4428 lines
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Entry
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- *604095 - ECTODYSPLASIN A RECEPTOR; EDAR
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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">*604095</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="#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="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#evolution">Evolution</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/604095">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li 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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</ul>
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</nav>
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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=ENSG00000135960;t=ENST00000258443" 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=10913" 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=604095" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000135960;t=ENST00000258443" 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_022336,XM_006712204" 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_022336" 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=604095" 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=04974&isoform_id=04974_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/EDAR" 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/5737736,5737746,11641231,21263572,51476430,62739576,62739796,119574253,119574254,189054012,194384654,578803520,2133013437,2462569521" 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/Q9UNE0" 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=10913" 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=ENSG00000135960;t=ENST00000258443" 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=EDAR" 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=EDAR" 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+10913" 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/EDAR" 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:10913" 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/10913" 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=chr2&hgg_gene=ENST00000258443.7&hgg_start=108894471&hgg_end=108989220&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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=604095[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=604095[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/EDAR/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/ENSG00000135960" 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=EDAR" 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=EDAR" 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=EDAR" 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=EDAR&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/PA27602" 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:2895" 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:1343498" 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/EDAR#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:1343498" 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/10913/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/results?search_type=advanced&omia_id=001695,002128,002687,002697" class="mim-tip-hint" title="OMIA" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OMIA', 'domain': 'omia.angis.org.au'})">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=10913" 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-070117-2062" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:10913" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=EDAR&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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604095
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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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ECTODYSPLASIN A RECEPTOR; EDAR
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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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ECTODYSPLASIN 1, ANHIDROTIC RECEPTOR<br />
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DOWNLESS, MOUSE, HOMOLOG OF; DL<br />
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ECTODYSPLASIN A1 ISOFORM RECEPTOR<br />
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EDA-A1 RECEPTOR<br />
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EDA-A1R<br />
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EDA1R
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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=EDAR" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">EDAR</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/2/550?start=-3&limit=10&highlight=550">2q13</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:108894471-108989220&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'})">2:108,894,471-108,989,220</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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<span class="hidden-sm hidden-xs pull-right">
|
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<a href="/clinicalSynopsis/table?mimNumber=612630,129490,224900" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
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</a>
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</span>
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="3">
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<span class="mim-font">
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<a href="/geneMap/2/550?start=-3&limit=10&highlight=550">
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2q13
|
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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[Hair morphology 1, hair thickness]
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/612630"> 612630 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
|
|
Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, 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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<a href="/entry/129490"> 129490 </a>
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal 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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<tr>
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<td>
|
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<span class="mim-font">
|
|
Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/224900"> 224900 </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 recessive">AR</abbr>
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
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<p>Hypohidrotic ectodermal dysplasia (HED) results in abnormal morphogenesis of teeth, hair, and eccrine sweat glands. Autosomal recessive forms of the disorder exist at 2 separate loci ('crinkled,' cr, and 'downless,' dl) in mice. A candidate gene has been identified at the dl locus that is mutated in both dl and Dl(sleek) (Dl(slk)) mutant alleles. <a href="#9" class="mim-tip-reference" title="Monreal, A. W., Ferguson, B. M., Headon, D. J., Street, S. L., Overbeek, P. A., Zonana, J. <strong>Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia.</strong> Nature Genet. 22: 366-369, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10431241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10431241</a>] [<a href="https://doi.org/10.1038/11937" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10431241">Monreal et al. (1999)</a> isolated and characterized EDAR, the human Dl homolog. The putative protein is predicted to have a single transmembrane domain, and shows similarity to 2 separate domains of the tumor necrosis factor (TNF; <a href="/entry/191160">191160</a>) receptor (TNFR) family. The DL gene encodes a protein of 448 amino acids that is 91% identical to the mouse dl. The protein contains a single transmembrane domain with a type 1 membrane topology (extracellular amino terminus). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10431241" 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="#18" class="mim-tip-reference" title="Yan, M., Wang, L.-C., Hymowitz, S. G., Schilbach, S., Lee, J., Goddard, A., de Vos, A. M., Gao, W.-Q., Dixit, V. M. <strong>Two-amino acid molecular switch in an epithelial morphogen that regulates binding to two distinct receptors.</strong> Science 290: 523-527, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11039935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11039935</a>] [<a href="https://doi.org/10.1126/science.290.5491.523" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11039935">Yan et al. (2000)</a> found that EDAR binds only EDA-A1 (see EDA; <a href="/entry/300451">300451</a>), an ectodysplasin isoform that encodes a 391-amino acid protein with a domain similar to TNF at the C terminus. They examined the expression of EDAR in developing mouse skin by in situ hybridization. At embryonic day 14, EDAR transcripts were clearly present in the basal cells of the developing epidermis, with elevated focal expression in placodes. By embryonic days 16 and 17, EDAR was expressed in large amounts in the maturing follicles. By postnatal day 1, the pattern of expression was confined to the hair follicles. In addition, <a href="#18" class="mim-tip-reference" title="Yan, M., Wang, L.-C., Hymowitz, S. G., Schilbach, S., Lee, J., Goddard, A., de Vos, A. M., Gao, W.-Q., Dixit, V. M. <strong>Two-amino acid molecular switch in an epithelial morphogen that regulates binding to two distinct receptors.</strong> Science 290: 523-527, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11039935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11039935</a>] [<a href="https://doi.org/10.1126/science.290.5491.523" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11039935">Yan et al. (2000)</a> identified an X-linked ectodysplasin receptor, XEDAR (<a href="/entry/300276">300276</a>), that binds to the EDA-A2 isoform of EDA. EDA-A2 is identical to EDA-A1 except for a 2-residue deletion of glu308 and val309 that is caused by an internal splice donor site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11039935" 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="Doffinger, R., Smahi, A., Bessia, C., Geissmann, F., Feinberg, J., Durandy, A., Bodemer, C., Kenwrick, S., Dupuis-Girod, S., Blanche, S., Wood, P., Rabia, S. H., and 16 others. <strong>X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappa-B signaling.</strong> Nature Genet. 27: 277-285, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11242109/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11242109</a>] [<a href="https://doi.org/10.1038/85837" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11242109">Doffinger et al. (2001)</a> demonstrated that DL triggers NF-kappa-B (see <a href="/entry/164011">164011</a>) through the NEMO protein (<a href="/entry/300248">300248</a>), indicating that anhidrotic ectodermal dysplasia results from impaired NF-kappa-B signaling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11242109" 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="#3" class="mim-tip-reference" title="Elomaa, O., Pulkkinen, K., Hannelius, U., Mikkola, M., Saarialho-Kere, U., Kere, J. <strong>Ectodysplasin is released by proteolytic shedding and binds to the EDAR protein.</strong> Hum. Molec. Genet. 10: 953-962, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11309369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11309369</a>] [<a href="https://doi.org/10.1093/hmg/10.9.953" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11309369">Elomaa et al. (2001)</a> showed that ectodysplasin is released from cells to the culture medium, and that EDAR is able to coprecipitate EDA-A1, confirming that they form a ligand-receptor pair. In situ hybridization and immunostaining demonstrated that ectodysplasin and EDAR are expressed in adjacent or partially overlapping layers in the developing human skin. The authors concluded that as a soluble ligand ectodysplasin is able to interact with EDAR and mediate signals needed for the development of ectodermal appendages. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11309369" 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="#16" class="mim-tip-reference" title="Trompouki, E., Hatzivassiliou, E., Tsichritzis, T., Farmer, H., Ashworth, A., Mosialos, G. <strong>CYLD is a deubiquitinating enzyme that negatively regulates NF-kappa-B activation by TNFR family members.</strong> Nature 424: 793-796, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12917689/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12917689</a>] [<a href="https://doi.org/10.1038/nature01803" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12917689">Trompouki et al. (2003)</a> identified CYLD (<a href="/entry/605018">605018</a>) as a deubiquitinating enzyme that negatively regulates activation of NF-kappa-B by specific TNFRs. Loss of the deubiquitinating activity of CYLD correlated with tumorigenesis. CYLD inhibits activation of NF-kappa-B by the TNFR family members CD40 (<a href="/entry/109535">109535</a>), XEDAR, and EDAR in a manner that depends on deubiquitinating activity of CYLD. Downregulation of CYLD by RNA-mediated interference augments both basal and CD40-mediated activation of NF-kappa-B. The inhibition of NF-kappa-B activation by CYLD is mediated, at least in part, by the deubiquitination and inactivation of TNFR-associated factor 2 (TRAF2; <a href="/entry/601895">601895</a>) and, to a lesser extent, TRAF6 (<a href="/entry/602355">602355</a>). <a href="#16" class="mim-tip-reference" title="Trompouki, E., Hatzivassiliou, E., Tsichritzis, T., Farmer, H., Ashworth, A., Mosialos, G. <strong>CYLD is a deubiquitinating enzyme that negatively regulates NF-kappa-B activation by TNFR family members.</strong> Nature 424: 793-796, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12917689/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12917689</a>] [<a href="https://doi.org/10.1038/nature01803" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12917689">Trompouki et al. (2003)</a> concluded that CYLD is a negative regulator of the cytokine-mediated activation of NF-kappa-B that is required for appropriate cellular homeostasis of skin appendages. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12917689" 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 transfected human embryonic kidney cells and fibroblasts from mouse embryos defective in NF-kappa-B pathway components, <a href="#15" class="mim-tip-reference" title="Shindo, M., Chaudhary, P. M. <strong>The ectodermal dysplasia receptor represses the Lef-1/beta-catenin-dependent transcription independent of NF-kappa-B activation.</strong> Biochem. Biophys. Res. Commun. 315: 73-78, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15013427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15013427</a>] [<a href="https://doi.org/10.1016/j.bbrc.2004.01.025" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15013427">Shindo and Chaudhary (2004)</a> showed that EDAR signaling repressed LEF1 (<a href="/entry/153245">153245</a>)-beta-catenin (CTNNB1; <a href="/entry/116806">116806</a>)-dependent transcription independent of its stimulatory effect on NF-kappa-B activity. Human EDAR with the arg420-to-gln (R420Q; <a href="#0006">604095.0006</a>) mutation associated with anhidrotic ectodermal dysplasia exhibited defects in both NF-kappa-B activation and LEF1/beta-catenin repression. In contrast, mouse Edar with a mutation associated with the downless phenotype retained significant ability to activate NF-kappa-B signaling and repress Lef1/beta-catenin activity. <a href="#15" class="mim-tip-reference" title="Shindo, M., Chaudhary, P. M. <strong>The ectodermal dysplasia receptor represses the Lef-1/beta-catenin-dependent transcription independent of NF-kappa-B activation.</strong> Biochem. Biophys. Res. Commun. 315: 73-78, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15013427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15013427</a>] [<a href="https://doi.org/10.1016/j.bbrc.2004.01.025" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15013427">Shindo and Chaudhary (2004)</a> concluded that, by stimulating NF-kappa-B activity and repressing LEF1/beta-catenin-dependent transcription, EDAR has opposing effects on 2 major and independent pathways involved in ectodermal differentiation and hair follicle morphogenesis. Since LEF1/beta-catenin controls expression of EDA, the results suggested negative feedback regulation of the EDA-EDAR axis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15013427" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#9" class="mim-tip-reference" title="Monreal, A. W., Ferguson, B. M., Headon, D. J., Street, S. L., Overbeek, P. A., Zonana, J. <strong>Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia.</strong> Nature Genet. 22: 366-369, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10431241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10431241</a>] [<a href="https://doi.org/10.1038/11937" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10431241">Monreal et al. (1999)</a> localized the EDAR gene to a position 10.1 cR from marker AFMA037YB9 between markers D2S293 and D2S121, an interval contained in chromosome 2q11-q13. Autosomal recessive hypohidrotic ectodermal dysplasia (HED; <a href="/entry/224900">224900</a>) does not map to the candidate gene locus in all families, implying the existence of at least 1 additional human locus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10431241" 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="#13" class="mim-tip-reference" title="Sabeti, P. C., Varilly, P., Fry, B., Lohmueller, J., Hostetter, E., Cotsapas, C., Xie, X., Byrne, E. H., McCarroll, S. A., Gaudet, R., Schaffner, S. F., Lander, E. S., International HapMap Consortium. <strong>Genome-wide detection and characterization of positive selection in human populations.</strong> Nature 449: 913-918, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17943131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17943131</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17943131[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/nature06250" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17943131">Sabeti et al. (2007)</a> reported an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2. The analysis revealed more than 300 strong candidate regions that appeared to have undergone recent natural selection. Examination of 22 of the strongest regions highlighted 3 cases in which 2 genes in a common biologic process had apparently undergone positive selection in the same population: LARGE (<a href="/entry/603590">603590</a>) and DMD (<a href="/entry/300377">300377</a>), both related to infection by the Lassa virus, in West Africa; SLC24A5 (<a href="/entry/609802">609802</a>) and SLC45A2 (<a href="/entry/606202">606202</a>), both involved in skin pigmentation, in Europe; and EDAR and EDA2R (<a href="/entry/300276">300276</a>), both involved in the development of hair follicles, in Asia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17943131" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#9" class="mim-tip-reference" title="Monreal, A. W., Ferguson, B. M., Headon, D. J., Street, S. L., Overbeek, P. A., Zonana, J. <strong>Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia.</strong> Nature Genet. 22: 366-369, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10431241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10431241</a>] [<a href="https://doi.org/10.1038/11937" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10431241">Monreal et al. (1999)</a> identified mutations in the DL gene in 3 families displaying recessive inheritance of HED (ECTD10B; <a href="/entry/224900">224900</a>) and 2 with dominant inheritance (ECTD10A; <a href="/entry/129490">129490</a>). They identified 7 variants, 2 of which were detected in the control population. A single change involving a basepair transition in exon 12 (arg358 to ter, <a href="#0005">604095.0005</a>; arg420 to gln, <a href="#0006">604095.0006</a>) was found in each dominant family. The arg358-to-ter mutation resulted in a truncation of the predicted cytoplasmic portion of the protein, similar to the effect of the dominant mutation Dl(slk) in the mouse, which truncates the protein before the possible death domain. It had been shown that coexpression of a truncated TNFR with a wildtype receptor results in a dominant-negative effect on function, presumably due to lack of homotrimerization of the death domains. Dominant-negative mutations have also been described in the FAS antigen (<a href="/entry/134637">134637</a>), a member of the TNFR family, in patients with autoimmune lymphoproliferative syndrome (<a href="/entry/601859">601859</a>). The nonconserved missense mutation arg420 to gln in a second family was also in the predicted cytoplasmic portion of the protein within the potential death domain. <a href="#9" class="mim-tip-reference" title="Monreal, A. W., Ferguson, B. M., Headon, D. J., Street, S. L., Overbeek, P. A., Zonana, J. <strong>Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia.</strong> Nature Genet. 22: 366-369, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10431241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10431241</a>] [<a href="https://doi.org/10.1038/11937" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10431241">Monreal et al. (1999)</a> showed that DL mutations produce recessive loss-of-function, as well as likely dominant-negative, effects. One hypothesis is that the protein functions as a multimeric receptor and is related to the TNFR family. The authors noted that ectodysplasin-A, the protein abnormal in X-linked hypohidrotic ectodermal dysplasia, shows a highly significant match in its extracellular domain with the TNF family profile. Further study will be required to test if DL and ectodysplasin-A proteins function as receptor and ligand in a common signaling pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10431241" 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>To assess the role of the EDAR gene in HED, <a href="#1" class="mim-tip-reference" title="Chassaing, N., Bourthoumieu, S., Cossee, M., Calvas, P., Vincent, M.-C. <strong>Mutations in EDAR account for one-quarter of non-ED1-related hypohidrotic ectodermal dysplasia.</strong> Hum. Mutat. 27: 255-259, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16435307/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16435307</a>] [<a href="https://doi.org/10.1002/humu.20295" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16435307">Chassaing et al. (2006)</a> screened for mutations in 37 unrelated HED families or sporadic cases with no detected mutations in the EDA gene (<a href="/entry/300451">300451</a>). They identified 11 different mutations, 9 of which were novel variants, in 2 familial and 7 sporadic cases. Seven of the 11 were recessive and the other 4 were considered to be probably dominant. The study demonstrated that EDAR is implicated in about 25% of non-EDA HED. They diagrammed the process by which, during hair follicle morphogenesis, EDAR is activated by the product of the EDA gene and uses EDARADD (<a href="/entry/606603">606603</a>) as an adaptor to activate the NF-kappa-B (see <a href="/entry/164011">164011</a>) signaling pathway (<a href="#8" class="mim-tip-reference" title="Mikkola, M. L., Thesleff, I. <strong>Ectodysplasin signaling in development.</strong> Cytokine Growth Factor Rev. 14: 211-224, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12787560/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12787560</a>] [<a href="https://doi.org/10.1016/s1359-6101(03)00020-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12787560">Mikkola and Thesleff, 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16435307+12787560" 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 an 18-year-old Lebanese woman with a severe form of autosomal recessive anhidrotic ectodermal dysplasia with unusual clinical features including absence of breasts, extranumerary areola and nipple on the left side, and marked palmoplantar hyperkeratosis, <a href="#7" class="mim-tip-reference" title="Megarbane, H., Cluzeau, C., Bodemer, C., Fraitag, S., Chababi-Atallah, M., Megarbane, A., Smahi, A. <strong>Unusual presentation of a severe autosomal recessive anhydrotic (sic) ectodermal dysplasia with a novel mutation in the EDAR gene.</strong> Am. J. Med. Genet. 146A: 2657-2662, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18816645/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18816645</a>] [<a href="https://doi.org/10.1002/ajmg.a.32509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18816645">Megarbane et al. (2008)</a> identified a novel homozygous splice site mutation in the EDAR gene (IVS9+G-A; <a href="#0013">604095.0013</a>). RT-PCR analysis performed on whole skin biopsies and genes known to be expressed in skin appendages indicated that the mutation severely impairs EDAR cDNA splicing, resulting in total absence of EDAR transcripts and consequently of the EDAR protein. <a href="#7" class="mim-tip-reference" title="Megarbane, H., Cluzeau, C., Bodemer, C., Fraitag, S., Chababi-Atallah, M., Megarbane, A., Smahi, A. <strong>Unusual presentation of a severe autosomal recessive anhydrotic (sic) ectodermal dysplasia with a novel mutation in the EDAR gene.</strong> Am. J. Med. Genet. 146A: 2657-2662, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18816645/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18816645</a>] [<a href="https://doi.org/10.1002/ajmg.a.32509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18816645">Megarbane et al. (2008)</a> hypothesized that the mutation leads to the loss of EDAR/NF-kappa-B signaling. They speculated that the mutation impairs Wnt (see <a href="/entry/164820">164820</a>)/B-catenin (<a href="/entry/116806">116806</a>) downregulation, which may modify the balance between signals necessary to mammary gland development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18816645" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Fujimoto, A., Kimura, R., Ohashi, J., Omi, K., Yuliwulandari, R., Batubara, L., Mustofa, M. S., Samakkarn, U., Settheetham-Ishida, W., Ishida, T., Morishita, Y., Furusawa, T., Nakazawa, M., Ohtsuka, R., Tokunaga, K. <strong>A scan for genetic determinants of human hair morphology: EDAR is associated with Asian hair thickness.</strong> Hum. Molec. Genet. 17: 835-843, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18065779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18065779</a>] [<a href="https://doi.org/10.1093/hmg/ddm355" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18065779">Fujimoto et al. (2008)</a> identified a mutation in the EDAR gene associated with variation in hair thickness (<a href="#0011">604095.0011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18065779" 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="#6" class="mim-tip-reference" title="Headon, D. J., Overbeek, P. A. <strong>Involvement of a novel Tnf receptor homologue in hair follicle induction.</strong> Nature Genet. 22: 370-374, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10431242/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10431242</a>] [<a href="https://doi.org/10.1038/11943" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10431242">Headon and Overbeek (1999)</a> used positional cloning to identify the mouse dl gene, which encodes a novel member of the tumor necrosis factor receptor family. The mutant phenotype and dl expression pattern suggested that this gene encodes a receptor that specifies hair follicle fate. Its ligand is likely to be the product of the 'Tabby' gene, as Ta mutants have a phenotype identical to that of dl mutants and Ta encodes a tumor necrosis factor receptor-like protein. Northern blot analysis of mRNA from embryonic day 17.5 skin revealed a 3.8-kb transcript in all genotypes except Dl(slk) and dl(OVE1B). At embryonic day 13, before hair follicle induction, dl is expressed throughout the basal layer of the epidermis. By embryonic day 15, expression has become upregulated in foci of induced cells initiating and undergoing follicular morphogenesis and is beginning to be downregulated in surrounding cells. By embryonic day 17, dl is expressed in secondary follicles and elongating primary follicles, but is no longer detected in the interfollicular epidermis. There was an absence of expression of early hair follicle markers, including Bmp4 and Shh, in dl mutant skin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10431242" 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 examining embryonic mouse skin cultures, <a href="#10" class="mim-tip-reference" title="Mou, C., Jackson, B., Schneider, P., Overbeek, P. A., Headon, D. J. <strong>Generation of the primary hair follicle pattern.</strong> Proc. Nat. Acad. Sci. 103: 9075-9080, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16769906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16769906</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16769906[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0600825103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16769906">Mou et al. (2006)</a> determined that Edar is central to the generation of the primary hair follicle pattern. They found a rapid Edar-positive feedback mechanism in the epidermis coupled with induction of dermal Bmp4 (<a href="/entry/112262">112262</a>) and Bmp7 (<a href="/entry/112267">112267</a>), which repressed epidermal Edar expression and follicle fate in cells neighboring nascent follicles. Edar activation also induced connective tissue growth factor (CTGF; <a href="/entry/121009">121009</a>), an inhibitor of BMP signaling, allowing BMP action only at a distance from nascent follicles. Consistent with this mode, transgenic hyperactivation of Edar signaling led to widespread overproduction of hair follicles. Edar-mediated stabilization of beta-catenin (see CTNNB1, <a href="/entry/116806">116806</a>)-active foci appeared to be a key event in determining follicle location. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16769906" 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="#11" class="mim-tip-reference" title="Mou, C., Thomason, H. A., Willan, P. M., Clowes, C., Harris, W. E., Drew, C. F., Dixon, J., Dixon, M. J., Headon, D. J. <strong>Enhanced ectodysplasin-A receptor (EDAR) signaling alters multiple fiber characteristics to produce the East Asian hair form.</strong> Hum. Mutat. 29: 1405-1411, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18561327/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18561327</a>] [<a href="https://doi.org/10.1002/humu.20795" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18561327">Mou et al. (2008)</a> found that mice with overexpression of the Edar gene displayed a coarser coat hair phenotype compared to wildtype mice. The diameter of each hair type was increased by 10 to 25% upon elevation of Edar signaling, corresponding to an increase of cross-sectional area of 21 to 56%. In addition, the hair of transgenic mice showed increased straightness and a more circular cross-section appearance. Primary hair follicles of the transgenic mice showed an enlarged bulb region with Edar expression within the bulb, and transgenic mouse embryos showed larger hair follicle placodes, which represent the organ primordia. <a href="#11" class="mim-tip-reference" title="Mou, C., Thomason, H. A., Willan, P. M., Clowes, C., Harris, W. E., Drew, C. F., Dixon, J., Dixon, M. J., Headon, D. J. <strong>Enhanced ectodysplasin-A receptor (EDAR) signaling alters multiple fiber characteristics to produce the East Asian hair form.</strong> Hum. Mutat. 29: 1405-1411, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18561327/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18561327</a>] [<a href="https://doi.org/10.1002/humu.20795" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18561327">Mou et al. (2008)</a> commented that the phenotype was similar to that observed in East Asian human hair, which is thicker and more circular on cross-section profile and is associated with a SNP in the EDAR gene (<a href="#0011">604095.0011</a>) that causes increased downstream NFKB activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18561327" 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 consanguineous family with autosomal recessive hypohidrotic ectodermal dysplasia (ECTD10B; <a href="/entry/224900">224900</a>), <a href="#9" class="mim-tip-reference" title="Monreal, A. W., Ferguson, B. M., Headon, D. J., Street, S. L., Overbeek, P. A., Zonana, J. <strong>Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia.</strong> Nature Genet. 22: 366-369, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10431241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10431241</a>] [<a href="https://doi.org/10.1038/11937" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10431241">Monreal et al. (1999)</a> identified an 18-bp deletion at the 3-prime end of intron 2 of the EDAR gene. The deletion altered 7 of 10 basepairs constituting a polypyrimidine stretch at the acceptor splice site, reducing the number of pyrimidines from 8 to 3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10431241" 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> rs121908450 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908450;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/rs121908450?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=rs121908450" 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=rs121908450" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 affected sibs from a nonconsanguineous family with autosomal recessive hypohidrotic ectodermal dysplasia (ECTD10B; <a href="/entry/224900">224900</a>), <a href="#9" class="mim-tip-reference" title="Monreal, A. W., Ferguson, B. M., Headon, D. J., Street, S. L., Overbeek, P. A., Zonana, J. <strong>Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia.</strong> Nature Genet. 22: 366-369, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10431241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10431241</a>] [<a href="https://doi.org/10.1038/11937" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10431241">Monreal et al. (1999)</a> detected a G-to-A transition at nucleotide 266 of the EDAR gene resulting in a nonconservative change of arg89 to his in the extracellular domain. The affected children were heterozygous at flanking polymorphic loci, but failed to inherit a paternal allele at the D2S1893 locus. Sequencing revealed their mother to be heterozygous for the variant, whereas their father was hemizygous wildtype. Thus, the affected individuals were compound heterozygotes, with their paternal allele containing a large deletion of indeterminate size (see <a href="#0003">604095.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10431241" 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="#17" class="mim-tip-reference" title="Van der Hout, A. H., Oudesluijs, G. G., Venema, A., Verheij, J. B. G. M., Mol, B. G. J., Rump, P., Brunner, H. G., Vos, Y. J., van Essen, A. J. <strong>Mutation screening of the ectodysplasin-A receptor gene EDAR in hypohidrotic ectodermal dysplasia.</strong> Europ. J. Hum. Genet. 16: 673-679, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18231121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18231121</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5202012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18231121">Van der Hout et al. (2008)</a> reported 2 brothers with hypohidrotic ectodermal dysplasia resulting from compound heterozygosity for the R89H and D110A (<a href="#0009">604095.0009</a>) mutations in the EDAR gene. The unaffected father carried the D110A mutation. However, the mother, who was heterozygous for the R89H mutation, was mildly affected with hypohidrosis and few permanent teeth, consistent with autosomal dominant hypohidrotic ectodermal dysplasia (ECTD10A; <a href="/entry/129490">129490</a>). <a href="#17" class="mim-tip-reference" title="Van der Hout, A. H., Oudesluijs, G. G., Venema, A., Verheij, J. B. G. M., Mol, B. G. J., Rump, P., Brunner, H. G., Vos, Y. J., van Essen, A. J. <strong>Mutation screening of the ectodysplasin-A receptor gene EDAR in hypohidrotic ectodermal dysplasia.</strong> Europ. J. Hum. Genet. 16: 673-679, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18231121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18231121</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5202012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18231121">Van der Hout et al. (2008)</a> concluded that some presumably 'recessive' mutations may show phenotypic expression in carriers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18231121" 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>For discussion of the large deletion of indeterminate size that was found in the EDAR gene in compound heterozygous state in 2 sibs with autosomal recessive hypohidrotic ectodermal dysplasia (ECTD10B; <a href="/entry/224900">224900</a>) by <a href="#9" class="mim-tip-reference" title="Monreal, A. W., Ferguson, B. M., Headon, D. J., Street, S. L., Overbeek, P. A., Zonana, J. <strong>Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia.</strong> Nature Genet. 22: 366-369, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10431241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10431241</a>] [<a href="https://doi.org/10.1038/11937" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10431241">Monreal et al. (1999)</a>, see <a href="#0002">604095.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10431241" 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> rs121908451 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908451;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/rs121908451?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=rs121908451" 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=rs121908451" 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=RCV000006209 OR RCV003764531" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006209, RCV003764531" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006209...</a>
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<p>In a family with autosomal recessive hypohidrotic ectodermal dysplasia (ECTD10B; <a href="/entry/224900">224900</a>), <a href="#9" class="mim-tip-reference" title="Monreal, A. W., Ferguson, B. M., Headon, D. J., Street, S. L., Overbeek, P. A., Zonana, J. <strong>Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia.</strong> Nature Genet. 22: 366-369, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10431241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10431241</a>] [<a href="https://doi.org/10.1038/11937" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10431241">Monreal et al. (1999)</a> identified a homozygous T-to-C transition at nucleotide 259 of the EDAR gene resulting in a cys-to-arg substitution at codon 87 (C87R) in affected individuals. The mutation resulted in a nonconservative change in the extracellular domain, possibly affecting intra- or interchain disulfide bond formation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10431241" 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 ECTODERMAL DYSPLASIA 10A, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL DOMINANT</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">rs121908452 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908452;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=rs121908452" 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=rs121908452" 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=RCV000006210 OR RCV000255664 OR RCV000532015 OR RCV001261883 OR RCV003505080" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006210, RCV000255664, RCV000532015, RCV001261883, RCV003505080" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006210...</a>
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<p>In a family with autosomal dominant hypohidrotic ectodermal dysplasia (ECTD10A; <a href="/entry/129490">129490</a>), <a href="#9" class="mim-tip-reference" title="Monreal, A. W., Ferguson, B. M., Headon, D. J., Street, S. L., Overbeek, P. A., Zonana, J. <strong>Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia.</strong> Nature Genet. 22: 366-369, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10431241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10431241</a>] [<a href="https://doi.org/10.1038/11937" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10431241">Monreal et al. (1999)</a> identified a C-to-T transition at nucleotide 1072 in exon 12 of the EDAR gene resulting in an arg-to-ter substitution at codon 358 (R358X). This mutation was found in heterozygosity in all affected individuals. The mutation resulted in a truncation of the predicted cytoplasmic portion of the protein, similar to the effect of the dominant mutation Dl(slk) in the mouse, which truncates the protein before the possible death domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10431241" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 ECTODERMAL DYSPLASIA 10A, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL DOMINANT</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">rs121908453 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908453;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=rs121908453" 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=rs121908453" 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=RCV000006211 OR RCV000255701 OR RCV000755721 OR RCV001050412 OR RCV001334149" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006211, RCV000255701, RCV000755721, RCV001050412, RCV001334149" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006211...</a>
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<p>In all affected members of a family with autosomal dominant hypohidrotic ectodermal dysplasia (ECTD10A; <a href="/entry/129490">129490</a>), <a href="#9" class="mim-tip-reference" title="Monreal, A. W., Ferguson, B. M., Headon, D. J., Street, S. L., Overbeek, P. A., Zonana, J. <strong>Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia.</strong> Nature Genet. 22: 366-369, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10431241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10431241</a>] [<a href="https://doi.org/10.1038/11937" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10431241">Monreal et al. (1999)</a> identified a G-to-A transition at nucleotide 1259 in exon 12 of the EDAR gene that resulted in an arg-to-gln substitution at codon 420 (R420Q). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10431241" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 ECTODERMAL DYSPLASIA 10B, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL RECESSIVE</strong>
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<p>In a Japanese woman with autosomal recessive hypohidrotic ectodermal dysplasia (ECTD10B; <a href="/entry/224900">224900</a>), <a href="#14" class="mim-tip-reference" title="Shimomura, Y., Sato, N., Miyashita, A., Hashimoto, T., Ito, M., Kuwano, R. <strong>A rare case of hypohidrotic ectodermal dysplasia caused by compound heterozygous mutations in the EDAR gene.</strong> J. Invest. Derm. 123: 649-655, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15373768/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15373768</a>] [<a href="https://doi.org/10.1111/j.0022-202X.2004.23405.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15373768">Shimomura et al. (2004)</a> identified compound heterozygosity for 2 mutations in the EDAR gene: a G-to-A transition in intron 2, resulting in an unstable transcript lacking exon 2, and a 1124G-A transition in exon 12, resulting in an arg375-to-his (R375H; <a href="#0008">604095.0008</a>) substitution within the intracellular DD domain. The patient's unaffected father carried the R375H mutation. In vitro functional expression studies showed that the R375H mutant protein did not interact with EDARADD (<a href="/entry/606603">606603</a>) and was functionally inactive. The patient had heat intolerance, sparse hair, periorbital wrinkling, and oligodontia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15373768" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 ECTODERMAL DYSPLASIA 10B, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL RECESSIVE</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> rs121908454 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908454;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/rs121908454?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=rs121908454" 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=rs121908454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the arg357-to-his (R357H) mutation in the EDAR gene that was found in compound heterozygous state in a patient with autosomal recessive hypohidrotic ectodermal dysplasia (ECTD10B; <a href="/entry/224900">224900</a>) by <a href="#14" class="mim-tip-reference" title="Shimomura, Y., Sato, N., Miyashita, A., Hashimoto, T., Ito, M., Kuwano, R. <strong>A rare case of hypohidrotic ectodermal dysplasia caused by compound heterozygous mutations in the EDAR gene.</strong> J. Invest. Derm. 123: 649-655, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15373768/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15373768</a>] [<a href="https://doi.org/10.1111/j.0022-202X.2004.23405.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15373768">Shimomura et al. (2004)</a>, see <a href="#0007">604095.0007</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15373768" 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>.0009 ECTODERMAL DYSPLASIA 10B, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL RECESSIVE</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> rs121908455 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908455;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/rs121908455?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=rs121908455" 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=rs121908455" 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=RCV000006214" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006214" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006214</a>
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<p>In 2 brothers with autosomal recessive hypohidrotic ectodermal dysplasia (ECTD10B; <a href="/entry/224900">224900</a>), <a href="#17" class="mim-tip-reference" title="Van der Hout, A. H., Oudesluijs, G. G., Venema, A., Verheij, J. B. G. M., Mol, B. G. J., Rump, P., Brunner, H. G., Vos, Y. J., van Essen, A. J. <strong>Mutation screening of the ectodysplasin-A receptor gene EDAR in hypohidrotic ectodermal dysplasia.</strong> Europ. J. Hum. Genet. 16: 673-679, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18231121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18231121</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5202012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18231121">van der Hout et al. (2008)</a> identified compound heterozygosity for 2 mutations in the EDAR gene: a 329A-C transversion in exon 4 resulting in an asp110-to-ala (D110A) substitution and the R89H (<a href="#0002">604095.0002</a>) mutation. The unaffected father was heterozygous for the D110A mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18231121" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0010 ECTODERMAL DYSPLASIA 10A, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL DOMINANT</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">rs121908456 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908456;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=rs121908456" 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=rs121908456" 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=RCV000006215" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006215" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006215</a>
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<p>In a woman with autosomal dominant hypohidrotic ectodermal dysplasia (ECTD10A; <a href="/entry/129490">129490</a>), <a href="#17" class="mim-tip-reference" title="Van der Hout, A. H., Oudesluijs, G. G., Venema, A., Verheij, J. B. G. M., Mol, B. G. J., Rump, P., Brunner, H. G., Vos, Y. J., van Essen, A. J. <strong>Mutation screening of the ectodysplasin-A receptor gene EDAR in hypohidrotic ectodermal dysplasia.</strong> Europ. J. Hum. Genet. 16: 673-679, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18231121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18231121</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5202012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18231121">van der Hout et al. (2008)</a> identified a heterozygous 1060G-T transversion in exon 12 of the EDAR gene, resulting in a glu354-to-ter (E354X) substitution. Her son was also affected but was not tested for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18231121" 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 HAIR MORPHOLOGY 1, HAIR THICKNESS</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> rs3827760 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs3827760;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/rs3827760?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=rs3827760" 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=rs3827760" 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=RCV000006216 OR RCV000174399 OR RCV000382959 OR RCV001133945 OR RCV001261884 OR RCV001523395 OR RCV001659684 OR RCV001659685 OR RCV001723544" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006216, RCV000174399, RCV000382959, RCV001133945, RCV001261884, RCV001523395, RCV001659684, RCV001659685, RCV001723544" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006216...</a>
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<p><a href="#4" class="mim-tip-reference" title="Fujimoto, A., Kimura, R., Ohashi, J., Omi, K., Yuliwulandari, R., Batubara, L., Mustofa, M. S., Samakkarn, U., Settheetham-Ishida, W., Ishida, T., Morishita, Y., Furusawa, T., Nakazawa, M., Ohtsuka, R., Tokunaga, K. <strong>A scan for genetic determinants of human hair morphology: EDAR is associated with Asian hair thickness.</strong> Hum. Molec. Genet. 17: 835-843, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18065779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18065779</a>] [<a href="https://doi.org/10.1093/hmg/ddm355" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18065779">Fujimoto et al. (2008)</a> identified a 1540T-C SNP (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs3827760;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs3827760</a>) in exon 12 of the EDAR gene, resulting in a val370-to-ala (V370A) substitution in the intracellular death domain. The C allele was present at a frequency of 87.6% in 180 Chinese and Japanese samples, compared to 0% in 120 European and African samples. A further study of 121 unrelated Indonesian individuals from the Java Island and 65 unrelated individuals of the Thai-Mai in Thailand showed a significant association of the 1540T/C SNP with cross-sectional area of hairs (<a href="/entry/612630">612630</a>) (p = 5.5 x 10(-3) and p = 9.5 x 10(-4), for the populations, respectively). In vitro functional expression studies showed that the C allele of this SNP in EDAR resulted in decreased downstream activity of NFKB (see <a href="/entry/164011">164011</a>) 48 hours after transfection into HeLa cells. By studying the geographic distribution of the 1540T/C SNP in the EDAR gene and using haplotype analysis, <a href="#4" class="mim-tip-reference" title="Fujimoto, A., Kimura, R., Ohashi, J., Omi, K., Yuliwulandari, R., Batubara, L., Mustofa, M. S., Samakkarn, U., Settheetham-Ishida, W., Ishida, T., Morishita, Y., Furusawa, T., Nakazawa, M., Ohtsuka, R., Tokunaga, K. <strong>A scan for genetic determinants of human hair morphology: EDAR is associated with Asian hair thickness.</strong> Hum. Molec. Genet. 17: 835-843, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18065779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18065779</a>] [<a href="https://doi.org/10.1093/hmg/ddm355" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18065779">Fujimoto et al. (2008)</a> concluded that the 1540C allele arose after the divergence of Asians from Europeans, and that its frequency has rapidly increased in East Asian populations due to positive selection. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18065779" 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 follow-up study, <a href="#5" class="mim-tip-reference" title="Fujimoto, A., Ohashi, J., Nishida, N., Miyagawa, T., Morishita, Y., Tsunoda, T., Kimura, R., Tokunaga, K. <strong>A replication study confirmed the EDAR gene to be a major contributor to population differentiation regarding head hair thickness in Asia.</strong> Hum. Genet. 124: 179-185, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18704500/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18704500</a>] [<a href="https://doi.org/10.1007/s00439-008-0537-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18704500">Fujimoto et al. (2008)</a> found a significant association between 1540C and increased hair cross-sectional area in a cohort of 189 Japanese individuals (p = 2.7 x 10(-6)). A stronger association was noted (p = 3.8 x 10(-10)) when the findings were combined with population results of the Thai-Mai and Indonesian cohorts from the previous study. The findings confirmed that EDAR is the genetic determinant of hair thickness, as well as a strong contributor to hair fiber thickness variation, in East Asian populations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18704500" 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 contrast to the findings of <a href="#4" class="mim-tip-reference" title="Fujimoto, A., Kimura, R., Ohashi, J., Omi, K., Yuliwulandari, R., Batubara, L., Mustofa, M. S., Samakkarn, U., Settheetham-Ishida, W., Ishida, T., Morishita, Y., Furusawa, T., Nakazawa, M., Ohtsuka, R., Tokunaga, K. <strong>A scan for genetic determinants of human hair morphology: EDAR is associated with Asian hair thickness.</strong> Hum. Molec. Genet. 17: 835-843, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18065779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18065779</a>] [<a href="https://doi.org/10.1093/hmg/ddm355" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18065779">Fujimoto et al. (2008)</a>, <a href="#11" class="mim-tip-reference" title="Mou, C., Thomason, H. A., Willan, P. M., Clowes, C., Harris, W. E., Drew, C. F., Dixon, J., Dixon, M. J., Headon, D. J. <strong>Enhanced ectodysplasin-A receptor (EDAR) signaling alters multiple fiber characteristics to produce the East Asian hair form.</strong> Hum. Mutat. 29: 1405-1411, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18561327/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18561327</a>] [<a href="https://doi.org/10.1002/humu.20795" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18561327">Mou et al. (2008)</a> found that the C allele (ala370) resulted in increased downstream activity of NFKB in transfected human cells after 18 hours. <a href="#11" class="mim-tip-reference" title="Mou, C., Thomason, H. A., Willan, P. M., Clowes, C., Harris, W. E., Drew, C. F., Dixon, J., Dixon, M. J., Headon, D. J. <strong>Enhanced ectodysplasin-A receptor (EDAR) signaling alters multiple fiber characteristics to produce the East Asian hair form.</strong> Hum. Mutat. 29: 1405-1411, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18561327/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18561327</a>] [<a href="https://doi.org/10.1002/humu.20795" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18561327">Mou et al. (2008)</a> stated that their results more accurately reflected physiologic conditions. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18561327+18065779" 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>For discussion of a possible association between the T1540C polymorphism and shovel-shaped incisors, see <a href="/entry/147400">147400</a>.</p>
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<strong>.0012 ECTODERMAL DYSPLASIA 10B, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL RECESSIVE</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">rs797044436 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs797044436;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=rs797044436" 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=rs797044436" 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=RCV000006217" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006217" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006217</a>
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<p>In affected members of a consanguineous Pakistani family with autosomal recessive hypohidrotic ectodermal dysplasia (ECTD10B; <a href="/entry/224900">224900</a>), <a href="#12" class="mim-tip-reference" title="Naeem, M., Muhammad, D., Ahmad, W. <strong>Novel mutations in the EDAR gene in two Pakistani consanguineous families with autosomal recessive hypohidrotic ectodermal dysplasia.</strong> Brit. J. Derm. 153: 46-50, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16029325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16029325</a>] [<a href="https://doi.org/10.1111/j.1365-2133.2005.06642.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16029325">Naeem et al. (2005)</a> identified a homozygous 4-bp deletion (718delAAAG) in exon 8 of the EDAR gene, resulting in a frameshift and premature termination. Affected individuals had classic features of the disorder, including sparse hair, absent eyebrows and eyelashes, missing teeth, decreased sweating, dry thin skin, periorbital wrinkling and hyperpigmentation, prominent lips, and a saddle-shaped nose. Heterozygous gene carriers were not affected. <a href="#12" class="mim-tip-reference" title="Naeem, M., Muhammad, D., Ahmad, W. <strong>Novel mutations in the EDAR gene in two Pakistani consanguineous families with autosomal recessive hypohidrotic ectodermal dysplasia.</strong> Brit. J. Derm. 153: 46-50, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16029325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16029325</a>] [<a href="https://doi.org/10.1111/j.1365-2133.2005.06642.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16029325">Naeem et al. (2005)</a> postulated that the mutation resulted in nonsense-mediated mRNA decay with complete absence of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16029325" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0013 ECTODERMAL DYSPLASIA 10B, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL RECESSIVE</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">rs797044437 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs797044437;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=rs797044437" 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=rs797044437" 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=RCV000006218 OR RCV001729338" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006218, RCV001729338" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006218...</a>
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<p>In an 18-year-old Lebanese woman with a severe form of autosomal recessive anhidrotic ectodermal dysplasia (ECTD10B; <a href="/entry/224900">224900</a>) with unusual clinical features including absence of breasts, extranumerary areola and nipple on the left side, and marked palmoplantar hyperkeratosis, <a href="#7" class="mim-tip-reference" title="Megarbane, H., Cluzeau, C., Bodemer, C., Fraitag, S., Chababi-Atallah, M., Megarbane, A., Smahi, A. <strong>Unusual presentation of a severe autosomal recessive anhydrotic (sic) ectodermal dysplasia with a novel mutation in the EDAR gene.</strong> Am. J. Med. Genet. 146A: 2657-2662, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18816645/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18816645</a>] [<a href="https://doi.org/10.1002/ajmg.a.32509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18816645">Megarbane et al. (2008)</a> identified a novel homozygous splice site mutation in the EDAR gene (IVS9+G-A). RT-PCR analysis performed on whole skin biopsies and genes known to be expressed in skin appendages indicated that the mutation severely impairs EDAR cDNA splicing, resulting in total absence of EDAR transcripts and consequently of the EDAR protein. <a href="#7" class="mim-tip-reference" title="Megarbane, H., Cluzeau, C., Bodemer, C., Fraitag, S., Chababi-Atallah, M., Megarbane, A., Smahi, A. <strong>Unusual presentation of a severe autosomal recessive anhydrotic (sic) ectodermal dysplasia with a novel mutation in the EDAR gene.</strong> Am. J. Med. Genet. 146A: 2657-2662, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18816645/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18816645</a>] [<a href="https://doi.org/10.1002/ajmg.a.32509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18816645">Megarbane et al. (2008)</a> stated that this was the first complete loss-of-function mutation identified in the EDAR gene, which may explain the unusual presentation of EDA in this patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18816645" 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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Chassaing, N., Bourthoumieu, S., Cossee, M., Calvas, P., Vincent, M.-C.
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<strong>Mutations in EDAR account for one-quarter of non-ED1-related hypohidrotic ectodermal dysplasia.</strong>
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Hum. Mutat. 27: 255-259, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16435307/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16435307</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16435307" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.20295" target="_blank">Full Text</a>]
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Doffinger, R., Smahi, A., Bessia, C., Geissmann, F., Feinberg, J., Durandy, A., Bodemer, C., Kenwrick, S., Dupuis-Girod, S., Blanche, S., Wood, P., Rabia, S. H., and 16 others.
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<strong>X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappa-B signaling.</strong>
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Nature Genet. 27: 277-285, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11242109/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11242109</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11242109" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/85837" target="_blank">Full Text</a>]
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Elomaa, O., Pulkkinen, K., Hannelius, U., Mikkola, M., Saarialho-Kere, U., Kere, J.
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<strong>Ectodysplasin is released by proteolytic shedding and binds to the EDAR protein.</strong>
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Hum. Molec. Genet. 10: 953-962, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11309369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11309369</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11309369" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Fujimoto, A., Kimura, R., Ohashi, J., Omi, K., Yuliwulandari, R., Batubara, L., Mustofa, M. S., Samakkarn, U., Settheetham-Ishida, W., Ishida, T., Morishita, Y., Furusawa, T., Nakazawa, M., Ohtsuka, R., Tokunaga, K.
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<strong>A scan for genetic determinants of human hair morphology: EDAR is associated with Asian hair thickness.</strong>
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Hum. Molec. Genet. 17: 835-843, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18065779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18065779</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18065779" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Fujimoto, A., Ohashi, J., Nishida, N., Miyagawa, T., Morishita, Y., Tsunoda, T., Kimura, R., Tokunaga, K.
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<strong>A replication study confirmed the EDAR gene to be a major contributor to population differentiation regarding head hair thickness in Asia.</strong>
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Hum. Genet. 124: 179-185, 2008.
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[<a href="https://doi.org/10.1007/s00439-008-0537-1" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/11943" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.32509" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s1359-6101(03)00020-0" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/11937" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.0600825103" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/humu.20795" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1365-2133.2005.06642.x" target="_blank">Full Text</a>]
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Sabeti, P. C., Varilly, P., Fry, B., Lohmueller, J., Hostetter, E., Cotsapas, C., Xie, X., Byrne, E. H., McCarroll, S. A., Gaudet, R., Schaffner, S. F., Lander, E. S., International HapMap Consortium.
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[<a href="https://doi.org/10.1038/nature06250" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.0022-202X.2004.23405.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.bbrc.2004.01.025" target="_blank">Full Text</a>]
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<a id="Trompouki2003" class="mim-anchor"></a>
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[<a href="https://doi.org/10.1038/nature01803" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/sj.ejhg.5202012" target="_blank">Full Text</a>]
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Yan, M., Wang, L.-C., Hymowitz, S. G., Schilbach, S., Lee, J., Goddard, A., de Vos, A. M., Gao, W.-Q., Dixit, V. M.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11039935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11039935</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11039935" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.290.5491.523" target="_blank">Full Text</a>]
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<span class="mim-text-font">
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Nara Sobreira - updated : 8/3/2009
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Cassandra L. Kniffin - updated : 3/11/2009<br>Cassandra L. Kniffin - updated : 2/19/2009<br>Patricia A. Hartz - updated : 10/31/2008<br>Cassandra L. Kniffin - updated : 9/5/2008<br>Cassandra L. Kniffin - updated : 7/2/2008<br>Ada Hamosh - updated : 2/21/2008<br>Patricia A. Hartz - updated : 7/28/2006<br>Victor A. McKusick - updated : 4/28/2006<br>Ada Hamosh - updated : 8/26/2003<br>George E. Tiller - updated : 10/2/2001<br>Ada Hamosh - updated : 3/1/2001<br>Ada Hamosh - updated : 10/30/2000
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carol : 08/04/2016<br>alopez : 08/03/2015<br>mcolton : 7/23/2015<br>carol : 11/20/2012<br>carol : 11/15/2012<br>alopez : 10/27/2009<br>carol : 8/3/2009<br>wwang : 3/18/2009<br>ckniffin : 3/11/2009<br>carol : 2/20/2009<br>carol : 2/20/2009<br>ckniffin : 2/19/2009<br>mgross : 11/14/2008<br>mgross : 11/14/2008<br>terry : 10/31/2008<br>wwang : 9/9/2008<br>ckniffin : 9/5/2008<br>wwang : 7/3/2008<br>ckniffin : 7/2/2008<br>carol : 2/28/2008<br>terry : 2/21/2008<br>terry : 2/21/2008<br>alopez : 6/18/2007<br>wwang : 4/3/2007<br>terry : 11/3/2006<br>wwang : 8/4/2006<br>terry : 7/28/2006<br>alopez : 5/2/2006<br>terry : 4/28/2006<br>alopez : 8/27/2003<br>alopez : 8/27/2003<br>terry : 8/26/2003<br>cwells : 10/10/2001<br>cwells : 10/2/2001<br>alopez : 3/2/2001<br>terry : 3/1/2001<br>mgross : 10/30/2000<br>alopez : 8/3/1999<br>alopez : 8/3/1999
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<h3>
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<span class="mim-font">
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<strong>*</strong> 604095
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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ECTODYSPLASIN A RECEPTOR; EDAR
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</span>
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</h3>
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</div>
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<br />
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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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<h4>
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<span class="mim-font">
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ECTODYSPLASIN 1, ANHIDROTIC RECEPTOR<br />
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DOWNLESS, MOUSE, HOMOLOG OF; DL<br />
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ECTODYSPLASIN A1 ISOFORM RECEPTOR<br />
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EDA-A1 RECEPTOR<br />
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EDA-A1R<br />
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EDA1R
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</h4>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: EDAR</em></strong>
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</p>
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<strong>
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<em>
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Cytogenetic location: 2q13
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Genomic coordinates <span class="small">(GRCh38)</span> : 2:108,894,471-108,989,220 </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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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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<th>
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Phenotype
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</th>
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Phenotype <br /> MIM number
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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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</thead>
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<tbody>
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<td rowspan="3">
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<span class="mim-font">
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2q13
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<td>
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<span class="mim-font">
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[Hair morphology 1, hair thickness]
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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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612630
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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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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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<tr>
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<td>
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<span class="mim-font">
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Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, 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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129490
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<span class="mim-font">
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Autosomal dominant
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<td>
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<span class="mim-font">
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3
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<tr>
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<td>
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<span class="mim-font">
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Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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224900
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</tbody>
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</table>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Hypohidrotic ectodermal dysplasia (HED) results in abnormal morphogenesis of teeth, hair, and eccrine sweat glands. Autosomal recessive forms of the disorder exist at 2 separate loci ('crinkled,' cr, and 'downless,' dl) in mice. A candidate gene has been identified at the dl locus that is mutated in both dl and Dl(sleek) (Dl(slk)) mutant alleles. Monreal et al. (1999) isolated and characterized EDAR, the human Dl homolog. The putative protein is predicted to have a single transmembrane domain, and shows similarity to 2 separate domains of the tumor necrosis factor (TNF; 191160) receptor (TNFR) family. The DL gene encodes a protein of 448 amino acids that is 91% identical to the mouse dl. The protein contains a single transmembrane domain with a type 1 membrane topology (extracellular amino terminus). </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>Yan et al. (2000) found that EDAR binds only EDA-A1 (see EDA; 300451), an ectodysplasin isoform that encodes a 391-amino acid protein with a domain similar to TNF at the C terminus. They examined the expression of EDAR in developing mouse skin by in situ hybridization. At embryonic day 14, EDAR transcripts were clearly present in the basal cells of the developing epidermis, with elevated focal expression in placodes. By embryonic days 16 and 17, EDAR was expressed in large amounts in the maturing follicles. By postnatal day 1, the pattern of expression was confined to the hair follicles. In addition, Yan et al. (2000) identified an X-linked ectodysplasin receptor, XEDAR (300276), that binds to the EDA-A2 isoform of EDA. EDA-A2 is identical to EDA-A1 except for a 2-residue deletion of glu308 and val309 that is caused by an internal splice donor site. </p><p>Doffinger et al. (2001) demonstrated that DL triggers NF-kappa-B (see 164011) through the NEMO protein (300248), indicating that anhidrotic ectodermal dysplasia results from impaired NF-kappa-B signaling. </p><p>Elomaa et al. (2001) showed that ectodysplasin is released from cells to the culture medium, and that EDAR is able to coprecipitate EDA-A1, confirming that they form a ligand-receptor pair. In situ hybridization and immunostaining demonstrated that ectodysplasin and EDAR are expressed in adjacent or partially overlapping layers in the developing human skin. The authors concluded that as a soluble ligand ectodysplasin is able to interact with EDAR and mediate signals needed for the development of ectodermal appendages. </p><p>Trompouki et al. (2003) identified CYLD (605018) as a deubiquitinating enzyme that negatively regulates activation of NF-kappa-B by specific TNFRs. Loss of the deubiquitinating activity of CYLD correlated with tumorigenesis. CYLD inhibits activation of NF-kappa-B by the TNFR family members CD40 (109535), XEDAR, and EDAR in a manner that depends on deubiquitinating activity of CYLD. Downregulation of CYLD by RNA-mediated interference augments both basal and CD40-mediated activation of NF-kappa-B. The inhibition of NF-kappa-B activation by CYLD is mediated, at least in part, by the deubiquitination and inactivation of TNFR-associated factor 2 (TRAF2; 601895) and, to a lesser extent, TRAF6 (602355). Trompouki et al. (2003) concluded that CYLD is a negative regulator of the cytokine-mediated activation of NF-kappa-B that is required for appropriate cellular homeostasis of skin appendages. </p><p>Using transfected human embryonic kidney cells and fibroblasts from mouse embryos defective in NF-kappa-B pathway components, Shindo and Chaudhary (2004) showed that EDAR signaling repressed LEF1 (153245)-beta-catenin (CTNNB1; 116806)-dependent transcription independent of its stimulatory effect on NF-kappa-B activity. Human EDAR with the arg420-to-gln (R420Q; 604095.0006) mutation associated with anhidrotic ectodermal dysplasia exhibited defects in both NF-kappa-B activation and LEF1/beta-catenin repression. In contrast, mouse Edar with a mutation associated with the downless phenotype retained significant ability to activate NF-kappa-B signaling and repress Lef1/beta-catenin activity. Shindo and Chaudhary (2004) concluded that, by stimulating NF-kappa-B activity and repressing LEF1/beta-catenin-dependent transcription, EDAR has opposing effects on 2 major and independent pathways involved in ectodermal differentiation and hair follicle morphogenesis. Since LEF1/beta-catenin controls expression of EDA, the results suggested negative feedback regulation of the EDA-EDAR axis. </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>Monreal et al. (1999) localized the EDAR gene to a position 10.1 cR from marker AFMA037YB9 between markers D2S293 and D2S121, an interval contained in chromosome 2q11-q13. Autosomal recessive hypohidrotic ectodermal dysplasia (HED; 224900) does not map to the candidate gene locus in all families, implying the existence of at least 1 additional human locus. </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>Evolution</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>Sabeti et al. (2007) reported an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2. The analysis revealed more than 300 strong candidate regions that appeared to have undergone recent natural selection. Examination of 22 of the strongest regions highlighted 3 cases in which 2 genes in a common biologic process had apparently undergone positive selection in the same population: LARGE (603590) and DMD (300377), both related to infection by the Lassa virus, in West Africa; SLC24A5 (609802) and SLC45A2 (606202), both involved in skin pigmentation, in Europe; and EDAR and EDA2R (300276), both involved in the development of hair follicles, in Asia. </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>Monreal et al. (1999) identified mutations in the DL gene in 3 families displaying recessive inheritance of HED (ECTD10B; 224900) and 2 with dominant inheritance (ECTD10A; 129490). They identified 7 variants, 2 of which were detected in the control population. A single change involving a basepair transition in exon 12 (arg358 to ter, 604095.0005; arg420 to gln, 604095.0006) was found in each dominant family. The arg358-to-ter mutation resulted in a truncation of the predicted cytoplasmic portion of the protein, similar to the effect of the dominant mutation Dl(slk) in the mouse, which truncates the protein before the possible death domain. It had been shown that coexpression of a truncated TNFR with a wildtype receptor results in a dominant-negative effect on function, presumably due to lack of homotrimerization of the death domains. Dominant-negative mutations have also been described in the FAS antigen (134637), a member of the TNFR family, in patients with autoimmune lymphoproliferative syndrome (601859). The nonconserved missense mutation arg420 to gln in a second family was also in the predicted cytoplasmic portion of the protein within the potential death domain. Monreal et al. (1999) showed that DL mutations produce recessive loss-of-function, as well as likely dominant-negative, effects. One hypothesis is that the protein functions as a multimeric receptor and is related to the TNFR family. The authors noted that ectodysplasin-A, the protein abnormal in X-linked hypohidrotic ectodermal dysplasia, shows a highly significant match in its extracellular domain with the TNF family profile. Further study will be required to test if DL and ectodysplasin-A proteins function as receptor and ligand in a common signaling pathway. </p><p>To assess the role of the EDAR gene in HED, Chassaing et al. (2006) screened for mutations in 37 unrelated HED families or sporadic cases with no detected mutations in the EDA gene (300451). They identified 11 different mutations, 9 of which were novel variants, in 2 familial and 7 sporadic cases. Seven of the 11 were recessive and the other 4 were considered to be probably dominant. The study demonstrated that EDAR is implicated in about 25% of non-EDA HED. They diagrammed the process by which, during hair follicle morphogenesis, EDAR is activated by the product of the EDA gene and uses EDARADD (606603) as an adaptor to activate the NF-kappa-B (see 164011) signaling pathway (Mikkola and Thesleff, 2003). </p><p>In an 18-year-old Lebanese woman with a severe form of autosomal recessive anhidrotic ectodermal dysplasia with unusual clinical features including absence of breasts, extranumerary areola and nipple on the left side, and marked palmoplantar hyperkeratosis, Megarbane et al. (2008) identified a novel homozygous splice site mutation in the EDAR gene (IVS9+G-A; 604095.0013). RT-PCR analysis performed on whole skin biopsies and genes known to be expressed in skin appendages indicated that the mutation severely impairs EDAR cDNA splicing, resulting in total absence of EDAR transcripts and consequently of the EDAR protein. Megarbane et al. (2008) hypothesized that the mutation leads to the loss of EDAR/NF-kappa-B signaling. They speculated that the mutation impairs Wnt (see 164820)/B-catenin (116806) downregulation, which may modify the balance between signals necessary to mammary gland development. </p><p>Fujimoto et al. (2008) identified a mutation in the EDAR gene associated with variation in hair thickness (604095.0011). </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>Headon and Overbeek (1999) used positional cloning to identify the mouse dl gene, which encodes a novel member of the tumor necrosis factor receptor family. The mutant phenotype and dl expression pattern suggested that this gene encodes a receptor that specifies hair follicle fate. Its ligand is likely to be the product of the 'Tabby' gene, as Ta mutants have a phenotype identical to that of dl mutants and Ta encodes a tumor necrosis factor receptor-like protein. Northern blot analysis of mRNA from embryonic day 17.5 skin revealed a 3.8-kb transcript in all genotypes except Dl(slk) and dl(OVE1B). At embryonic day 13, before hair follicle induction, dl is expressed throughout the basal layer of the epidermis. By embryonic day 15, expression has become upregulated in foci of induced cells initiating and undergoing follicular morphogenesis and is beginning to be downregulated in surrounding cells. By embryonic day 17, dl is expressed in secondary follicles and elongating primary follicles, but is no longer detected in the interfollicular epidermis. There was an absence of expression of early hair follicle markers, including Bmp4 and Shh, in dl mutant skin. </p><p>By examining embryonic mouse skin cultures, Mou et al. (2006) determined that Edar is central to the generation of the primary hair follicle pattern. They found a rapid Edar-positive feedback mechanism in the epidermis coupled with induction of dermal Bmp4 (112262) and Bmp7 (112267), which repressed epidermal Edar expression and follicle fate in cells neighboring nascent follicles. Edar activation also induced connective tissue growth factor (CTGF; 121009), an inhibitor of BMP signaling, allowing BMP action only at a distance from nascent follicles. Consistent with this mode, transgenic hyperactivation of Edar signaling led to widespread overproduction of hair follicles. Edar-mediated stabilization of beta-catenin (see CTNNB1, 116806)-active foci appeared to be a key event in determining follicle location. </p><p>Mou et al. (2008) found that mice with overexpression of the Edar gene displayed a coarser coat hair phenotype compared to wildtype mice. The diameter of each hair type was increased by 10 to 25% upon elevation of Edar signaling, corresponding to an increase of cross-sectional area of 21 to 56%. In addition, the hair of transgenic mice showed increased straightness and a more circular cross-section appearance. Primary hair follicles of the transgenic mice showed an enlarged bulb region with Edar expression within the bulb, and transgenic mouse embryos showed larger hair follicle placodes, which represent the organ primordia. Mou et al. (2008) commented that the phenotype was similar to that observed in East Asian human hair, which is thicker and more circular on cross-section profile and is associated with a SNP in the EDAR gene (604095.0011) that causes increased downstream NFKB activity. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>13 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 ECTODERMAL DYSPLASIA 10B, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL RECESSIVE</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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EDAR, 18-BP DEL, IVS2
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<br />
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SNP: rs1558814967,
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ClinVar: RCV000006205
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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 consanguineous family with autosomal recessive hypohidrotic ectodermal dysplasia (ECTD10B; 224900), Monreal et al. (1999) identified an 18-bp deletion at the 3-prime end of intron 2 of the EDAR gene. The deletion altered 7 of 10 basepairs constituting a polypyrimidine stretch at the acceptor splice site, reducing the number of pyrimidines from 8 to 3. </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 ECTODERMAL DYSPLASIA 10B, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL RECESSIVE</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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ECTODERMAL DYSPLASIA 10A, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL DOMINANT, INCLUDED
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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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EDAR, ARG89HIS
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<br />
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SNP: rs121908450,
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gnomAD: rs121908450,
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ClinVar: RCV000006206, RCV000032598, RCV000681480, RCV001038628, RCV001253315
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 affected sibs from a nonconsanguineous family with autosomal recessive hypohidrotic ectodermal dysplasia (ECTD10B; 224900), Monreal et al. (1999) detected a G-to-A transition at nucleotide 266 of the EDAR gene resulting in a nonconservative change of arg89 to his in the extracellular domain. The affected children were heterozygous at flanking polymorphic loci, but failed to inherit a paternal allele at the D2S1893 locus. Sequencing revealed their mother to be heterozygous for the variant, whereas their father was hemizygous wildtype. Thus, the affected individuals were compound heterozygotes, with their paternal allele containing a large deletion of indeterminate size (see 604095.0003). </p><p>Van der Hout et al. (2008) reported 2 brothers with hypohidrotic ectodermal dysplasia resulting from compound heterozygosity for the R89H and D110A (604095.0009) mutations in the EDAR gene. The unaffected father carried the D110A mutation. However, the mother, who was heterozygous for the R89H mutation, was mildly affected with hypohidrosis and few permanent teeth, consistent with autosomal dominant hypohidrotic ectodermal dysplasia (ECTD10A; 129490). Van der Hout et al. (2008) concluded that some presumably 'recessive' mutations may show phenotypic expression in carriers. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 ECTODERMAL DYSPLASIA 10B, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL RECESSIVE</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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EDAR, DEL
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<br />
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ClinVar: RCV000006208
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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>For discussion of the large deletion of indeterminate size that was found in the EDAR gene in compound heterozygous state in 2 sibs with autosomal recessive hypohidrotic ectodermal dysplasia (ECTD10B; 224900) by Monreal et al. (1999), see 604095.0002. </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>.0004 ECTODERMAL DYSPLASIA 10B, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL RECESSIVE</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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EDAR, CYS87ARG
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<br />
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SNP: rs121908451,
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gnomAD: rs121908451,
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ClinVar: RCV000006209, RCV003764531
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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 family with autosomal recessive hypohidrotic ectodermal dysplasia (ECTD10B; 224900), Monreal et al. (1999) identified a homozygous T-to-C transition at nucleotide 259 of the EDAR gene resulting in a cys-to-arg substitution at codon 87 (C87R) in affected individuals. The mutation resulted in a nonconservative change in the extracellular domain, possibly affecting intra- or interchain disulfide bond formation. </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>
|
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<span class="mim-font">
|
|
<strong>.0005 ECTODERMAL DYSPLASIA 10A, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL DOMINANT</strong>
|
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</span>
|
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</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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EDAR, ARG358TER
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<br />
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SNP: rs121908452,
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ClinVar: RCV000006210, RCV000255664, RCV000532015, RCV001261883, RCV003505080
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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 family with autosomal dominant hypohidrotic ectodermal dysplasia (ECTD10A; 129490), Monreal et al. (1999) identified a C-to-T transition at nucleotide 1072 in exon 12 of the EDAR gene resulting in an arg-to-ter substitution at codon 358 (R358X). This mutation was found in heterozygosity in all affected individuals. The mutation resulted in a truncation of the predicted cytoplasmic portion of the protein, similar to the effect of the dominant mutation Dl(slk) in the mouse, which truncates the protein before the possible death domain. </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 ECTODERMAL DYSPLASIA 10A, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL DOMINANT</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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EDAR, ARG420GLN
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<br />
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SNP: rs121908453,
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ClinVar: RCV000006211, RCV000255701, RCV000755721, RCV001050412, RCV001334149
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|
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In all affected members of a family with autosomal dominant hypohidrotic ectodermal dysplasia (ECTD10A; 129490), Monreal et al. (1999) identified a G-to-A transition at nucleotide 1259 in exon 12 of the EDAR gene that resulted in an arg-to-gln substitution at codon 420 (R420Q). </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>
|
|
<span class="mim-font">
|
|
<strong>.0007 ECTODERMAL DYSPLASIA 10B, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL RECESSIVE</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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EDAR, IVS2DS, G-A, +1
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<br />
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SNP: rs797044435,
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ClinVar: RCV000006212
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese woman with autosomal recessive hypohidrotic ectodermal dysplasia (ECTD10B; 224900), Shimomura et al. (2004) identified compound heterozygosity for 2 mutations in the EDAR gene: a G-to-A transition in intron 2, resulting in an unstable transcript lacking exon 2, and a 1124G-A transition in exon 12, resulting in an arg375-to-his (R375H; 604095.0008) substitution within the intracellular DD domain. The patient's unaffected father carried the R375H mutation. In vitro functional expression studies showed that the R375H mutant protein did not interact with EDARADD (606603) and was functionally inactive. The patient had heat intolerance, sparse hair, periorbital wrinkling, and oligodontia. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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|
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</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 ECTODERMAL DYSPLASIA 10B, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
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|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
EDAR, ARG375HIS
|
|
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|
|
<br />
|
|
|
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SNP: rs121908454,
|
|
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|
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gnomAD: rs121908454,
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|
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ClinVar: RCV000006213
|
|
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|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg357-to-his (R357H) mutation in the EDAR gene that was found in compound heterozygous state in a patient with autosomal recessive hypohidrotic ectodermal dysplasia (ECTD10B; 224900) by Shimomura et al. (2004), see 604095.0007. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
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</div>
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</div>
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<div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 ECTODERMAL DYSPLASIA 10B, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
EDAR, ASP110ALA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908455,
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|
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|
|
gnomAD: rs121908455,
|
|
|
|
|
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ClinVar: RCV000006214
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 brothers with autosomal recessive hypohidrotic ectodermal dysplasia (ECTD10B; 224900), van der Hout et al. (2008) identified compound heterozygosity for 2 mutations in the EDAR gene: a 329A-C transversion in exon 4 resulting in an asp110-to-ala (D110A) substitution and the R89H (604095.0002) mutation. The unaffected father was heterozygous for the D110A mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
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|
<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 ECTODERMAL DYSPLASIA 10A, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
EDAR, GLU354TER
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs121908456,
|
|
|
|
|
|
|
|
ClinVar: RCV000006215
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a woman with autosomal dominant hypohidrotic ectodermal dysplasia (ECTD10A; 129490), van der Hout et al. (2008) identified a heterozygous 1060G-T transversion in exon 12 of the EDAR gene, resulting in a glu354-to-ter (E354X) substitution. Her son was also affected but was not tested for the mutation. </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 HAIR MORPHOLOGY 1, HAIR THICKNESS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
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<span class="mim-text-font">
|
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|
|
EDAR, VAL370ALA
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<br />
|
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|
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SNP: rs3827760,
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|
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gnomAD: rs3827760,
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|
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ClinVar: RCV000006216, RCV000174399, RCV000382959, RCV001133945, RCV001261884, RCV001523395, RCV001659684, RCV001659685, RCV001723544
|
|
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>Fujimoto et al. (2008) identified a 1540T-C SNP (rs3827760) in exon 12 of the EDAR gene, resulting in a val370-to-ala (V370A) substitution in the intracellular death domain. The C allele was present at a frequency of 87.6% in 180 Chinese and Japanese samples, compared to 0% in 120 European and African samples. A further study of 121 unrelated Indonesian individuals from the Java Island and 65 unrelated individuals of the Thai-Mai in Thailand showed a significant association of the 1540T/C SNP with cross-sectional area of hairs (612630) (p = 5.5 x 10(-3) and p = 9.5 x 10(-4), for the populations, respectively). In vitro functional expression studies showed that the C allele of this SNP in EDAR resulted in decreased downstream activity of NFKB (see 164011) 48 hours after transfection into HeLa cells. By studying the geographic distribution of the 1540T/C SNP in the EDAR gene and using haplotype analysis, Fujimoto et al. (2008) concluded that the 1540C allele arose after the divergence of Asians from Europeans, and that its frequency has rapidly increased in East Asian populations due to positive selection. </p><p>In a follow-up study, Fujimoto et al. (2008) found a significant association between 1540C and increased hair cross-sectional area in a cohort of 189 Japanese individuals (p = 2.7 x 10(-6)). A stronger association was noted (p = 3.8 x 10(-10)) when the findings were combined with population results of the Thai-Mai and Indonesian cohorts from the previous study. The findings confirmed that EDAR is the genetic determinant of hair thickness, as well as a strong contributor to hair fiber thickness variation, in East Asian populations. </p><p>In contrast to the findings of Fujimoto et al. (2008), Mou et al. (2008) found that the C allele (ala370) resulted in increased downstream activity of NFKB in transfected human cells after 18 hours. Mou et al. (2008) stated that their results more accurately reflected physiologic conditions. </p><p>For discussion of a possible association between the T1540C polymorphism and shovel-shaped incisors, see 147400.</p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 ECTODERMAL DYSPLASIA 10B, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
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<span class="mim-text-font">
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EDAR, 4-BP DEL, 718AAAG
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<br />
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SNP: rs797044436,
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|
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ClinVar: RCV000006217
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</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a consanguineous Pakistani family with autosomal recessive hypohidrotic ectodermal dysplasia (ECTD10B; 224900), Naeem et al. (2005) identified a homozygous 4-bp deletion (718delAAAG) in exon 8 of the EDAR gene, resulting in a frameshift and premature termination. Affected individuals had classic features of the disorder, including sparse hair, absent eyebrows and eyelashes, missing teeth, decreased sweating, dry thin skin, periorbital wrinkling and hyperpigmentation, prominent lips, and a saddle-shaped nose. Heterozygous gene carriers were not affected. Naeem et al. (2005) postulated that the mutation resulted in nonsense-mediated mRNA decay with complete absence of the protein. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
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</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 ECTODERMAL DYSPLASIA 10B, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
EDAR, IVS9, G-A, +1
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs797044437,
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|
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|
|
ClinVar: RCV000006218, RCV001729338
|
|
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|
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</span>
|
|
</div>
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|
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 18-year-old Lebanese woman with a severe form of autosomal recessive anhidrotic ectodermal dysplasia (ECTD10B; 224900) with unusual clinical features including absence of breasts, extranumerary areola and nipple on the left side, and marked palmoplantar hyperkeratosis, Megarbane et al. (2008) identified a novel homozygous splice site mutation in the EDAR gene (IVS9+G-A). RT-PCR analysis performed on whole skin biopsies and genes known to be expressed in skin appendages indicated that the mutation severely impairs EDAR cDNA splicing, resulting in total absence of EDAR transcripts and consequently of the EDAR protein. Megarbane et al. (2008) stated that this was the first complete loss-of-function mutation identified in the EDAR gene, which may explain the unusual presentation of EDA in this patient. </p>
|
|
</span>
|
|
</div>
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<div>
|
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<br />
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</div>
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</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
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