3621 lines
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Entry
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- *302910 - CHLORIDE CHANNEL 4; CLCN4
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- OMIM
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<p>
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<span class="h4">*302910</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#evolution">Evolution</a>
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<a href="#history">History</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/302910">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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<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 role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div 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 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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<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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<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=ENSG00000073464;t=ENST00000380833" 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=1183" 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=302910" 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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<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=ENSG00000073464;t=ENST00000380833" 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_001256944,NM_001830" 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_001830" 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=302910" 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=02362&isoform_id=02362_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/CLCN4" 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/479159,3399663,4760533,5759112,20141247,71051499,119619183,119619184,120660006,153252026,158260151,221042806,379643013" 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/P51793" 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=1183" 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=ENSG00000073464;t=ENST00000380833" 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=CLCN4" 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=CLCN4" 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+1183" 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/CLCN4" 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:1183" 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/1183" 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=chrX&hgg_gene=ENST00000380833.9&hgg_start=10156975&hgg_end=10237660&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:2022" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:2022" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=302910[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=302910[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/CLCN4/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/ENSG00000073464" 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.gwascentral.org/search?q=CLCN4" 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=CLCN4" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://www.LOVD.nl/CLCN4" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=CLCN4&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/PA26549" 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:2022" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0036566.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:104571" 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/CLCN4#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:104571" 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/1183/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=1183" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00000532;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-061013-353" 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:1183" 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=CLCN4&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 1172691004<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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302910
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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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CHLORIDE CHANNEL 4; CLCN4
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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">
|
|
CHLORIDE CHANNEL, VOLTAGE-GATED, 4
|
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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">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=CLCN4" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CLCN4</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/X/53?start=-3&limit=10&highlight=53">Xp22.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chrX:10156975-10237660&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'})">X:10,156,975-10,237,660</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>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
|
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<th>
|
|
Location
|
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</th>
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<th>
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Phenotype
|
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
|
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</th>
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<th>
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Phenotype <br /> mapping key
|
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</th>
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</tr>
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</thead>
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<tbody>
|
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|
<tr>
|
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<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/X/53?start=-3&limit=10&highlight=53">
|
|
Xp22.2
|
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</a>
|
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</span>
|
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</td>
|
|
|
|
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<td>
|
|
<span class="mim-font">
|
|
Raynaud-Claes syndrome
|
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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/300114"> 300114 </a>
|
|
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="X-linked dominant">XLD</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/302910" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/302910" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<p>CLCN4 is a voltage-gated chloride channel (<a href="#14" class="mim-tip-reference" title="van Slegtenhorst, M. A., Bassi, M. T., Borsani, G., Wapenaar, M. C., Ferrero, G. B., de Conciliis, L., Rugarli, E. I., Grillo, A., Franco, B., Zoghbi, H. Y., Ballabio, A. <strong>A gene from the Xp22.3 region shares homology with voltage-gated chloride channels.</strong> Hum. Molec. Genet. 3: 547-552, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8069296/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8069296</a>] [<a href="https://doi.org/10.1093/hmg/3.4.547" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8069296">van Slegtenhorst et al., 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8069296" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In the course of constructing a comprehensive transcript map of the Xp22.3 region, <a href="#14" class="mim-tip-reference" title="van Slegtenhorst, M. A., Bassi, M. T., Borsani, G., Wapenaar, M. C., Ferrero, G. B., de Conciliis, L., Rugarli, E. I., Grillo, A., Franco, B., Zoghbi, H. Y., Ballabio, A. <strong>A gene from the Xp22.3 region shares homology with voltage-gated chloride channels.</strong> Hum. Molec. Genet. 3: 547-552, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8069296/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8069296</a>] [<a href="https://doi.org/10.1093/hmg/3.4.547" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8069296">van Slegtenhorst et al. (1994)</a> identified an evolutionarily conserved CpG island and cloned the corresponding gene. The predicted 760-amino acid protein contained 12 hydrophobic domains and shared sequence and structural similarities with all the previously isolated members of the family of voltage-gated chloride channels. In contrast with most genes isolated from the Xp22.3 region, CLCN4 did not share homology with the Y chromosome, but was conserved in mouse and hamster. Expression studies demonstrated a 7.5-kb transcript that is particularly abundant in skeletal muscle and also detectable in brain and heart. Thus, this gene encodes a newly identified voltage-gated chloride channel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8069296" 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="#7" class="mim-tip-reference" title="Nguyen, D. K., Yang, F., Kaul, R., Alkan, C., Antonellis, A., Friery, K. F., Zhu, B., de Jong, P. J., Disteche, C. M. <strong>Clcn4-2 genomic structure differs between the X locus in Mus spretus and the autosomal locus in Mus musculus: AT motif enrichment on the X.</strong> Genome Res. 21: 402-409, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21282478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21282478</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21282478[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/10.1101/gr.108563.110" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21282478">Nguyen et al. (2011)</a> compared the CLCN4 exon/intron structure of 8 mammalian species. In all species examined, the ATG translation start site was located at the beginning of exon 3, and the poly(A) tail was within exon 13. The coding sequence of exons 3 to 13 was highly conserved, with an overall 80 to 90% identity between species. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21282478" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The CLCN4 gene maps to chromosome Xp22.3 (<a href="#14" class="mim-tip-reference" title="van Slegtenhorst, M. A., Bassi, M. T., Borsani, G., Wapenaar, M. C., Ferrero, G. B., de Conciliis, L., Rugarli, E. I., Grillo, A., Franco, B., Zoghbi, H. Y., Ballabio, A. <strong>A gene from the Xp22.3 region shares homology with voltage-gated chloride channels.</strong> Hum. Molec. Genet. 3: 547-552, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8069296/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8069296</a>] [<a href="https://doi.org/10.1093/hmg/3.4.547" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8069296">van Slegtenhorst et al., 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8069296" 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="#12" class="mim-tip-reference" title="Rugarli, E. I., Adler, D. A., Borsani, G., Tsuchiya, K., Franco, B., Hauge, X., Disteche, C., Chapman, V., Ballabio, A. <strong>Different chromosomal localization of the Clcn4 gene in Mus spretus and C57BL/6J mice.</strong> Nature Genet. 10: 466-471, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670496/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670496</a>] [<a href="https://doi.org/10.1038/ng0895-466" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7670496">Rugarli et al. (1995)</a> found that in the wild Mediterranean mouse Mus spretus, the Cln4 gene maps to the X chromosome as it does in the human; however, in the inbred strain of laboratory mouse C57BL/6J, they found that it maps to chromosome 7. Findings indicated that a recent evolutionary rearrangement occurred in the mouse sex chromosomes very close to the pseudoautosomal region (PAR). The data were considered molecular evidence for a major divergence near the pseudoautosomal region consistent with the hypothesis that hybrid sterility in these species results from abnormal pairing of sex chromosomes during male meiosis. They found that Cln4 is the closest cloned gene to the M. spretus pseudoautosomal region and the most distal locus displaying a conserved position between the human and this mouse locus. The X-inactivation status of the locus in M. spretus was demonstrated by the finding that in F1 females from a cross between M. spretus and an inbred-derived mouse carrying the t(X;16)16H balanced translocation, it was always the normal M. spretus X chromosome that was inactive in adult tissues. This completely skewed X inactivation provided a system for assaying expression of genes from the inactive X chromosome once the parental alleles could be distinguished. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7670496" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Palmer, S., Perry, J., Ashworth, A. <strong>A contravention of Ohno's law in mice.</strong> Nature Genet. 10: 472-476, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670497/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670497</a>] [<a href="https://doi.org/10.1038/ng0895-472" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7670497">Palmer et al. (1995)</a> likewise found what they referred to as 'contravention of Ohno's law' in the course of mapping a cDNA mouse Cln4 in an interspecific backcross. This was the first example of a gene unique to the X chromosome in 1 eutherian species but autosomal in another. The consequence of this chromosomal rearrangement was that the gene was lost by mendelian segregation in a subset of the male progeny of a (C57BL/6 x Mus spretus) x Mus spretus backcross. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7670497" 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 14-month-old boy with Raynaud-Claes syndrome (MRXSRC; <a href="/entry/300114">300114</a>) who presented with epileptic encephalopathy, <a href="#15" class="mim-tip-reference" title="Veeramah, K. R., Johnstone, L., Karafet, T. M., Wolf, D., Sprissler, R., Salogiannis, J., Barth-Maron, A., Greenberg, M. E., Stuhlmann, T., Weinert, S., Jentsch, T. J., Pazzi, M., Restifo, L. L., Talwar, D., Erickson, R. P., Hammer, M. F. <strong>Exome sequencing reveals new causal mutations in children with epileptic encephalopathies.</strong> Epilepsia 54: 1270-1281, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23647072/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23647072</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23647072[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/10.1111/epi.12201" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23647072">Veeramah et al. (2013)</a> identified a de novo hemizygous missense mutation in the CLCN4 gene (G544R; <a href="#0001">302910.0001</a>). The mutation was found by whole-exome sequencing. In vitro functional expression studies in Xenopus oocytes showed that the mutation almost abolished the outwardly rectifying currents, consistent with a loss of function. The patient was 1 of 10 probands with a similar phenotype who underwent whole-exome sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23647072" 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 affected male members of 5 unrelated families with X-linked intellectual disability, including the family (MRX49) reported by <a href="#1" class="mim-tip-reference" title="Claes, S., Vogels, A., Holvoet, M., Devriendt, K., Raeymaekers, P., Cassiman, J. J., Fryns, J. P. <strong>Regional localization of two genes for nonspecific X-linked mental retardation to Xp22.3-p22.2 (MRX49) and Xp11.3-p11.21 (MRX50).</strong> Am. J. Med. Genet. 73: 474-479, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9415477/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9415477</a>]" pmid="9415477">Claes et al. (1997)</a> and the family (MRX15) reported by <a href="#11" class="mim-tip-reference" title="Raynaud, M., Gendrot, C., Dessay, B., Moncla, A., Ayrault, A.-D., Moizard, M.-P., Toutain, A., Briault, S., Villard, L., Ronce, N., Moraine, C. <strong>X-linked mental retardation with neonatal hypotonia in a French family (MRX15): gene assignment to Xp11.22-Xp21.1.</strong> Am. J. Med. Genet. 64: 97-106, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8826458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8826458</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1<97::AID-AJMG17>3.0.CO;2-N" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8826458">Raynaud et al. (1996)</a>, <a href="#5" class="mim-tip-reference" title="Hu, H., Haas, S. A., Chelly, J., Van Esch, H., Raynaud, M., de Brouwer, A. P. M., Weinert, S., Froyen, G., Frints, S. G. M., Laumonnier, F., Zemojtel, T., Love, M. I., and 72 others. <strong>X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes.</strong> Molec. Psychiat. 21: 133-148, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25644381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25644381</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25644381[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/mp.2014.193" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25644381">Hu et al. (2016)</a> identified hemizygous mutations in the CLCN4 gene (<a href="#0002">302910.0002</a>-<a href="#0006">302910.0006</a>). The mutations were found by X-chromosome exome sequencing. One of the mutations resulted in a truncated protein, whereas the 4 others were missense mutations. In vitro functional expression studies in Xenopus oocytes showed that all of the missense mutations caused a marked reduction in outwardly-rectifying CLCN4 currents compared to wildtype. Knockdown of the Clcn4 gene in mouse hippocampal neurons resulted in 30% less dendritic branches compared to controls, and primary neurons derived from Clcn4-null mice showed similar, but more subtle, changes. The findings were consistent with a loss of function underlying the cognitive defects in these families. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8826458+9415477+25644381" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Palmer, E. E., Stuhlmann, T., Weinert, S., Haan, E., Van Esch, H., Holvoet, M., Boyle, J., Leffler, M., Raynaud, M., Moraine, C., van Bokhove, H., Kleefstra, T., and 38 others. <strong>De novo and inherited mutations in the X-linked gene CLCN4 are associated with syndromic intellectual disability and behavior and seizure disorders in males and females.</strong> Molec. Psychiat. 23: 222-230, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27550844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27550844</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27550844[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/mp.2016.135" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27550844">Palmer et al. (2018)</a> summarized phenotypic and molecular genetic information on 52 individuals from 16 families with a syndromic intellectual disability disorder, including 6 previously reported families, and mutation in the CLCN4 gene. In 5 affected females (see, e.g., <a href="#0007">302910.0007</a>) and 2 affected males, the mutations occurred de novo. The mutation spectrum included frameshift, missense, and splice site variants, and one single-exon deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27550844" 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 his classic monograph entitled 'Sex Chromosomes and Sex-Linked Genes,' <a href="#8" class="mim-tip-reference" title="Ohno, S. <strong>Sex Chromosomes and Sex-linked Genes.</strong> Berlin and New York: Springer (pub.) 1967."None>Ohno (1967)</a> promulgated his famous law based on numerous examples of conservation of X-linked genes, cementing the concept of the X chromosome in placental mammals as an immutable element (<a href="#3" class="mim-tip-reference" title="Ellis, N. A. <strong>Ecce Ohno.</strong> Nature Genet. 10: 373-375, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670482/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670482</a>] [<a href="https://doi.org/10.1038/ng0895-373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7670482">Ellis, 1995</a>). Motivating most of Ohno's thesis was the compelling but complex evolutionary argument that heteromorphic sex chromosomes in mammals evolved originally from a pair of homomorphic autosomes. Mutations occurred in 2 (or more) genes on 1 of these chromosomes (the proto-Y chromosome) but caused the genes to become factors in the sexual differentiation of the male. These genes had to segregate together; thus, recombination was suppressed between the incipient sex chromosomes. As a consequence of recombination suppression, the proto-Y chromosome suffered gradual genetic deterioration that eventually left it a 'dummy chromosome.' At the same time, a dosage compensation mechanism evolved that doubled the rate of product output of X-linked genes (because monosomy is deleterious) and led to the inactivation of the extra X chromosome in females. The X-chromosome inactivation mechanism became an evolutionary barrier to the shuffling of genes between the X and autosomes because, as had previously been shown, such rearrangements disrupt the compensation mechanism. Laxity in Ohno's law was previously discovered in relation to the pseudoautosomal region in which DNA segments of the X and Y pair and show crossing-over, generally presumed to be necessary for the proper segregation of the X and Y chromosomes. Genes in the PAR escape X inactivation which removes them from the evolutionary force that would retain them on the X chromosome. The genes that are known to be in the PAR include ASMT (<a href="/entry/300015">300015</a>) and ASMTY (<a href="/entry/402500">402500</a>); the first such gene to be discovered, MIC2 (<a href="/entry/313470">313470</a>) and MIC2Y (<a href="/entry/450000">450000</a>); the XG blood group gene (<a href="/entry/300879">300879</a> and XGPY); IL3RA (<a href="/entry/308385">308385</a>) and IL3RAY (<a href="/entry/430000">430000</a>); AMELX (<a href="/entry/300391">300391</a>) and AMELY (<a href="/entry/410000">410000</a>); CSF2RA (<a href="/entry/306250">306250</a>) and CSF2RY (<a href="/entry/425000">425000</a>); and ANT3 (<a href="/entry/300151">300151</a>) and ANT3Y (<a href="/entry/403000">403000</a>). Consistent with this laxity, syntenic conservation of genes in the PAR is not a hard and fast rule. For example, CSF2RA and IL3RA are pseudoautosomal in the human and autosomal in the mouse; see <a href="#2" class="mim-tip-reference" title="Disteche, C. M., Brannan, C. I., Larsen, A., Adler, D. A., Schorderet, D. F., Gearing, D., Copeland, N. G., Jenkins, N. A., Park, L. S. <strong>The human pseudoautosomal GM-CSF receptor alpha subunit gene is autosomal in mouse.</strong> Nature Genet. 1: 333-336, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1363815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1363815</a>] [<a href="https://doi.org/10.1038/ng0892-333" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1363815">Disteche et al. (1992)</a> and <a href="#6" class="mim-tip-reference" title="Milatovich, A., Kitamura, T., Miyajima, A., Francke, U. <strong>Gene for the alpha-subunit of the human interleukin-3 receptor (IL3RA) localized to the X-Y pseudoautosomal region.</strong> Am. J. Hum. Genet. 53: 1146-1153, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8213838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8213838</a>]" pmid="8213838">Milatovich et al. (1993)</a>, respectively. A further wrinkle on the evolution of this region of the X chromosome is demonstrated by the steroid sulfatase gene (STS; <a href="/entry/300747">300747</a>), which escapes X inactivation in both humans and the mouse but is X-linked in humans while pseudoautosomal in the mouse. The PAR has been implicated in the mouse and perhaps in other species in providing an explanation for Haldane's rule (<a href="#4" class="mim-tip-reference" title="Haldane, J. B. S. <strong>Sex ratio and unisexual sterility in hybrid animals.</strong> J. Genet. 12: 101-109, 1922."None>Haldane, 1922</a>) that in interspecific hybrids, the heterogametic sex of the F1 offspring is absent, rare, or sterile. In crosses between M. spretus and M. musculus, the male F1 offspring are sterile. Their testes are small, probably due to breakdown of spermatogenesis after meiosis 1. Almost all X-Y bivalents dissociate by diakinesis, probably because of the failure of the sex chromosomes from the 2 different species to pair and recombine properly. Lack of homology between the PARs may be the underlying cause. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1363815+7670482+8213838" 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="Schnur, R. E., Wick, P. A. <strong>Intragenic TaqI restriction fragment length polymorphism (RFLP) in CLCN4, between the loci for X-linked ocular albinism (OA1) and microphthalmia with linear skin defects syndrome (MLS).</strong> Hum. Genet. 95: 594-595, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7759088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7759088</a>] [<a href="https://doi.org/10.1007/BF00223880" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7759088">Schnur and Wick (1995)</a> detected a TaqI RFLP within the CLCN4 gene which lies between the loci for ocular albinism (OA1; <a href="/entry/300500">300500</a>) and microphthalmia with linear skin defects (MLS; <a href="/entry/309801">309801</a>). No recombination was observed between the RFLP and the OA1 mutation in 3 informative families, indicating that the marker would be useful for genetic counseling in OA1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7759088" 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 14-month-old boy with Raynaud-Claes syndrome (MRXSRC; <a href="/entry/300114">300114</a>) who presented with epileptic encephalopathy, <a href="#15" class="mim-tip-reference" title="Veeramah, K. R., Johnstone, L., Karafet, T. M., Wolf, D., Sprissler, R., Salogiannis, J., Barth-Maron, A., Greenberg, M. E., Stuhlmann, T., Weinert, S., Jentsch, T. J., Pazzi, M., Restifo, L. L., Talwar, D., Erickson, R. P., Hammer, M. F. <strong>Exome sequencing reveals new causal mutations in children with epileptic encephalopathies.</strong> Epilepsia 54: 1270-1281, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23647072/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23647072</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23647072[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/10.1111/epi.12201" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23647072">Veeramah et al. (2013)</a> identified a de novo hemizygous c.1630G-A transition in the CLCN4 gene, resulting in a gly544-to-arg (G544R) substitution at a highly conserved residue within an intramembrane 4-residue loop that connects intramembrane helices P and Q. The mutation, which was found by whole-exome sequencing, was not present in the 1000 Genomes Project or Exome Sequencing Project databases. The patient developed refractory complex partial seizures with secondary generalization at age 4 months. He had microcephaly, delayed psychomotor development, hypotonia, and dystonia. Transfection of the mutation into HeLa cells showed that the mutant protein had normal localization to structures resembling ER membranes. However, in vitro functional expression studies in Xenopus oocytes showed that the mutation almost abolished the outwardly rectifying currents, consistent with a loss of function. The patient was 1 of 10 probands with a similar phenotype who underwent whole-exome sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23647072" 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 10-year-old Dutch boy (Family O) with a severe intellectual disability and seizure disorder, <a href="#9" class="mim-tip-reference" title="Palmer, E. E., Stuhlmann, T., Weinert, S., Haan, E., Van Esch, H., Holvoet, M., Boyle, J., Leffler, M., Raynaud, M., Moraine, C., van Bokhove, H., Kleefstra, T., and 38 others. <strong>De novo and inherited mutations in the X-linked gene CLCN4 are associated with syndromic intellectual disability and behavior and seizure disorders in males and females.</strong> Molec. Psychiat. 23: 222-230, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27550844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27550844</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27550844[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/mp.2016.135" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27550844">Palmer et al. (2018)</a> identified a G-to-C transversion (chrX:10181774G-C) in the CLCN4 gene, resulting in a gly544-to-arg substitution in the transmembrane domain. The boy was nonverbal, showed apathy and social disinhibition, and had absence and tonic clonic seizures diagnosed at age 3 that responded to lamotrigine. He had a round face, downslanting palpebral fissures, and an open mouth. His growth parameters were low, below the 2nd centile for head circumference and below the 1st centile for weight and height (-3.4 SD). He was not hypotonic in infancy. He showed progressive spasticity, an unsteady gait, tics, and stereotypies. A brain MRI at age 7 years was normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27550844" 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 4 male patients from a family (MRX49) with X-linked intellectual disability (MRXSRC; <a href="/entry/300114">300114</a>) originally reported by <a href="#1" class="mim-tip-reference" title="Claes, S., Vogels, A., Holvoet, M., Devriendt, K., Raeymaekers, P., Cassiman, J. J., Fryns, J. P. <strong>Regional localization of two genes for nonspecific X-linked mental retardation to Xp22.3-p22.2 (MRX49) and Xp11.3-p11.21 (MRX50).</strong> Am. J. Med. Genet. 73: 474-479, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9415477/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9415477</a>]" pmid="9415477">Claes et al. (1997)</a>, <a href="#5" class="mim-tip-reference" title="Hu, H., Haas, S. A., Chelly, J., Van Esch, H., Raynaud, M., de Brouwer, A. P. M., Weinert, S., Froyen, G., Frints, S. G. M., Laumonnier, F., Zemojtel, T., Love, M. I., and 72 others. <strong>X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes.</strong> Molec. Psychiat. 21: 133-148, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25644381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25644381</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25644381[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/mp.2014.193" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25644381">Hu et al. (2016)</a> identified a hemizygous 13-bp deletion (chrX.101,531,111-101,531,123del13, GRCh37) in the CLCN4 gene, resulting in a frameshift and premature termination (Asp15SerfsTer18). The mutation, which was found by X-chromosome exome sequencing, was filtered against the dbSNP (build 135), Exome Variant Server, and 1000 Genomes Project databases, as well as against 200 Danish exomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25644381+9415477" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 2 male patients from a family (MRX15) with X-linked intellectual disability (MRXSRC; <a href="/entry/300114">300114</a>) originally reported by <a href="#11" class="mim-tip-reference" title="Raynaud, M., Gendrot, C., Dessay, B., Moncla, A., Ayrault, A.-D., Moizard, M.-P., Toutain, A., Briault, S., Villard, L., Ronce, N., Moraine, C. <strong>X-linked mental retardation with neonatal hypotonia in a French family (MRX15): gene assignment to Xp11.22-Xp21.1.</strong> Am. J. Med. Genet. 64: 97-106, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8826458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8826458</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1<97::AID-AJMG17>3.0.CO;2-N" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8826458">Raynaud et al. (1996)</a>, <a href="#5" class="mim-tip-reference" title="Hu, H., Haas, S. A., Chelly, J., Van Esch, H., Raynaud, M., de Brouwer, A. P. M., Weinert, S., Froyen, G., Frints, S. G. M., Laumonnier, F., Zemojtel, T., Love, M. I., and 72 others. <strong>X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes.</strong> Molec. Psychiat. 21: 133-148, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25644381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25644381</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25644381[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/mp.2014.193" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25644381">Hu et al. (2016)</a> identified a hemizygous G-to-A transition (chrX.10,188,916G-A, GRCh37) in the CLCN4 gene, resulting in a gly731-to-arg (G731R) substitution in the cytosolic cystathionine-beta-synthase domain. The mutation, which was found by X-chromosome exome sequencing, was filtered against the dbSNP (build 135), Exome Variant Server, and 1000 Genomes Project databases, as well as against 200 Danish exomes. In vitro functional expression studies in Xenopus oocytes showed that the mutation caused a marked reduction in outwardly-rectifying CLCN4 currents compared to wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8826458+25644381" 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">rs1569226551 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1569226551;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=rs1569226551" 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=rs1569226551" 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=RCV000239527 OR RCV002518545" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000239527, RCV002518545" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000239527...</a>
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<p>In a male patient (family N70) with X-linked intellectual disability (MRXSRC; <a href="/entry/300114">300114</a>), <a href="#5" class="mim-tip-reference" title="Hu, H., Haas, S. A., Chelly, J., Van Esch, H., Raynaud, M., de Brouwer, A. P. M., Weinert, S., Froyen, G., Frints, S. G. M., Laumonnier, F., Zemojtel, T., Love, M. I., and 72 others. <strong>X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes.</strong> Molec. Psychiat. 21: 133-148, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25644381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25644381</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25644381[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/mp.2014.193" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25644381">Hu et al. (2016)</a> identified a hemizygous G-to-A transition (chrX.10,155,642G-A, GRCh37) in the CLCN4 gene, resulting in a gly78-to-ser (G78S) substitution in the transmembrane domain. The patient was deceased and had a deceased similarly affected brother, but the brother was not tested for the mutation. The mutation, which was found by X-chromosome exome sequencing, was filtered against the dbSNP (build 135), Exome Variant Server, and 1000 Genomes Project databases, as well as against 200 Danish exomes. In vitro functional expression studies in Xenopus oocytes showed that the mutation caused a marked reduction in outwardly-rectifying CLCN4 currents compared to wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25644381" 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">rs1569230006 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1569230006;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=rs1569230006" 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=rs1569230006" 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=RCV000239579" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000239579" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000239579</a>
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<p>In 2 affected males from a family (family AU27) with X-linked intellectual disability (MRXSRC; <a href="/entry/300114">300114</a>), <a href="#5" class="mim-tip-reference" title="Hu, H., Haas, S. A., Chelly, J., Van Esch, H., Raynaud, M., de Brouwer, A. P. M., Weinert, S., Froyen, G., Frints, S. G. M., Laumonnier, F., Zemojtel, T., Love, M. I., and 72 others. <strong>X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes.</strong> Molec. Psychiat. 21: 133-148, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25644381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25644381</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25644381[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/mp.2014.193" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25644381">Hu et al. (2016)</a> identified a hemizygous C-to-G transversion (chrX.10,174,503C-G, GRCh37) in the CLCN4 gene, resulting in a leu221-to-val (L221V) substitution in the transmembrane domain. The mutation, which was found by X-chromosome exome sequencing, was filtered against the dbSNP (build 135), Exome Variant Server, and 1000 Genomes Project databases, as well as against 200 Danish exomes. In vitro functional expression studies in Xenopus oocytes showed that the mutation caused a marked reduction in outwardly-rectifying CLCN4 currents compared to wildtype. There were 2 additional male patients in the family with a similar disorder, but they were not tested for the mutation. One unaffected female was confirmed to be a carrier. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25644381" 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">rs1569231897 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1569231897;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=rs1569231897" 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=rs1569231897" 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=RCV000239489" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000239489" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000239489</a>
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<p>In 2 affected males from a family with X-linked intellectual disability (MRXSRC; <a href="/entry/300114">300114</a>), <a href="#5" class="mim-tip-reference" title="Hu, H., Haas, S. A., Chelly, J., Van Esch, H., Raynaud, M., de Brouwer, A. P. M., Weinert, S., Froyen, G., Frints, S. G. M., Laumonnier, F., Zemojtel, T., Love, M. I., and 72 others. <strong>X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes.</strong> Molec. Psychiat. 21: 133-148, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25644381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25644381</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25644381[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/mp.2014.193" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25644381">Hu et al. (2016)</a> identified a hemizygous G-to-A transition (chrX.10,181,750G-A, GRCh37) in the CLCN4 gene, resulting in a val536-to-met (V536M) substitution in the transmembrane domain. The mutation, which was found by X-chromosome exome sequencing, was filtered against the dbSNP (build 135), Exome Variant Server, and 1000 Genomes Project databases, as well as against 200 Danish exomes. In vitro functional expression studies in Xenopus oocytes showed that the mutation caused a marked reduction in outwardly-rectifying CLCN4 currents compared to wildtype. There were 5 additional male patients and 1 female in the family with a similar disorder, but they were not tested for the mutation. One unaffected female was confirmed to be a carrier. (In the article by <a href="#5" class="mim-tip-reference" title="Hu, H., Haas, S. A., Chelly, J., Van Esch, H., Raynaud, M., de Brouwer, A. P. M., Weinert, S., Froyen, G., Frints, S. G. M., Laumonnier, F., Zemojtel, T., Love, M. I., and 72 others. <strong>X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes.</strong> Molec. Psychiat. 21: 133-148, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25644381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25644381</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25644381[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/mp.2014.193" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25644381">Hu et al. (2016)</a>, this family was designated family AU4 in figure 1 and supplement table 7, but as family AU9 in table 2.) <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25644381" 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">rs879255584 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs879255584;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=rs879255584" 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=rs879255584" 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=RCV000239734 OR RCV000721130 OR RCV000816910 OR RCV002252041" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000239734, RCV000721130, RCV000816910, RCV002252041" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000239734...</a>
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<p>In a 15-year-old Scottish girl (Family M) with severe intellectual disability and a history of brief absence seizures (MRXSRC; <a href="/entry/300114">300114</a>), <a href="#9" class="mim-tip-reference" title="Palmer, E. E., Stuhlmann, T., Weinert, S., Haan, E., Van Esch, H., Holvoet, M., Boyle, J., Leffler, M., Raynaud, M., Moraine, C., van Bokhove, H., Kleefstra, T., and 38 others. <strong>De novo and inherited mutations in the X-linked gene CLCN4 are associated with syndromic intellectual disability and behavior and seizure disorders in males and females.</strong> Molec. Psychiat. 23: 222-230, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27550844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27550844</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27550844[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/mp.2016.135" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27550844">Palmer et al. (2018)</a> identified a de novo C-to-T transition (chrX:10188877C-T) in the CLCN4 gene, resulting in an arg718-to-trp (R718W) substitution within the second cytosolic cystathionine-beta-synthase domain. The patient was nonverbal, drooled, and exhibited self-abusive behavior. No X-inactivation studies were performed. Expression of the variant in Xenopus oocytes showed reduced steady-state current compared to wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27550844" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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|
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|
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<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Claes1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Claes, S., Vogels, A., Holvoet, M., Devriendt, K., Raeymaekers, P., Cassiman, J. J., Fryns, J. P.
|
|
<strong>Regional localization of two genes for nonspecific X-linked mental retardation to Xp22.3-p22.2 (MRX49) and Xp11.3-p11.21 (MRX50).</strong>
|
|
Am. J. Med. Genet. 73: 474-479, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9415477/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9415477</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9415477" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Disteche1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Disteche, C. M., Brannan, C. I., Larsen, A., Adler, D. A., Schorderet, D. F., Gearing, D., Copeland, N. G., Jenkins, N. A., Park, L. S.
|
|
<strong>The human pseudoautosomal GM-CSF receptor alpha subunit gene is autosomal in mouse.</strong>
|
|
Nature Genet. 1: 333-336, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1363815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1363815</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1363815" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0892-333" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Ellis1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ellis, N. A.
|
|
<strong>Ecce Ohno.</strong>
|
|
Nature Genet. 10: 373-375, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670482/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670482</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7670482" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0895-373" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Haldane1922" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Haldane, J. B. S.
|
|
<strong>Sex ratio and unisexual sterility in hybrid animals.</strong>
|
|
J. Genet. 12: 101-109, 1922.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Hu2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hu, H., Haas, S. A., Chelly, J., Van Esch, H., Raynaud, M., de Brouwer, A. P. M., Weinert, S., Froyen, G., Frints, S. G. M., Laumonnier, F., Zemojtel, T., Love, M. I., and 72 others.
|
|
<strong>X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes.</strong>
|
|
Molec. Psychiat. 21: 133-148, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25644381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25644381</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25644381[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25644381" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/mp.2014.193" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Milatovich1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Milatovich, A., Kitamura, T., Miyajima, A., Francke, U.
|
|
<strong>Gene for the alpha-subunit of the human interleukin-3 receptor (IL3RA) localized to the X-Y pseudoautosomal region.</strong>
|
|
Am. J. Hum. Genet. 53: 1146-1153, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8213838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8213838</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8213838" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Nguyen2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nguyen, D. K., Yang, F., Kaul, R., Alkan, C., Antonellis, A., Friery, K. F., Zhu, B., de Jong, P. J., Disteche, C. M.
|
|
<strong>Clcn4-2 genomic structure differs between the X locus in Mus spretus and the autosomal locus in Mus musculus: AT motif enrichment on the X.</strong>
|
|
Genome Res. 21: 402-409, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21282478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21282478</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21282478[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21282478" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1101/gr.108563.110" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Ohno1967" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ohno, S.
|
|
<strong>Sex Chromosomes and Sex-linked Genes.</strong>
|
|
Berlin and New York: Springer (pub.) 1967.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Palmer2018" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Palmer, E. E., Stuhlmann, T., Weinert, S., Haan, E., Van Esch, H., Holvoet, M., Boyle, J., Leffler, M., Raynaud, M., Moraine, C., van Bokhove, H., Kleefstra, T., and 38 others.
|
|
<strong>De novo and inherited mutations in the X-linked gene CLCN4 are associated with syndromic intellectual disability and behavior and seizure disorders in males and females.</strong>
|
|
Molec. Psychiat. 23: 222-230, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27550844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27550844</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27550844[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27550844" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/mp.2016.135" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Palmer1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Palmer, S., Perry, J., Ashworth, A.
|
|
<strong>A contravention of Ohno's law in mice.</strong>
|
|
Nature Genet. 10: 472-476, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670497/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670497</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7670497" 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/ng0895-472" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Raynaud1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Raynaud, M., Gendrot, C., Dessay, B., Moncla, A., Ayrault, A.-D., Moizard, M.-P., Toutain, A., Briault, S., Villard, L., Ronce, N., Moraine, C.
|
|
<strong>X-linked mental retardation with neonatal hypotonia in a French family (MRX15): gene assignment to Xp11.22-Xp21.1.</strong>
|
|
Am. J. Med. Genet. 64: 97-106, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8826458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8826458</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8826458" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1<97::AID-AJMG17>3.0.CO;2-N" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Rugarli1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rugarli, E. I., Adler, D. A., Borsani, G., Tsuchiya, K., Franco, B., Hauge, X., Disteche, C., Chapman, V., Ballabio, A.
|
|
<strong>Different chromosomal localization of the Clcn4 gene in Mus spretus and C57BL/6J mice.</strong>
|
|
Nature Genet. 10: 466-471, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670496/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670496</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7670496" 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/ng0895-466" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Schnur1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schnur, R. E., Wick, P. A.
|
|
<strong>Intragenic TaqI restriction fragment length polymorphism (RFLP) in CLCN4, between the loci for X-linked ocular albinism (OA1) and microphthalmia with linear skin defects syndrome (MLS).</strong>
|
|
Hum. Genet. 95: 594-595, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7759088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7759088</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7759088" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
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|
|
|
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[<a href="https://doi.org/10.1007/BF00223880" target="_blank">Full Text</a>]
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|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="van Slegtenhorst1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
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|
|
van Slegtenhorst, M. A., Bassi, M. T., Borsani, G., Wapenaar, M. C., Ferrero, G. B., de Conciliis, L., Rugarli, E. I., Grillo, A., Franco, B., Zoghbi, H. Y., Ballabio, A.
|
|
<strong>A gene from the Xp22.3 region shares homology with voltage-gated chloride channels.</strong>
|
|
Hum. Molec. Genet. 3: 547-552, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8069296/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8069296</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8069296" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1093/hmg/3.4.547" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
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<a id="Veeramah2013" class="mim-anchor"></a>
|
|
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|
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|
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Veeramah, K. R., Johnstone, L., Karafet, T. M., Wolf, D., Sprissler, R., Salogiannis, J., Barth-Maron, A., Greenberg, M. E., Stuhlmann, T., Weinert, S., Jentsch, T. J., Pazzi, M., Restifo, L. L., Talwar, D., Erickson, R. P., Hammer, M. F.
|
|
<strong>Exome sequencing reveals new causal mutations in children with epileptic encephalopathies.</strong>
|
|
Epilepsia 54: 1270-1281, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23647072/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23647072</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23647072[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23647072" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/epi.12201" target="_blank">Full Text</a>]
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|
|
|
|
|
</p>
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Matthew B. Gross - updated : 10/17/2024
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<span class="mim-text-font">
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Joanna S. Amberger - updated : 11/07/2018<br>Cassandra L. Kniffin - updated : 08/02/2016<br>Cassandra L. Kniffin - updated : 2/25/2014
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Creation Date:
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<span class="mim-text-font">
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Victor A. McKusick : 6/21/1994
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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mgross : 10/17/2024
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 11/07/2018<br>carol : 08/03/2016<br>ckniffin : 08/02/2016<br>carol : 02/26/2014<br>mcolton : 2/25/2014<br>ckniffin : 2/25/2014<br>mgross : 9/11/2012<br>carol : 10/31/2008<br>carol : 4/30/2002<br>carol : 9/16/1999<br>mark : 8/12/1997<br>mark : 7/8/1997<br>mark : 7/7/1996<br>carol : 6/22/1996<br>mark : 11/14/1995<br>terry : 6/15/1995<br>jason : 6/21/1994
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<span class="mim-font">
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<strong>*</strong> 302910
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</h3>
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<h3>
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CHLORIDE CHANNEL 4; CLCN4
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</h3>
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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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<h4>
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<span class="mim-font">
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CHLORIDE CHANNEL, VOLTAGE-GATED, 4
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</h4>
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</div>
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<br />
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: CLCN4</em></strong>
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</span>
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</p>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 1172691004;
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</p>
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<strong>
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<em>
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Cytogenetic location: Xp22.2
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Genomic coordinates <span class="small">(GRCh38)</span> : X:10,156,975-10,237,660 </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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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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Phenotype <br /> mapping key
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<tbody>
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<td rowspan="1">
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<span class="mim-font">
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Xp22.2
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<span class="mim-font">
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Raynaud-Claes syndrome
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</td>
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<span class="mim-font">
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300114
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<span class="mim-font">
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X-linked dominant
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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 class="mim-font">
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<strong>TEXT</strong>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>CLCN4 is a voltage-gated chloride channel (van Slegtenhorst et al., 1994). </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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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</h4>
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<span class="mim-text-font">
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<p>In the course of constructing a comprehensive transcript map of the Xp22.3 region, van Slegtenhorst et al. (1994) identified an evolutionarily conserved CpG island and cloned the corresponding gene. The predicted 760-amino acid protein contained 12 hydrophobic domains and shared sequence and structural similarities with all the previously isolated members of the family of voltage-gated chloride channels. In contrast with most genes isolated from the Xp22.3 region, CLCN4 did not share homology with the Y chromosome, but was conserved in mouse and hamster. Expression studies demonstrated a 7.5-kb transcript that is particularly abundant in skeletal muscle and also detectable in brain and heart. Thus, this gene encodes a newly identified voltage-gated chloride channel. </p>
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</span>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Nguyen et al. (2011) compared the CLCN4 exon/intron structure of 8 mammalian species. In all species examined, the ATG translation start site was located at the beginning of exon 3, and the poly(A) tail was within exon 13. The coding sequence of exons 3 to 13 was highly conserved, with an overall 80 to 90% identity between species. </p>
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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>The CLCN4 gene maps to chromosome Xp22.3 (van Slegtenhorst et al., 1994). </p><p>Rugarli et al. (1995) found that in the wild Mediterranean mouse Mus spretus, the Cln4 gene maps to the X chromosome as it does in the human; however, in the inbred strain of laboratory mouse C57BL/6J, they found that it maps to chromosome 7. Findings indicated that a recent evolutionary rearrangement occurred in the mouse sex chromosomes very close to the pseudoautosomal region (PAR). The data were considered molecular evidence for a major divergence near the pseudoautosomal region consistent with the hypothesis that hybrid sterility in these species results from abnormal pairing of sex chromosomes during male meiosis. They found that Cln4 is the closest cloned gene to the M. spretus pseudoautosomal region and the most distal locus displaying a conserved position between the human and this mouse locus. The X-inactivation status of the locus in M. spretus was demonstrated by the finding that in F1 females from a cross between M. spretus and an inbred-derived mouse carrying the t(X;16)16H balanced translocation, it was always the normal M. spretus X chromosome that was inactive in adult tissues. This completely skewed X inactivation provided a system for assaying expression of genes from the inactive X chromosome once the parental alleles could be distinguished. </p><p>Palmer et al. (1995) likewise found what they referred to as 'contravention of Ohno's law' in the course of mapping a cDNA mouse Cln4 in an interspecific backcross. This was the first example of a gene unique to the X chromosome in 1 eutherian species but autosomal in another. The consequence of this chromosomal rearrangement was that the gene was lost by mendelian segregation in a subset of the male progeny of a (C57BL/6 x Mus spretus) x Mus spretus backcross. </p>
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</span>
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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>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In a 14-month-old boy with Raynaud-Claes syndrome (MRXSRC; 300114) who presented with epileptic encephalopathy, Veeramah et al. (2013) identified a de novo hemizygous missense mutation in the CLCN4 gene (G544R; 302910.0001). The mutation was found by whole-exome sequencing. In vitro functional expression studies in Xenopus oocytes showed that the mutation almost abolished the outwardly rectifying currents, consistent with a loss of function. The patient was 1 of 10 probands with a similar phenotype who underwent whole-exome sequencing. </p><p>In affected male members of 5 unrelated families with X-linked intellectual disability, including the family (MRX49) reported by Claes et al. (1997) and the family (MRX15) reported by Raynaud et al. (1996), Hu et al. (2016) identified hemizygous mutations in the CLCN4 gene (302910.0002-302910.0006). The mutations were found by X-chromosome exome sequencing. One of the mutations resulted in a truncated protein, whereas the 4 others were missense mutations. In vitro functional expression studies in Xenopus oocytes showed that all of the missense mutations caused a marked reduction in outwardly-rectifying CLCN4 currents compared to wildtype. Knockdown of the Clcn4 gene in mouse hippocampal neurons resulted in 30% less dendritic branches compared to controls, and primary neurons derived from Clcn4-null mice showed similar, but more subtle, changes. The findings were consistent with a loss of function underlying the cognitive defects in these families. </p><p>Palmer et al. (2018) summarized phenotypic and molecular genetic information on 52 individuals from 16 families with a syndromic intellectual disability disorder, including 6 previously reported families, and mutation in the CLCN4 gene. In 5 affected females (see, e.g., 302910.0007) and 2 affected males, the mutations occurred de novo. The mutation spectrum included frameshift, missense, and splice site variants, and one single-exon deletion. </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>In his classic monograph entitled 'Sex Chromosomes and Sex-Linked Genes,' Ohno (1967) promulgated his famous law based on numerous examples of conservation of X-linked genes, cementing the concept of the X chromosome in placental mammals as an immutable element (Ellis, 1995). Motivating most of Ohno's thesis was the compelling but complex evolutionary argument that heteromorphic sex chromosomes in mammals evolved originally from a pair of homomorphic autosomes. Mutations occurred in 2 (or more) genes on 1 of these chromosomes (the proto-Y chromosome) but caused the genes to become factors in the sexual differentiation of the male. These genes had to segregate together; thus, recombination was suppressed between the incipient sex chromosomes. As a consequence of recombination suppression, the proto-Y chromosome suffered gradual genetic deterioration that eventually left it a 'dummy chromosome.' At the same time, a dosage compensation mechanism evolved that doubled the rate of product output of X-linked genes (because monosomy is deleterious) and led to the inactivation of the extra X chromosome in females. The X-chromosome inactivation mechanism became an evolutionary barrier to the shuffling of genes between the X and autosomes because, as had previously been shown, such rearrangements disrupt the compensation mechanism. Laxity in Ohno's law was previously discovered in relation to the pseudoautosomal region in which DNA segments of the X and Y pair and show crossing-over, generally presumed to be necessary for the proper segregation of the X and Y chromosomes. Genes in the PAR escape X inactivation which removes them from the evolutionary force that would retain them on the X chromosome. The genes that are known to be in the PAR include ASMT (300015) and ASMTY (402500); the first such gene to be discovered, MIC2 (313470) and MIC2Y (450000); the XG blood group gene (300879 and XGPY); IL3RA (308385) and IL3RAY (430000); AMELX (300391) and AMELY (410000); CSF2RA (306250) and CSF2RY (425000); and ANT3 (300151) and ANT3Y (403000). Consistent with this laxity, syntenic conservation of genes in the PAR is not a hard and fast rule. For example, CSF2RA and IL3RA are pseudoautosomal in the human and autosomal in the mouse; see Disteche et al. (1992) and Milatovich et al. (1993), respectively. A further wrinkle on the evolution of this region of the X chromosome is demonstrated by the steroid sulfatase gene (STS; 300747), which escapes X inactivation in both humans and the mouse but is X-linked in humans while pseudoautosomal in the mouse. The PAR has been implicated in the mouse and perhaps in other species in providing an explanation for Haldane's rule (Haldane, 1922) that in interspecific hybrids, the heterogametic sex of the F1 offspring is absent, rare, or sterile. In crosses between M. spretus and M. musculus, the male F1 offspring are sterile. Their testes are small, probably due to breakdown of spermatogenesis after meiosis 1. Almost all X-Y bivalents dissociate by diakinesis, probably because of the failure of the sex chromosomes from the 2 different species to pair and recombine properly. Lack of homology between the PARs may be the underlying cause. </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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<h4>
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<span class="mim-font">
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<strong>History</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>Schnur and Wick (1995) detected a TaqI RFLP within the CLCN4 gene which lies between the loci for ocular albinism (OA1; 300500) and microphthalmia with linear skin defects (MLS; 309801). No recombination was observed between the RFLP and the OA1 mutation in 3 informative families, indicating that the marker would be useful for genetic counseling in OA1. </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>ALLELIC VARIANTS</strong>
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</span>
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<strong>7 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 RAYNAUD-CLAES SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CLCN4, GLY544ARG
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<br />
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SNP: rs587777161,
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ClinVar: RCV000087143, RCV000520512
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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 14-month-old boy with Raynaud-Claes syndrome (MRXSRC; 300114) who presented with epileptic encephalopathy, Veeramah et al. (2013) identified a de novo hemizygous c.1630G-A transition in the CLCN4 gene, resulting in a gly544-to-arg (G544R) substitution at a highly conserved residue within an intramembrane 4-residue loop that connects intramembrane helices P and Q. The mutation, which was found by whole-exome sequencing, was not present in the 1000 Genomes Project or Exome Sequencing Project databases. The patient developed refractory complex partial seizures with secondary generalization at age 4 months. He had microcephaly, delayed psychomotor development, hypotonia, and dystonia. Transfection of the mutation into HeLa cells showed that the mutant protein had normal localization to structures resembling ER membranes. However, in vitro functional expression studies in Xenopus oocytes showed that the mutation almost abolished the outwardly rectifying currents, consistent with a loss of function. The patient was 1 of 10 probands with a similar phenotype who underwent whole-exome sequencing. </p><p>In a 10-year-old Dutch boy (Family O) with a severe intellectual disability and seizure disorder, Palmer et al. (2018) identified a G-to-C transversion (chrX:10181774G-C) in the CLCN4 gene, resulting in a gly544-to-arg substitution in the transmembrane domain. The boy was nonverbal, showed apathy and social disinhibition, and had absence and tonic clonic seizures diagnosed at age 3 that responded to lamotrigine. He had a round face, downslanting palpebral fissures, and an open mouth. His growth parameters were low, below the 2nd centile for head circumference and below the 1st centile for weight and height (-3.4 SD). He was not hypotonic in infancy. He showed progressive spasticity, an unsteady gait, tics, and stereotypies. A brain MRI at age 7 years was normal. </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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<h4>
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<span class="mim-font">
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<strong>.0002 RAYNAUD-CLAES SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CLCN4, 13-BP DEL
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<br />
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SNP: rs1923775114,
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ClinVar: RCV000239554
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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 4 male patients from a family (MRX49) with X-linked intellectual disability (MRXSRC; 300114) originally reported by Claes et al. (1997), Hu et al. (2016) identified a hemizygous 13-bp deletion (chrX.101,531,111-101,531,123del13, GRCh37) in the CLCN4 gene, resulting in a frameshift and premature termination (Asp15SerfsTer18). The mutation, which was found by X-chromosome exome sequencing, was filtered against the dbSNP (build 135), Exome Variant Server, and 1000 Genomes Project databases, as well as against 200 Danish exomes. </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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<h4>
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<span class="mim-font">
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<strong>.0003 RAYNAUD-CLAES SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CLCN4, GLY731ARG
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<br />
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SNP: rs1569233549,
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ClinVar: RCV000239467
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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 male patients from a family (MRX15) with X-linked intellectual disability (MRXSRC; 300114) originally reported by Raynaud et al. (1996), Hu et al. (2016) identified a hemizygous G-to-A transition (chrX.10,188,916G-A, GRCh37) in the CLCN4 gene, resulting in a gly731-to-arg (G731R) substitution in the cytosolic cystathionine-beta-synthase domain. The mutation, which was found by X-chromosome exome sequencing, was filtered against the dbSNP (build 135), Exome Variant Server, and 1000 Genomes Project databases, as well as against 200 Danish exomes. In vitro functional expression studies in Xenopus oocytes showed that the mutation caused a marked reduction in outwardly-rectifying CLCN4 currents compared to wildtype. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 RAYNAUD-CLAES SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CLCN4, GLY78SER
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<br />
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SNP: rs1569226551,
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ClinVar: RCV000239527, RCV002518545
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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 male patient (family N70) with X-linked intellectual disability (MRXSRC; 300114), Hu et al. (2016) identified a hemizygous G-to-A transition (chrX.10,155,642G-A, GRCh37) in the CLCN4 gene, resulting in a gly78-to-ser (G78S) substitution in the transmembrane domain. The patient was deceased and had a deceased similarly affected brother, but the brother was not tested for the mutation. The mutation, which was found by X-chromosome exome sequencing, was filtered against the dbSNP (build 135), Exome Variant Server, and 1000 Genomes Project databases, as well as against 200 Danish exomes. In vitro functional expression studies in Xenopus oocytes showed that the mutation caused a marked reduction in outwardly-rectifying CLCN4 currents compared to wildtype. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 RAYNAUD-CLAES SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CLCN4, LEU221VAL
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<br />
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SNP: rs1569230006,
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ClinVar: RCV000239579
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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 males from a family (family AU27) with X-linked intellectual disability (MRXSRC; 300114), Hu et al. (2016) identified a hemizygous C-to-G transversion (chrX.10,174,503C-G, GRCh37) in the CLCN4 gene, resulting in a leu221-to-val (L221V) substitution in the transmembrane domain. The mutation, which was found by X-chromosome exome sequencing, was filtered against the dbSNP (build 135), Exome Variant Server, and 1000 Genomes Project databases, as well as against 200 Danish exomes. In vitro functional expression studies in Xenopus oocytes showed that the mutation caused a marked reduction in outwardly-rectifying CLCN4 currents compared to wildtype. There were 2 additional male patients in the family with a similar disorder, but they were not tested for the mutation. One unaffected female was confirmed to be a carrier. </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>.0006 RAYNAUD-CLAES SYNDROME</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CLCN4, VAL536MET
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<br />
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SNP: rs1569231897,
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ClinVar: RCV000239489
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In 2 affected males from a family with X-linked intellectual disability (MRXSRC; 300114), Hu et al. (2016) identified a hemizygous G-to-A transition (chrX.10,181,750G-A, GRCh37) in the CLCN4 gene, resulting in a val536-to-met (V536M) substitution in the transmembrane domain. The mutation, which was found by X-chromosome exome sequencing, was filtered against the dbSNP (build 135), Exome Variant Server, and 1000 Genomes Project databases, as well as against 200 Danish exomes. In vitro functional expression studies in Xenopus oocytes showed that the mutation caused a marked reduction in outwardly-rectifying CLCN4 currents compared to wildtype. There were 5 additional male patients and 1 female in the family with a similar disorder, but they were not tested for the mutation. One unaffected female was confirmed to be a carrier. (In the article by Hu et al. (2016), this family was designated family AU4 in figure 1 and supplement table 7, but as family AU9 in table 2.) </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 RAYNAUD-CLAES SYNDROME</strong>
|
|
</span>
|
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CLCN4, ARG718TRP
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<br />
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SNP: rs879255584,
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ClinVar: RCV000239734, RCV000721130, RCV000816910, RCV002252041
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a 15-year-old Scottish girl (Family M) with severe intellectual disability and a history of brief absence seizures (MRXSRC; 300114), Palmer et al. (2018) identified a de novo C-to-T transition (chrX:10188877C-T) in the CLCN4 gene, resulting in an arg718-to-trp (R718W) substitution within the second cytosolic cystathionine-beta-synthase domain. The patient was nonverbal, drooled, and exhibited self-abusive behavior. No X-inactivation studies were performed. Expression of the variant in Xenopus oocytes showed reduced steady-state current compared to wildtype. </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>REFERENCES</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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<ol>
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<li>
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|
<p class="mim-text-font">
|
|
Claes, S., Vogels, A., Holvoet, M., Devriendt, K., Raeymaekers, P., Cassiman, J. J., Fryns, J. P.
|
|
<strong>Regional localization of two genes for nonspecific X-linked mental retardation to Xp22.3-p22.2 (MRX49) and Xp11.3-p11.21 (MRX50).</strong>
|
|
Am. J. Med. Genet. 73: 474-479, 1997.
|
|
|
|
|
|
[PubMed: 9415477]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Disteche, C. M., Brannan, C. I., Larsen, A., Adler, D. A., Schorderet, D. F., Gearing, D., Copeland, N. G., Jenkins, N. A., Park, L. S.
|
|
<strong>The human pseudoautosomal GM-CSF receptor alpha subunit gene is autosomal in mouse.</strong>
|
|
Nature Genet. 1: 333-336, 1992.
|
|
|
|
|
|
[PubMed: 1363815]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0892-333]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ellis, N. A.
|
|
<strong>Ecce Ohno.</strong>
|
|
Nature Genet. 10: 373-375, 1995.
|
|
|
|
|
|
[PubMed: 7670482]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0895-373]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
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<p class="mim-text-font">
|
|
Haldane, J. B. S.
|
|
<strong>Sex ratio and unisexual sterility in hybrid animals.</strong>
|
|
J. Genet. 12: 101-109, 1922.
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hu, H., Haas, S. A., Chelly, J., Van Esch, H., Raynaud, M., de Brouwer, A. P. M., Weinert, S., Froyen, G., Frints, S. G. M., Laumonnier, F., Zemojtel, T., Love, M. I., and 72 others.
|
|
<strong>X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes.</strong>
|
|
Molec. Psychiat. 21: 133-148, 2016.
|
|
|
|
|
|
[PubMed: 25644381]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/mp.2014.193]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Milatovich, A., Kitamura, T., Miyajima, A., Francke, U.
|
|
<strong>Gene for the alpha-subunit of the human interleukin-3 receptor (IL3RA) localized to the X-Y pseudoautosomal region.</strong>
|
|
Am. J. Hum. Genet. 53: 1146-1153, 1993.
|
|
|
|
|
|
[PubMed: 8213838]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nguyen, D. K., Yang, F., Kaul, R., Alkan, C., Antonellis, A., Friery, K. F., Zhu, B., de Jong, P. J., Disteche, C. M.
|
|
<strong>Clcn4-2 genomic structure differs between the X locus in Mus spretus and the autosomal locus in Mus musculus: AT motif enrichment on the X.</strong>
|
|
Genome Res. 21: 402-409, 2011.
|
|
|
|
|
|
[PubMed: 21282478]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1101/gr.108563.110]
|
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</p>
|
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</li>
|
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
Ohno, S.
|
|
<strong>Sex Chromosomes and Sex-linked Genes.</strong>
|
|
Berlin and New York: Springer (pub.) 1967.
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Palmer, E. E., Stuhlmann, T., Weinert, S., Haan, E., Van Esch, H., Holvoet, M., Boyle, J., Leffler, M., Raynaud, M., Moraine, C., van Bokhove, H., Kleefstra, T., and 38 others.
|
|
<strong>De novo and inherited mutations in the X-linked gene CLCN4 are associated with syndromic intellectual disability and behavior and seizure disorders in males and females.</strong>
|
|
Molec. Psychiat. 23: 222-230, 2018.
|
|
|
|
|
|
[PubMed: 27550844]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/mp.2016.135]
|
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|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Palmer, S., Perry, J., Ashworth, A.
|
|
<strong>A contravention of Ohno's law in mice.</strong>
|
|
Nature Genet. 10: 472-476, 1995.
|
|
|
|
|
|
[PubMed: 7670497]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0895-472]
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</p>
|
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</li>
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|
|
|
<li>
|
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<p class="mim-text-font">
|
|
Raynaud, M., Gendrot, C., Dessay, B., Moncla, A., Ayrault, A.-D., Moizard, M.-P., Toutain, A., Briault, S., Villard, L., Ronce, N., Moraine, C.
|
|
<strong>X-linked mental retardation with neonatal hypotonia in a French family (MRX15): gene assignment to Xp11.22-Xp21.1.</strong>
|
|
Am. J. Med. Genet. 64: 97-106, 1996.
|
|
|
|
|
|
[PubMed: 8826458]
|
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|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1<97::AID-AJMG17>3.0.CO;2-N]
|
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|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rugarli, E. I., Adler, D. A., Borsani, G., Tsuchiya, K., Franco, B., Hauge, X., Disteche, C., Chapman, V., Ballabio, A.
|
|
<strong>Different chromosomal localization of the Clcn4 gene in Mus spretus and C57BL/6J mice.</strong>
|
|
Nature Genet. 10: 466-471, 1995.
|
|
|
|
|
|
[PubMed: 7670496]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0895-466]
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
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<p class="mim-text-font">
|
|
Schnur, R. E., Wick, P. A.
|
|
<strong>Intragenic TaqI restriction fragment length polymorphism (RFLP) in CLCN4, between the loci for X-linked ocular albinism (OA1) and microphthalmia with linear skin defects syndrome (MLS).</strong>
|
|
Hum. Genet. 95: 594-595, 1995.
|
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|
|
[PubMed: 7759088]
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[Full Text: https://doi.org/10.1007/BF00223880]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
van Slegtenhorst, M. A., Bassi, M. T., Borsani, G., Wapenaar, M. C., Ferrero, G. B., de Conciliis, L., Rugarli, E. I., Grillo, A., Franco, B., Zoghbi, H. Y., Ballabio, A.
|
|
<strong>A gene from the Xp22.3 region shares homology with voltage-gated chloride channels.</strong>
|
|
Hum. Molec. Genet. 3: 547-552, 1994.
|
|
|
|
|
|
[PubMed: 8069296]
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|
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|
|
[Full Text: https://doi.org/10.1093/hmg/3.4.547]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Veeramah, K. R., Johnstone, L., Karafet, T. M., Wolf, D., Sprissler, R., Salogiannis, J., Barth-Maron, A., Greenberg, M. E., Stuhlmann, T., Weinert, S., Jentsch, T. J., Pazzi, M., Restifo, L. L., Talwar, D., Erickson, R. P., Hammer, M. F.
|
|
<strong>Exome sequencing reveals new causal mutations in children with epileptic encephalopathies.</strong>
|
|
Epilepsia 54: 1270-1281, 2013.
|
|
|
|
|
|
[PubMed: 23647072]
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|
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|
|
[Full Text: https://doi.org/10.1111/epi.12201]
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</p>
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</li>
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</ol>
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<div>
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<br />
|
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</div>
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</div>
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</div>
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<div>
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<div class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
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<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Matthew B. Gross - updated : 10/17/2024<br>Joanna S. Amberger - updated : 11/07/2018<br>Cassandra L. Kniffin - updated : 08/02/2016<br>Cassandra L. Kniffin - updated : 2/25/2014
|
|
</span>
|
|
</div>
|
|
</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 class="row">
|
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
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<span class="text-nowrap mim-text-font">
|
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Creation Date:
|
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</span>
|
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</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/21/1994
|
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</span>
|
|
</div>
|
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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 class="row">
|
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
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<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
mgross : 10/17/2024<br>carol : 11/07/2018<br>carol : 08/03/2016<br>ckniffin : 08/02/2016<br>carol : 02/26/2014<br>mcolton : 2/25/2014<br>ckniffin : 2/25/2014<br>mgross : 9/11/2012<br>carol : 10/31/2008<br>carol : 4/30/2002<br>carol : 9/16/1999<br>mark : 8/12/1997<br>mark : 7/8/1997<br>mark : 7/7/1996<br>carol : 6/22/1996<br>mark : 11/14/1995<br>terry : 6/15/1995<br>jason : 6/21/1994
|
|
</span>
|
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</div>
|
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</div>
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</div>
|
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<div>
|
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<br />
|
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