bend, E. G., Aref-Eshghi, E., Everman, D. B., Rogers, R. C., Cathey, S. S., Prijoles, E. J., Lyons, M. J., Davis, H., Clarkson, K., Gripp, K. W., Li, D., Bhoj, E., and 12 others. <strong>Gene domain-specific DNA methylation episignatures highlight distinct molecular entities of ADNP syndrome.</strong> Clin. Epigenet. 11: 64, 2019. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31029150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31029150</a>] [<a href="https://doi.org/10.1186/s13148-019-0658-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31029150">Bend et al. (2019)</a> performed genomewide DNA methylation analysis on peripheral blood DNA from 22 patients with HVDAS and identified 2 distinct episignatures caused by mutation in the ADNP gene. The first episignature (epi-ADNP-1) included approximately 6,000 mostly hypomethylated CpGs, and the second (epi-ADNP-2) included approximately 1,000 predominantly hypermethylated CpGs. The episignatures correlated with the location of the mutations, with epi-ADNP-1 mutations located outside nucleotides 2000 and 2340, and epi-ADNP-2 mutations located between nucleotides 2000 and 2340. The episignatures were enriched for genes involved in neuronal system development and function. <a href="#1" class="mim-tip-reference" title="Bend, E. G., Aref-Eshghi, E., Everman, D. B., Rogers, R. C., Cathey, S. S., Prijoles, E. J., Lyons, M. J., Davis, H., Clarkson, K., Gripp, K. W., Li, D., Bhoj, E., and 12 others. <strong>Gene domain-specific DNA methylation episignatures highlight distinct molecular entities of ADNP syndrome.</strong> Clin. Epigenet. 11: 64, 2019. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31029150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31029150</a>] [<a href="https://doi.org/10.1186/s13148-019-0658-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31029150">Bend et al. (2019)</a> showed that the DNA methylation signatures could aid in diagnosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31029150" 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="#2" class="mim-tip-reference" title="Breen, M. S., Garg, P., Tang, L., Mendonca, D., Levy, T., Barbosa, M., Arnett, A. B., Kurtz-Nelson, E., Agolini, E., Battaglia, A., Chiocchetti, A. G., Freitag, C. M., and 17 others. <strong>Episignatures stratifying Helsmoortel-Van Der Aa syndrome show modest correlation with phenotype.</strong> Am. J. Hum. Genet. 107: 555-563, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32758449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32758449</a>] [<a href="https://doi.org/10.1016/j.ajhg.2020.07.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32758449">Breen et al. (2020)</a> evaluated gene expression in 17 individuals with HVDAS and 19 controls to determine if gene expression changes were predictable based on methylation status. Profound alterations in corresponding gene expression profiles were not observed. The absence of correlation between methylation and gene expression signatures and clinical manifestations led <a href="#2" class="mim-tip-reference" title="Breen, M. S., Garg, P., Tang, L., Mendonca, D., Levy, T., Barbosa, M., Arnett, A. B., Kurtz-Nelson, E., Agolini, E., Battaglia, A., Chiocchetti, A. G., Freitag, C. M., and 17 others. <strong>Episignatures stratifying Helsmoortel-Van Der Aa syndrome show modest correlation with phenotype.</strong> Am. J. Hum. Genet. 107: 555-563, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32758449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32758449</a>] [<a href="https://doi.org/10.1016/j.ajhg.2020.07.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32758449">Breen et al. (2020)</a> to caution against making phenotypic assumptions based on the blood-based methylation profile. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32758449" 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="#2" class="mim-tip-reference" title="Breen, M. S., Garg, P., Tang, L., Mendonca, D., Levy, T., Barbosa, M., Arnett, A. B., Kurtz-Nelson, E., Agolini, E., Battaglia, A., Chiocchetti, A. G., Freitag, C. M., and 17 others. <strong>Episignatures stratifying Helsmoortel-Van Der Aa syndrome show modest correlation with phenotype.</strong> Am. J. Hum. Genet. 107: 555-563, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32758449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32758449</a>] [<a href="https://doi.org/10.1016/j.ajhg.2020.07.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32758449">Breen et al. (2020)</a> found that patients with class I mutations (located outside nucleotides 2000 and 2340) and class II mutations (located between nucleotides 2000 and 2340) had similar frequencies of impaired intellectual development, language impairment, attention-deficit hyperactivity disorder, and other medical problems. Individuals with class II mutations had a significantly longer delay in first walking independently, a higher prevalence of ASD, and a tendency towards increased self-injurious behavior. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32758449" 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="#12" class="mim-tip-reference" title="Pinhasov, A., Mandel, S., Torchinsky, A., Giladi, E., Pittel, Z., Goldsweig, A. M., Servoss, S. J., Brenneman, D. E., Gozes, I. <strong>Activity-dependent neuroprotective protein: a novel gene essential for brain formation.</strong> Brain Res. Dev. Brain Res. 144: 83-90, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12888219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12888219</a>] [<a href="https://doi.org/10.1016/s0165-3806(03)00162-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12888219">Pinhasov et al. (2003)</a> found that Adnp deletion in mice was embryonic lethal. Adnp -/- mice showed failure of cranial neural tube closure, increased Oct4 (POU5F1; <a href="/entry/164177">164177</a>) expression, and absence of Pax6 (<a href="/entry/607108">607108</a>) expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12888219" 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 microarray analysis, <a href="#8" class="mim-tip-reference" title="Mandel, S., Rechavi, G., Gozes, I. <strong>Activity-dependent neuroprotective protein (ADNP) differentially interacts with chromatin to regulate genes essential for embryogenesis.</strong> Dev. Biol. 303: 814-824, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17222401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17222401</a>] [<a href="https://doi.org/10.1016/j.ydbio.2006.11.039" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17222401">Mandel et al. (2007)</a> found that knockout of Adnp in mice upregulated genes involved in lipid transport, lytic vacuoles, and coagulation and downregulated genes involved in regulation of transcription, organogenesis, and neurogenesis. Promoter analysis revealed that genes upregulated by Adnp knockout were enriched in Pparg (<a href="/entry/601487">601487</a>)-, Hnf4 (HNF4A; <a href="/entry/600281">600281</a>)-, and Hnf1 (TCF1; <a href="/entry/142410">142410</a>)-binding sites, whereas downregulated genes were enriched in Zf5 (ZFP161; <a href="/entry/602126">602126</a>)- and E2f (E2F1; <a href="/entry/189971">189971</a>)-binding sites. Chromatin immunoprecipitation, bioinformatic, and coimmunoprecipitation analyses showed that Adnp bound chromatin and interacted with heterochromatin-1-alpha (CBX5; <a href="/entry/604478">604478</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17222401" 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">rs587777522 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777522;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=rs587777522" 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=rs587777522" 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=RCV000128574 OR RCV000485997 OR RCV001526522 OR RCV004019727" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000128574, RCV000485997, RCV001526522, RCV004019727" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000128574...</a>
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<p>In 2 unrelated children with Helsmoortel-Van der Aa syndrome (HVDAS; <a href="/entry/615873">615873</a>), <a href="#6" class="mim-tip-reference" title="Helsmoortel, C., Vulto-van Silfhout, A. T., Coe, B. P., Vandeweyer, G., Rooms, L., van den Ende, J., Schuurs-Hoeijmakers, J. H. M., Marcelis, C. L., Willemsen, M. H., Vissers, L. E. L. M., Yntema, H. G., Bakshi, M., and 13 others. <strong>A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP.</strong> Nature Genet. 46: 380-384, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24531329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24531329</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24531329[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2899" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24531329">Helsmoortel et al. (2014)</a> identified a de novo heterozygous 4-bp deletion (c.2491_2394delTTAA) in exon 5 of the ADNP gene, resulting in a frameshift and premature termination (Lys831IlefsTer81). The mutation, which was found by targeted analysis of the ADNP gene in both patients, was not present in the 1000 Genomes Project or Exome Sequencing Project databases, or in 1,728 unaffected individuals or 192 Belgian chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24531329" 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">rs587777523 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777523;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=rs587777523" 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=rs587777523" 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=RCV000128575 OR RCV000255626 OR RCV002312954" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000128575, RCV000255626, RCV002312954" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000128575...</a>
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<p>In a Belgian child with Helsmoortel-Van der Aa syndrome (HVDAS; <a href="/entry/615873">615873</a>), <a href="#6" class="mim-tip-reference" title="Helsmoortel, C., Vulto-van Silfhout, A. T., Coe, B. P., Vandeweyer, G., Rooms, L., van den Ende, J., Schuurs-Hoeijmakers, J. H. M., Marcelis, C. L., Willemsen, M. H., Vissers, L. E. L. M., Yntema, H. G., Bakshi, M., and 13 others. <strong>A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP.</strong> Nature Genet. 46: 380-384, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24531329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24531329</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24531329[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2899" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24531329">Helsmoortel et al. (2014)</a> identified a de novo heterozygous 4-bp deletion (c.2496_2499delTAAA) in exon 5 of the ADNP gene, resulting in a frameshift and premature termination (Asp832LysfsTer80). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the 1000 Genomes Project or Exome Sequencing Project databases, or in 1,728 unaffected individuals or 192 Belgian chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24531329" 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> rs587777524 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777524;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/rs587777524?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=rs587777524" 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=rs587777524" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a Belgian child with Helsmoortel-Van der Aa syndrome (HVDAS; <a href="/entry/615873">615873</a>), <a href="#6" class="mim-tip-reference" title="Helsmoortel, C., Vulto-van Silfhout, A. T., Coe, B. P., Vandeweyer, G., Rooms, L., van den Ende, J., Schuurs-Hoeijmakers, J. H. M., Marcelis, C. L., Willemsen, M. H., Vissers, L. E. L. M., Yntema, H. G., Bakshi, M., and 13 others. <strong>A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP.</strong> Nature Genet. 46: 380-384, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24531329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24531329</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24531329[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2899" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24531329">Helsmoortel et al. (2014)</a> identified a de novo heterozygous c.1211C-A transversion in exon 5 of the ADNP gene, resulting in a ser404-to-ter (S404X) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the 1000 Genomes Project or Exome Sequencing Project databases, or in 1,728 unaffected individuals or 192 Belgian chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24531329" 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 HELSMOORTEL-VAN DER AA SYNDROME</strong>
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ADNP, 1-BP DEL, 2808C
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587777525 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777525;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=rs587777525" 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=rs587777525" 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=RCV000128577" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000128577" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000128577</a>
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<p>In a Belgian child with Helsmoortel-Van der Aa syndrome (HVDAS; <a href="/entry/615873">615873</a>), <a href="#6" class="mim-tip-reference" title="Helsmoortel, C., Vulto-van Silfhout, A. T., Coe, B. P., Vandeweyer, G., Rooms, L., van den Ende, J., Schuurs-Hoeijmakers, J. H. M., Marcelis, C. L., Willemsen, M. H., Vissers, L. E. L. M., Yntema, H. G., Bakshi, M., and 13 others. <strong>A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP.</strong> Nature Genet. 46: 380-384, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24531329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24531329</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24531329[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2899" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24531329">Helsmoortel et al. (2014)</a> identified a de novo heterozygous 1-bp deletion (c.2808delC) in exon 5 of the ADNP gene, resulting in a frameshift and premature termination (Tyr936Ter). The mutation, which was found by targeted analysis of the ADNP gene, was not present in the 1000 Genomes Project or Exome Sequencing Project databases, or in 1,728 unaffected individuals or 192 Belgian chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24531329" 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 HELSMOORTEL-VAN DER AA SYNDROME</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> rs587777526 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777526;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/rs587777526?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=rs587777526" 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=rs587777526" 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=RCV000128578 OR RCV000190684 OR RCV000483727 OR RCV004739427" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000128578, RCV000190684, RCV000483727, RCV004739427" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000128578...</a>
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<p>In a Swedish child with Helsmoortel-Van der Aa syndrome (HVDAS; <a href="/entry/615873">615873</a>), <a href="#6" class="mim-tip-reference" title="Helsmoortel, C., Vulto-van Silfhout, A. T., Coe, B. P., Vandeweyer, G., Rooms, L., van den Ende, J., Schuurs-Hoeijmakers, J. H. M., Marcelis, C. L., Willemsen, M. H., Vissers, L. E. L. M., Yntema, H. G., Bakshi, M., and 13 others. <strong>A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP.</strong> Nature Genet. 46: 380-384, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24531329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24531329</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24531329[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2899" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24531329">Helsmoortel et al. (2014)</a> identified a de novo heterozygous c.2157C-G transversion in exon 5 of the ADNP gene, resulting in a tyr719-to-ter (Y719X) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the 1000 Genomes Project or Exome Sequencing Project databases, or in 1,728 unaffected individuals or 192 Belgian chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24531329" 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 whole-exome sequencing in a 6-year-old girl with HVDAS, <a href="#11" class="mim-tip-reference" title="Pescosolido, M. F., Schwede, M., Johnson Harrison, A., Schmidt, M., Gamsiz, E. D., Chen, W. S., Donahue, J. P., Shur, N., Jerskey, B. A., Phornphutkul, C., Morrow, E. M. <strong>Expansion of the clinical phenotype associated with mutations in activity-dependent neuroprotective protein.</strong> J. Med. Genet. 51: 587-589, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25057125/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25057125</a>] [<a href="https://doi.org/10.1136/jmedgenet-2014-102444" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25057125">Pescosolido et al. (2014)</a> identified a de novo heterozygous Y719X mutation in the ADNP gene. The mutation was confirmed by Sanger sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25057125" 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 worldwide cohort of 78 patients with HVDAS, <a href="#13" class="mim-tip-reference" title="Van Dijck, A., Vulto-van Silfhout, A. T., Cappuyns, E., van der Werf,, I M., Mancini, G. M., Tzschach, A., Bernier, R., Gozes, I., Eichler, E. E., Romano, C., Lindstrand, A., Nordgren, A., and 9 others. <strong>Clinical presentation of a complex neurodevelopmental disorder caused by mutations in ADNP.</strong> Biol. Psychiatry 85: 287-297, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29724491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29724491</a>] [<a href="https://doi.org/10.1016/j.biopsych.2018.02.1173" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29724491">Van Dijck et al. (2019)</a> identified the c.2157C-G mutation in 6 patients. A different mutation at the same nucleotide resulted in a Y719X substitution (<a href="#0009">611386.0009</a>), indicating that this is a mutation hotspot. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29724491" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 2 patients, a male and a female, with Helsmoortel-Van der Aa syndrome (HVDAS; <a href="/entry/615873">615873</a>), the <a href="#3" class="mim-tip-reference" title="Deciphering Developmental Disorders Study. <strong>Large-scale discovery of novel genetic causes of developmental disorders.</strong> Nature 519: 223-228, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25533962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25533962</a>] [<a href="https://doi.org/10.1038/nature14135" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25533962">Deciphering Developmental Disorders Study (2015)</a> identified a heterozygous de novo 4-bp deletion of TTTA nucleotides beginning at chromosome coordinate g.49,508,751 in the ADNP gene (chr20.49,508,751delTTTA, GRCh37), resulting in frameshift. The authors described the mutation as an indel (CTTTATTTA/CTTTA) between coordinates g.49,508,751 and g.49,508,760. Aside from global developmental delay, the patients had different clinical features. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25533962" 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">rs1135401808 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1135401808;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=rs1135401808" 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=rs1135401808" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a male patient (DECIPHER ID 258927) with intellectual disability, plagiocephaly, obesity, and inguinal hernia (HVDAS; <a href="/entry/615873">615873</a>), the <a href="#3" class="mim-tip-reference" title="Deciphering Developmental Disorders Study. <strong>Large-scale discovery of novel genetic causes of developmental disorders.</strong> Nature 519: 223-228, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25533962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25533962</a>] [<a href="https://doi.org/10.1038/nature14135" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25533962">Deciphering Developmental Disorders Study (2015)</a> identified a heterozygous de novo 1-bp insertion of a T at chromosome coordinate g.49,509,094 in the ADNP gene (chr20.49,509,094insT, GRCh37). The authors described the mutation as an indel (GT/GTT) between coordinates g.49,509,094 and g.49,509,097. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25533962" 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 male patient with Helsmoortel-Van der Aa syndrome (HVDAS; <a href="/entry/615873">615873</a>), the <a href="#3" class="mim-tip-reference" title="Deciphering Developmental Disorders Study. <strong>Large-scale discovery of novel genetic causes of developmental disorders.</strong> Nature 519: 223-228, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25533962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25533962</a>] [<a href="https://doi.org/10.1038/nature14135" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25533962">Deciphering Developmental Disorders Study (2015)</a> identified a heterozygous de novo 2-bp deletion of a TT at chromosome coordinate g.49,510,027 in the ADNP gene (chr20.49,510,027delTT). The authors described the mutation as an indel (CTTT/CT) between coordinates g.49,510,027 and g.49,510,031. The patient had global developmental delay, generalized neonatal hypotonia, bilateral ptosis, plagiocephaly, first-degree microtia, and respiratory distress. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25533962" 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=RCV000404317 OR RCV001265359 OR RCV004739651 OR RCV004975381" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000404317, RCV001265359, RCV004739651, RCV004975381" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000404317...</a>
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<p>From a worldwide cohort of 78 patients with Helsmoortel-Van der Aa syndrome (HVDAS; <a href="/entry/615873">615873</a>), <a href="#13" class="mim-tip-reference" title="Van Dijck, A., Vulto-van Silfhout, A. T., Cappuyns, E., van der Werf,, I M., Mancini, G. M., Tzschach, A., Bernier, R., Gozes, I., Eichler, E. E., Romano, C., Lindstrand, A., Nordgren, A., and 9 others. <strong>Clinical presentation of a complex neurodevelopmental disorder caused by mutations in ADNP.</strong> Biol. Psychiatry 85: 287-297, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29724491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29724491</a>] [<a href="https://doi.org/10.1016/j.biopsych.2018.02.1173" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29724491">Van Dijck et al. (2019)</a> identified a c.2157C-A transversion in the ADNP gene, resulting in a tyr719-to-ter (Y719X) substitution, in 3 patients. A different mutation at the same nucleotide resulted in a Y719X substitution (<a href="#0005">611386.0005</a>), indicating that this is a mutation hotspot. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29724491" 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>From a worldwide cohort of 78 patients with Helsmoortel-Van der Aa syndrome (HVDAS; <a href="/entry/615873">615873</a>), <a href="#13" class="mim-tip-reference" title="Van Dijck, A., Vulto-van Silfhout, A. T., Cappuyns, E., van der Werf,, I M., Mancini, G. M., Tzschach, A., Bernier, R., Gozes, I., Eichler, E. E., Romano, C., Lindstrand, A., Nordgren, A., and 9 others. <strong>Clinical presentation of a complex neurodevelopmental disorder caused by mutations in ADNP.</strong> Biol. Psychiatry 85: 287-297, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29724491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29724491</a>] [<a href="https://doi.org/10.1016/j.biopsych.2018.02.1173" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29724491">Van Dijck et al. (2019)</a> identified a 4-bp deletion in the ADNP gene (c.2496_2499delTAAA), resulting in a frameshift and premature termination (Asn832LysfsTer81), in 10 patients. The mutation had previously been identified in a patient by <a href="#6" class="mim-tip-reference" title="Helsmoortel, C., Vulto-van Silfhout, A. T., Coe, B. P., Vandeweyer, G., Rooms, L., van den Ende, J., Schuurs-Hoeijmakers, J. H. M., Marcelis, C. L., Willemsen, M. H., Vissers, L. E. L. M., Yntema, H. G., Bakshi, M., and 13 others. <strong>A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP.</strong> Nature Genet. 46: 380-384, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24531329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24531329</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24531329[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2899" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24531329">Helsmoortel et al. (2014)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=29724491+24531329" 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 HELSMOORTEL-VAN DER AA SYNDROME</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000170479 OR RCV000627402 OR RCV001249500 OR RCV002277322 OR RCV002426805" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000170479, RCV000627402, RCV001249500, RCV002277322, RCV002426805" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000170479...</a>
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<p>From a worldwide cohort of 78 patients with Helsmoortel-Van der Aa syndrome (HVDAS; <a href="/entry/615873">615873</a>), <a href="#13" class="mim-tip-reference" title="Van Dijck, A., Vulto-van Silfhout, A. T., Cappuyns, E., van der Werf,, I M., Mancini, G. M., Tzschach, A., Bernier, R., Gozes, I., Eichler, E. E., Romano, C., Lindstrand, A., Nordgren, A., and 9 others. <strong>Clinical presentation of a complex neurodevelopmental disorder caused by mutations in ADNP.</strong> Biol. Psychiatry 85: 287-297, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29724491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29724491</a>] [<a href="https://doi.org/10.1016/j.biopsych.2018.02.1173" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29724491">Van Dijck et al. (2019)</a> identified a 1-bp duplication (c.2156dupT) in the ADNP gene, resulting in a tyr719-to-ter (Y719X) substitution, in 8 patients. The authors identified 2 other mutations in the ADNP gene in patients with HVDAS that resulted in a Y719X substitution (see <a href="#0005">611386.0005</a> and <a href="#0009">611386.0009</a>). This mutation had previously been identified in a patient by <a href="#6" class="mim-tip-reference" title="Helsmoortel, C., Vulto-van Silfhout, A. T., Coe, B. P., Vandeweyer, G., Rooms, L., van den Ende, J., Schuurs-Hoeijmakers, J. H. M., Marcelis, C. L., Willemsen, M. H., Vissers, L. E. L. M., Yntema, H. G., Bakshi, M., and 13 others. <strong>A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP.</strong> Nature Genet. 46: 380-384, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24531329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24531329</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24531329[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2899" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24531329">Helsmoortel et al. (2014)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=29724491+24531329" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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Helsmoortel, C., Vulto-van Silfhout, A. T., Coe, B. P., Vandeweyer, G., Rooms, L., van den Ende, J., Schuurs-Hoeijmakers, J. H. M., Marcelis, C. L., Willemsen, M. H., Vissers, L. E. L. M., Yntema, H. G., Bakshi, M., and 13 others.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25057125/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25057125</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25057125" 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/10.1136/jmedgenet-2014-102444" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Pinhasov2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Pinhasov, A., Mandel, S., Torchinsky, A., Giladi, E., Pittel, Z., Goldsweig, A. M., Servoss, S. J., Brenneman, D. E., Gozes, I.
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<strong>Activity-dependent neuroprotective protein: a novel gene essential for brain formation.</strong>
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Brain Res. Dev. Brain Res. 144: 83-90, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12888219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12888219</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12888219" 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/s0165-3806(03)00162-7" target="_blank">Full Text</a>]
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<a id="13" class="mim-anchor"></a>
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<a id="Van Dijck2019" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Van Dijck, A., Vulto-van Silfhout, A. T., Cappuyns, E., van der Werf,, I M., Mancini, G. M., Tzschach, A., Bernier, R., Gozes, I., Eichler, E. E., Romano, C., Lindstrand, A., Nordgren, A., and 9 others.
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<strong>Clinical presentation of a complex neurodevelopmental disorder caused by mutations in ADNP.</strong>
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Biol. Psychiatry 85: 287-297, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29724491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29724491</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29724491" 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.biopsych.2018.02.1173" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="Zamostiano2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zamostiano, R., Pinhasov, A., Gelber, E., Steingart, R. A., Seroussi, E., Giladi, E., Bassan, M., Wollman, Y., Eyre, H. J., Mulley, J. C., Brenneman, D. E., Gozes, I.
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<strong>Cloning and characterization of the human activity-dependent neuroprotective protein.</strong>
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J. Biol. Chem. 276: 708-714, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11013255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11013255</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11013255" 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.M007416200" target="_blank">Full Text</a>]
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</p>
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</ol>
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<br />
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<a id="contributors" class="mim-anchor"></a>
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 02/24/2021
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Carol A. Bocchini - updated : 02/12/2021<br>Ada Hamosh - updated : 08/20/2018<br>Patricia A. Hartz - updated : 03/31/2017<br>Ada Hamosh - updated : 05/11/2015<br>Cassandra L. Kniffin - updated : 5/4/2015<br>Cassandra L. Kniffin - updated : 7/9/2014
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</span>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Paul J. Converse : 8/28/2007
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</span>
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<a id="editHistory" class="mim-anchor"></a>
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 02/25/2021
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 02/24/2021<br>carol : 02/12/2021<br>alopez : 08/20/2018<br>alopez : 03/31/2017<br>alopez : 03/31/2017<br>alopez : 05/11/2015<br>carol : 5/5/2015<br>mcolton : 5/4/2015<br>ckniffin : 5/4/2015<br>carol : 4/24/2015<br>carol : 3/26/2015<br>carol : 11/6/2014<br>carol : 7/10/2014<br>mcolton : 7/10/2014<br>ckniffin : 7/9/2014<br>mgross : 8/28/2007
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</span>
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<div class="container visible-print-block">
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 611386
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</span>
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</h3>
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<div>
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<h3>
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<span class="mim-font">
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ACTIVITY-DEPENDENT NEUROPROTECTOR HOMEOBOX; ADNP
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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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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<div>
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<h4>
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<span class="mim-font">
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ADNP1<br />
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KIAA0784
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</span>
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</h4>
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<br />
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: ADNP</em></strong>
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</span>
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</p>
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</div>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 766824003;
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</span>
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<strong>
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<em>
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Cytogenetic location: 20q13.13
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Genomic coordinates <span class="small">(GRCh38)</span> : 20:50,888,918-50,931,437 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<td rowspan="1">
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<span class="mim-font">
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20q13.13
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<td>
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<span class="mim-font">
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Helsmoortel-van der Aa syndrome
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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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615873
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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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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>ADNP is a homeodomain-containing zinc finger protein with transcription factor activity that is essential for brain formation (Gozes, 2007; Mandel et al., 2007). ADNP interacts with components of the BAF complex, the eukaryotic equivalent of the SWI/SNF complex in yeast that is involved in the regulation of gene expression (summary by Helsmoortel et al., 2014). See, e.g., ARID1A (603024). </p>
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<div>
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<br />
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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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<span class="mim-text-font">
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<p>By screening for cDNAs encoding large proteins expressed in brain, Nagase et al. (1998) cloned ADNP, which they called KIAA0784. The predicted protein contains 1,073 amino acids. RT-PCR ELISA showed ubiquitous expression of ADNP, with highest levels in brain and ovary, followed by heart, lung, kidney, and testis. </p><p>By screening a fetal brain cDNA library with mouse Adnp, Zamostiano et al. (2001) cloned human ADNP. The predicted 1,102-amino acid protein has 9 zinc finger motifs, a proline-rich region, a bipartite nuclear localization signal, a partial homeobox domain, a glutaredoxin (GLRX; 600443) active site, and a leucine-rich nuclear export sequence. Northern blot analysis revealed ubiquitous expression of a 5.5-kb transcript, with highest levels in heart, skeletal muscle, kidney, and placenta. Within brain, expression was highest in cerebellum and cortex. Expression of ADNP was increased in tumor tissues. </p><p>Using fluorescence-tagged protein, Mandel and Gozes (2007) found that ADNP localized to the nucleus of transfected HEK293 cells. </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>Zamostiano et al. (2001) found that downregulation of ADNP by antisense oligonucleotides upregulated p53 (TP53; 191170) and reduced the viability of intestinal cancer cells by 90%. They proposed that ADNP is involved in maintaining cell survival, possibly by modulating p53. </p><p>By peptide digestion followed by mass spectrometric analysis of HEK293 cell immunoprecipitates, Mandel and Gozes (2007) found that fluorescence-tagged ADNP interacted with BRG1 (SMARCA4; 603254), BAF250A (ARID1A; 603024), and BAF170 (SMARCC2; 601734), which are components of the SWI/SNF chromatin remodeling complex. Domain analysis showed that the C-terminal domain of ADNP was required for its interaction with SWI/SNF proteins. Short hairpin RNAs that knocked down ADNP expression to 80%, but not to 50%, resulted in microtubule reorganization and changes in cell morphology, with reduced formation of cell processes and reduced cell number. </p><p>By quantitative RT-PCR, Dresner et al. (2011) found a high correlation between expression of ADNP2 (617422) and ADNP in postmortem normal human hippocampal specimens. This correlation was significantly reduced in hippocampus of schizophrenia patients, mirroring a disease-associated increase in ADNP2 transcripts. The correlation between ADNP2 and ADNP mRNA levels remained relatively higher in cortex of schizophrenia patients. </p><p>Ostapcuk et al. (2018) showed that ADNP interacts with the chromatin remodeler CHD4 (603277) and the chromatin architectural protein HP1 (604478) to form a stable complex, which they referred to as ChAHP. Besides mediating complex assembly, ADNP recognizes DNA motifs that specify binding of ChAHP to euchromatin. Genetic ablation of ChAHP components in mouse embryonic stem cells resulted in spontaneous differentiation concomitant with premature activation of lineage-specific genes and in a failure to differentiate towards the neuronal lineage. Molecularly, ChAHP-mediated repression is fundamentally different from canonical HP1-mediated silencing: HP1 proteins, in conjunction with histone H3 lysine-9 trimethylation (H3K9me3), are thought to assemble broad heterochromatin domains that are refractory to transcription. ChAHP-mediated repression, however, acts in a locally restricted manner by establishing inaccessible chromatin around its DNA-binding sites and does not depend on H3K9me3-modified nucleosomes. Ostapcuk et al. (2018) concluded that their results revealed that ADNP, via the recruitment of HP1 and CHD4, regulates the expression of genes that are crucial for maintaining distinct cellular states and assures accurate cell fate decisions upon external cues. Such a general role of ChAHP in governing cell fate plasticity may explain why ADNP mutations affect several organs and body functions and contribute to cancer progression. Ostapcuk et al. (2018) found that the integrity of the ChAHP complex is disrupted by nonsense mutations identified in patients with Helsmoortel-Van der Aa syndrome (615873), and this could be rescued by aminoglycosides that suppress translation termination. </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>Zamostiano et al. (2001) determined that the ADNP gene contains 5 exons and spans 40.6 kb. The last 3 exons are translated (Helsmoortel et al., 2014). </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>Using FISH, Zamostiano et al. (2001) mapped the ADNP gene to chromosome 20q12-q13.2, a region frequently amplified in neoplasias and associated with aggressive tumor growth. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In 10 unrelated patients with Helsmoortel-Van der Aa syndrome (HVDAS; 615873), Helsmoortel et al. (2014) identified 9 different de novo heterozygous truncating mutations in the ADNP gene (see, e.g., 611386.0001-611386.0005). The initial mutations were found by whole-exome sequencing, whereas additional mutations were found by direct analysis of the ADNP gene. The patients with MRD28 were ascertained from several cohorts totaling 5,776 unrelated patients with intellectual disability and/or autism spectrum disorder (ASD), thus accounting for 0.17% of these patients. All of the mutations occurred at the 3-prime end of the last exon of the ADNP gene and were predicted to result in the loss of at least the last 166 C-terminal residues, with escape from nonsense-mediated mRNA decay. Several of the mutations clustered in the stem of the same short hairpin, suggesting that the mutations may have resulted from a DNA-repair defect in this region. Available cells from 4 patients showed significantly increased levels of mutant mRNA compared to wildtype, suggesting deregulation of a negative expression feedback loop. Helsmoortel et al. (2014) noted that mutations in other SWI/SNF components of the BAF complex, such as SMARCB1 (601607) and ARID1B (614556), have been identified in patients with intellectual disability, and hypothesized that the ADNP mutations cause a dominant-negative effect on the recruitment of the BAF complex, resulting in deregulation of gene expression and a disruption of neuronal processes. </p><p>In 4 patients with intellectual disability and varying syndromic features, the Deciphering Developmental Disorders Study (2015) identified 3 de novo heterozygous mutations in the ADNP gene (611386.0006-611386.0008). Functional studies were not performed. </p><p>Van Dijck et al. (2019) reported the mutations in the ADNP gene in a worldwide cohort of 78 individuals with HVDAS, some of whom had previously been reported. The patients ranged in age from 1 to 40 years. There were no reports of consanguinity or affected sibs. Forty-six unique mutations were identified, of which 25 were nonsense and 21 were frameshift. Forty-three of the mutations were located in the last exon of the ADNP gene. Some mutations indicated mutation hotspots (see, e.g., 611386.0005, 611386.0009, 611386.0010). Sixty-eight mutations were confirmed to be de novo, 8 mutations were of unknown inheritance, and 2 C-terminal mutations were inherited. </p><p>Bend et al. (2019) performed genomewide DNA methylation analysis on peripheral blood DNA from 22 patients with HVDAS and identified 2 distinct episignatures caused by mutation in the ADNP gene. The first episignature (epi-ADNP-1) included approximately 6,000 mostly hypomethylated CpGs, and the second (epi-ADNP-2) included approximately 1,000 predominantly hypermethylated CpGs. The episignatures correlated with the location of the mutations, with epi-ADNP-1 mutations located outside nucleotides 2000 and 2340, and epi-ADNP-2 mutations located between nucleotides 2000 and 2340. The episignatures were enriched for genes involved in neuronal system development and function. Bend et al. (2019) showed that the DNA methylation signatures could aid in diagnosis. </p><p>Breen et al. (2020) evaluated gene expression in 17 individuals with HVDAS and 19 controls to determine if gene expression changes were predictable based on methylation status. Profound alterations in corresponding gene expression profiles were not observed. The absence of correlation between methylation and gene expression signatures and clinical manifestations led Breen et al. (2020) to caution against making phenotypic assumptions based on the blood-based methylation profile. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Genotype/Phenotype Correlations</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Breen et al. (2020) found that patients with class I mutations (located outside nucleotides 2000 and 2340) and class II mutations (located between nucleotides 2000 and 2340) had similar frequencies of impaired intellectual development, language impairment, attention-deficit hyperactivity disorder, and other medical problems. Individuals with class II mutations had a significantly longer delay in first walking independently, a higher prevalence of ASD, and a tendency towards increased self-injurious behavior. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Pinhasov et al. (2003) found that Adnp deletion in mice was embryonic lethal. Adnp -/- mice showed failure of cranial neural tube closure, increased Oct4 (POU5F1; 164177) expression, and absence of Pax6 (607108) expression. </p><p>By microarray analysis, Mandel et al. (2007) found that knockout of Adnp in mice upregulated genes involved in lipid transport, lytic vacuoles, and coagulation and downregulated genes involved in regulation of transcription, organogenesis, and neurogenesis. Promoter analysis revealed that genes upregulated by Adnp knockout were enriched in Pparg (601487)-, Hnf4 (HNF4A; 600281)-, and Hnf1 (TCF1; 142410)-binding sites, whereas downregulated genes were enriched in Zf5 (ZFP161; 602126)- and E2f (E2F1; 189971)-binding sites. Chromatin immunoprecipitation, bioinformatic, and coimmunoprecipitation analyses showed that Adnp bound chromatin and interacted with heterochromatin-1-alpha (CBX5; 604478). </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>11 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 HELSMOORTEL-VAN DER AA SYNDROME</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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ADNP, 4-BP DEL, 2491TTAA
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<br />
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SNP: rs587777522,
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ClinVar: RCV000128574, RCV000485997, RCV001526522, RCV004019727
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 unrelated children with Helsmoortel-Van der Aa syndrome (HVDAS; 615873), Helsmoortel et al. (2014) identified a de novo heterozygous 4-bp deletion (c.2491_2394delTTAA) in exon 5 of the ADNP gene, resulting in a frameshift and premature termination (Lys831IlefsTer81). The mutation, which was found by targeted analysis of the ADNP gene in both patients, was not present in the 1000 Genomes Project or Exome Sequencing Project databases, or in 1,728 unaffected individuals or 192 Belgian chromosomes. </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 HELSMOORTEL-VAN DER AA SYNDROME</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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ADNP, 4-BP DEL, 2496TAAA
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<br />
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SNP: rs587777523,
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ClinVar: RCV000128575, RCV000255626, RCV002312954
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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 Belgian child with Helsmoortel-Van der Aa syndrome (HVDAS; 615873), Helsmoortel et al. (2014) identified a de novo heterozygous 4-bp deletion (c.2496_2499delTAAA) in exon 5 of the ADNP gene, resulting in a frameshift and premature termination (Asp832LysfsTer80). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the 1000 Genomes Project or Exome Sequencing Project databases, or in 1,728 unaffected individuals or 192 Belgian chromosomes. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0003 HELSMOORTEL-VAN DER AA SYNDROME</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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|
ADNP, SER404TER
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<br />
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SNP: rs587777524,
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gnomAD: rs587777524,
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ClinVar: RCV000128576
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</span>
|
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a Belgian child with Helsmoortel-Van der Aa syndrome (HVDAS; 615873), Helsmoortel et al. (2014) identified a de novo heterozygous c.1211C-A transversion in exon 5 of the ADNP gene, resulting in a ser404-to-ter (S404X) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the 1000 Genomes Project or Exome Sequencing Project databases, or in 1,728 unaffected individuals or 192 Belgian chromosomes. </p>
|
|
</span>
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|
</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 HELSMOORTEL-VAN DER AA SYNDROME</strong>
|
|
</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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|
|
|
ADNP, 1-BP DEL, 2808C
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<br />
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|
|
SNP: rs587777525,
|
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|
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|
|
ClinVar: RCV000128577
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Belgian child with Helsmoortel-Van der Aa syndrome (HVDAS; 615873), Helsmoortel et al. (2014) identified a de novo heterozygous 1-bp deletion (c.2808delC) in exon 5 of the ADNP gene, resulting in a frameshift and premature termination (Tyr936Ter). The mutation, which was found by targeted analysis of the ADNP gene, was not present in the 1000 Genomes Project or Exome Sequencing Project databases, or in 1,728 unaffected individuals or 192 Belgian chromosomes. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 HELSMOORTEL-VAN DER AA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ADNP, TYR719TER, 2157C-G
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587777526,
|
|
|
|
|
|
gnomAD: rs587777526,
|
|
|
|
|
|
ClinVar: RCV000128578, RCV000190684, RCV000483727, RCV004739427
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Swedish child with Helsmoortel-Van der Aa syndrome (HVDAS; 615873), Helsmoortel et al. (2014) identified a de novo heterozygous c.2157C-G transversion in exon 5 of the ADNP gene, resulting in a tyr719-to-ter (Y719X) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the 1000 Genomes Project or Exome Sequencing Project databases, or in 1,728 unaffected individuals or 192 Belgian chromosomes. </p><p>By whole-exome sequencing in a 6-year-old girl with HVDAS, Pescosolido et al. (2014) identified a de novo heterozygous Y719X mutation in the ADNP gene. The mutation was confirmed by Sanger sequencing. </p><p>In a worldwide cohort of 78 patients with HVDAS, Van Dijck et al. (2019) identified the c.2157C-G mutation in 6 patients. A different mutation at the same nucleotide resulted in a Y719X substitution (611386.0009), indicating that this is a mutation hotspot. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 HELSMOORTEL-VAN DER AA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ADNP, 4-BP DEL, TTTA
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000128575, RCV000255626, RCV002312954
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 patients, a male and a female, with Helsmoortel-Van der Aa syndrome (HVDAS; 615873), the Deciphering Developmental Disorders Study (2015) identified a heterozygous de novo 4-bp deletion of TTTA nucleotides beginning at chromosome coordinate g.49,508,751 in the ADNP gene (chr20.49,508,751delTTTA, GRCh37), resulting in frameshift. The authors described the mutation as an indel (CTTTATTTA/CTTTA) between coordinates g.49,508,751 and g.49,508,760. Aside from global developmental delay, the patients had different clinical features. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 HELSMOORTEL-VAN DER AA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ADNP, 1-BP INS, T
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1135401808,
|
|
|
|
|
|
|
|
ClinVar: RCV000170479, RCV000627402, RCV001249500, RCV002277322, RCV002426805
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a male patient (DECIPHER ID 258927) with intellectual disability, plagiocephaly, obesity, and inguinal hernia (HVDAS; 615873), the Deciphering Developmental Disorders Study (2015) identified a heterozygous de novo 1-bp insertion of a T at chromosome coordinate g.49,509,094 in the ADNP gene (chr20.49,509,094insT, GRCh37). The authors described the mutation as an indel (GT/GTT) between coordinates g.49,509,094 and g.49,509,097. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 HELSMOORTEL-VAN DER AA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ADNP, 2-BP DEL, TT
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1555810376,
|
|
|
|
|
|
|
|
ClinVar: RCV000170480
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a male patient with Helsmoortel-Van der Aa syndrome (HVDAS; 615873), the Deciphering Developmental Disorders Study (2015) identified a heterozygous de novo 2-bp deletion of a TT at chromosome coordinate g.49,510,027 in the ADNP gene (chr20.49,510,027delTT). The authors described the mutation as an indel (CTTT/CT) between coordinates g.49,510,027 and g.49,510,031. The patient had global developmental delay, generalized neonatal hypotonia, bilateral ptosis, plagiocephaly, first-degree microtia, and respiratory distress. </p>
|
|
</span>
|
|
</div>
|
|
|
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|
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 HELSMOORTEL-VAN DER AA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ADNP, TYR719TER, c.2157C-A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587777526,
|
|
|
|
|
|
gnomAD: rs587777526,
|
|
|
|
|
|
ClinVar: RCV000404317, RCV001265359, RCV004739651, RCV004975381
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>From a worldwide cohort of 78 patients with Helsmoortel-Van der Aa syndrome (HVDAS; 615873), Van Dijck et al. (2019) identified a c.2157C-A transversion in the ADNP gene, resulting in a tyr719-to-ter (Y719X) substitution, in 3 patients. A different mutation at the same nucleotide resulted in a Y719X substitution (611386.0005), indicating that this is a mutation hotspot. </p>
|
|
</span>
|
|
</div>
|
|
|
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|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 HELSMOORTEL-VAN DER AA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
ADNP, 4-BP DEL, 2496TAAA
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000128575, RCV000255626, RCV002312954
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>From a worldwide cohort of 78 patients with Helsmoortel-Van der Aa syndrome (HVDAS; 615873), Van Dijck et al. (2019) identified a 4-bp deletion in the ADNP gene (c.2496_2499delTAAA), resulting in a frameshift and premature termination (Asn832LysfsTer81), in 10 patients. The mutation had previously been identified in a patient by Helsmoortel et al. (2014). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
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<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 HELSMOORTEL-VAN DER AA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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ADNP, 1-BP DUP, 2156T
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ClinVar: RCV000170479, RCV000627402, RCV001249500, RCV002277322, RCV002426805
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<p>From a worldwide cohort of 78 patients with Helsmoortel-Van der Aa syndrome (HVDAS; 615873), Van Dijck et al. (2019) identified a 1-bp duplication (c.2156dupT) in the ADNP gene, resulting in a tyr719-to-ter (Y719X) substitution, in 8 patients. The authors identified 2 other mutations in the ADNP gene in patients with HVDAS that resulted in a Y719X substitution (see 611386.0005 and 611386.0009). This mutation had previously been identified in a patient by Helsmoortel et al. (2014). </p>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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<strong>Gene domain-specific DNA methylation episignatures highlight distinct molecular entities of ADNP syndrome.</strong>
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Clin. Epigenet. 11: 64, 2019. Note: Electronic Article.
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[PubMed: 31029150]
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Breen, M. S., Garg, P., Tang, L., Mendonca, D., Levy, T., Barbosa, M., Arnett, A. B., Kurtz-Nelson, E., Agolini, E., Battaglia, A., Chiocchetti, A. G., Freitag, C. M., and 17 others.
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Dresner, E., Agam, G., Gozes, I.
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<strong>Activity-dependent neuroprotective protein (ADNP) expression level is correlated with the expression of the sister protein ADNP2: deregulation in schizophrenia.</strong>
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<p class="mim-text-font">
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Gozes, I.
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<strong>Activity-dependent neuroprotective protein: from gene to drug candidate.</strong>
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Pharm. Ther. 114: 146-154, 2007.
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Helsmoortel, C., Vulto-van Silfhout, A. T., Coe, B. P., Vandeweyer, G., Rooms, L., van den Ende, J., Schuurs-Hoeijmakers, J. H. M., Marcelis, C. L., Willemsen, M. H., Vissers, L. E. L. M., Yntema, H. G., Bakshi, M., and 13 others.
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<strong>A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP.</strong>
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Nature Genet. 46: 380-384, 2014.
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[PubMed: 24531329]
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[Full Text: https://doi.org/10.1038/ng.2899]
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<p class="mim-text-font">
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Mandel, S., Gozes, I.
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<strong>Activity-dependent neuroprotective protein constitutes a novel element in the SWI/SNF chromatin remodeling complex.</strong>
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J. Biol. Chem. 282: 34448-34456, 2007.
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[PubMed: 17878164]
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[Full Text: https://doi.org/10.1074/jbc.M704756200]
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<p class="mim-text-font">
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Mandel, S., Rechavi, G., Gozes, I.
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<strong>Activity-dependent neuroprotective protein (ADNP) differentially interacts with chromatin to regulate genes essential for embryogenesis.</strong>
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Dev. Biol. 303: 814-824, 2007.
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[PubMed: 17222401]
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[Full Text: https://doi.org/10.1016/j.ydbio.2006.11.039]
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Nagase, T., Ishikawa, K., Suyama, M., Kikuno, R., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O.
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<strong>Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</strong>
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[PubMed: 9872452]
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[Full Text: https://doi.org/10.1093/dnares/5.5.277]
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</p>
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</li>
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<p class="mim-text-font">
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Ostapcuk, V., Mohn, F., Carl, S. H., Basters, A., Hess, D., Iesmantavicius, V., Lampersberger, L., Flemr, M., Pandey, A., Thoma, N. H., Betschinger, J., Buhler, M.
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<strong>Activity-dependent neuroprotective protein recruits HP1 and CHD4 to control lineage-specifying genes.</strong>
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Nature 557: 739-743, 2018.
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[PubMed: 29795351]
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[Full Text: https://doi.org/10.1038/s41586-018-0153-8]
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</p>
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</li>
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Pescosolido, M. F., Schwede, M., Johnson Harrison, A., Schmidt, M., Gamsiz, E. D., Chen, W. S., Donahue, J. P., Shur, N., Jerskey, B. A., Phornphutkul, C., Morrow, E. M.
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<strong>Expansion of the clinical phenotype associated with mutations in activity-dependent neuroprotective protein.</strong>
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J. Med. Genet. 51: 587-589, 2014.
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[PubMed: 25057125]
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[Full Text: https://doi.org/10.1136/jmedgenet-2014-102444]
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</p>
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</li>
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<p class="mim-text-font">
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Pinhasov, A., Mandel, S., Torchinsky, A., Giladi, E., Pittel, Z., Goldsweig, A. M., Servoss, S. J., Brenneman, D. E., Gozes, I.
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<strong>Activity-dependent neuroprotective protein: a novel gene essential for brain formation.</strong>
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Brain Res. Dev. Brain Res. 144: 83-90, 2003.
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[PubMed: 12888219]
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[Full Text: https://doi.org/10.1016/s0165-3806(03)00162-7]
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</p>
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<li>
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<p class="mim-text-font">
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Van Dijck, A., Vulto-van Silfhout, A. T., Cappuyns, E., van der Werf,, I M., Mancini, G. M., Tzschach, A., Bernier, R., Gozes, I., Eichler, E. E., Romano, C., Lindstrand, A., Nordgren, A., and 9 others.
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<strong>Clinical presentation of a complex neurodevelopmental disorder caused by mutations in ADNP.</strong>
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Biol. Psychiatry 85: 287-297, 2019.
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[PubMed: 29724491]
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[Full Text: https://doi.org/10.1016/j.biopsych.2018.02.1173]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Zamostiano, R., Pinhasov, A., Gelber, E., Steingart, R. A., Seroussi, E., Giladi, E., Bassan, M., Wollman, Y., Eyre, H. J., Mulley, J. C., Brenneman, D. E., Gozes, I.
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<strong>Cloning and characterization of the human activity-dependent neuroprotective protein.</strong>
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J. Biol. Chem. 276: 708-714, 2001.
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[PubMed: 11013255]
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[Full Text: https://doi.org/10.1074/jbc.M007416200]
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Hilary J. Vernon - updated : 02/24/2021<br>Carol A. Bocchini - updated : 02/12/2021<br>Ada Hamosh - updated : 08/20/2018<br>Patricia A. Hartz - updated : 03/31/2017<br>Ada Hamosh - updated : 05/11/2015<br>Cassandra L. Kniffin - updated : 5/4/2015<br>Cassandra L. Kniffin - updated : 7/9/2014
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