3873 lines
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- *604418 - GAP JUNCTION PROTEIN, BETA-6; GJB6
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- OMIM
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<p>
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<span class="h4">*604418</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<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/604418">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<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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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000121742;t=ENST00000647029" 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=10804" 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=604418" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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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=ENSG00000121742;t=ENST00000647029" 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_001110219,NM_001110220,NM_001110221,NM_001370090,NM_001370091,NM_001370092,NM_006783,XM_047430056,XM_047430057" 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_001110219" 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=604418" 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=05107&isoform_id=05107_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/GJB6" 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/4127986,24660317,31580773,34978349,40254837,45503288,55925661,55925663,55925665,119628659,119628660,119628661,119628662,119628663,158260207,158966714,158966717,159032020,193786771,1625627209,1625627211,1625627213,2217293464,2217293466,2462536057,2462536059" 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/O95452" 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=10804" 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=ENSG00000121742;t=ENST00000647029" 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=GJB6" 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=GJB6" 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+10804" 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/GJB6" 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:10804" 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/10804" 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=chr13&hgg_gene=ENST00000647029.1&hgg_start=20221962&hgg_end=20232319&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 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:4288" 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:4288" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/gjb6" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=604418[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=604418[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://gnomad.broadinstitute.org/gene/ENSG00000121742" 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=GJB6" 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=GJB6" 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="#mimLocusSpecificDBsFold" id="mimLocusSpecificDBsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A gene-specific database of variation."><span id="mimLocusSpecificDBsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Locus Specific DBs</div>
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<div id="mimLocusSpecificDBsFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="http://davinci.crg.es/deafness/" title="The Connexin-deafness homepage" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">The Connexin-deafness home…</a></div><div style="margin-left: 0.5em;"><a href="http://hereditaryhearingloss.org/" title="Hereditary Hearing Loss Homepage" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Hereditary Hearing Loss Ho…</a></div><div style="margin-left: 0.5em;"><a href="https://research.cchmc.org/LOVD2/home.php?select_db=GJB6" title="CCHMC - Human Genetics Mutation Database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">CCHMC - Human Genetics Mut…</a></div>
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</div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=GJB6&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/PA28699" 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:4288" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:107588" 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/GJB6#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:107588" 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/10804/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=10804" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-040406-1" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=GJB6&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> 54209007<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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604418
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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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GAP JUNCTION PROTEIN, BETA-6; GJB6
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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CONNEXIN 30; CX30
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=GJB6" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">GJB6</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>
|
|
Cytogenetic location: <a href="/geneMap/13/16?start=-3&limit=10&highlight=16">13q12.11</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr13:20221962-20232319&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'})">13:20,221,962-20,232,319</a> </span>
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</em>
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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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>
|
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Location
|
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</th>
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<th>
|
|
Phenotype
|
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<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=612643,612645,220290,129500" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
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</a>
|
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</span>
|
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</th>
|
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<th>
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|
Phenotype <br /> MIM number
|
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</th>
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<th>
|
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Inheritance
|
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</th>
|
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<th>
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Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
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</thead>
|
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<tbody>
|
|
|
|
<tr>
|
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<td rowspan="4">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/13/16?start=-3&limit=10&highlight=16">
|
|
13q12.11
|
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</a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Deafness, autosomal dominant 3B
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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|
<a href="/entry/612643"> 612643 </a>
|
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
|
|
Deafness, autosomal recessive 1B
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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|
<a href="/entry/612645"> 612645 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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|
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</span>
|
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</td>
|
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</tr>
|
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|
|
|
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
Deafness, digenic GJB2/GJB6
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<p>The connexin gene family codes for the protein subunits of gap junction channels that mediate direct diffusion of ions and metabolites between the cytoplasm of adjacent cells. Connexins span the plasma membrane 4 times, with amino- and carboxy-terminal regions facing the cytoplasm. Connexin genes are expressed in a cell type-specific manner with overlapping specificity. The gap junction channels have unique properties depending on the type of connexins constituting the channel. Connexin-30 (GJB6) is a gap junction subunit expressed abundantly in brain and cochlea (summary by <a href="#2" class="mim-tip-reference" title="Dahl, E., Manthey, D., Chen, Y., Schwarz, H. J., Chang, Y. S., Lalley, P. A., Nicholson, B. J., Willecke, K. <strong>Molecular cloning and functional expression of mouse connexin-30, a gap junction gene highly expressed in adult brain and skin.</strong> J. Biol. Chem. 271: 17903-17910, 1996. Note: Erratum: J. Biol. Chem. 271: 26444 only, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8663509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8663509</a>] [<a href="https://doi.org/10.1074/jbc.271.30.17903" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8663509">Dahl et al., 1996</a>; <a href="#13" class="mim-tip-reference" title="Lautermann, J., ten Cate, W.-J., Altenhoff, P., Grummer, R., Traub, O., Frank, H.-G., Jahnke, K., Winterhager, E. <strong>Expression of the gap-junction connexins 26 and 30 in the rat cochlea.</strong> Cell Tissue Res. 294: 415-420, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9799458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9799458</a>] [<a href="https://doi.org/10.1007/s004410051192" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9799458">Lautermann et al., 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9799458+8663509" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#2" class="mim-tip-reference" title="Dahl, E., Manthey, D., Chen, Y., Schwarz, H. J., Chang, Y. S., Lalley, P. A., Nicholson, B. J., Willecke, K. <strong>Molecular cloning and functional expression of mouse connexin-30, a gap junction gene highly expressed in adult brain and skin.</strong> J. Biol. Chem. 271: 17903-17910, 1996. Note: Erratum: J. Biol. Chem. 271: 26444 only, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8663509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8663509</a>] [<a href="https://doi.org/10.1074/jbc.271.30.17903" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8663509">Dahl et al. (1996)</a> cloned a cDNA of a novel mouse connexin, gap junction protein beta-6 (Gjb6), which they called connexin-30 (Cx30). The Gjb6 gene, which is uninterrupted by introns, encodes a 261-amino acid protein that has 77% identity with mouse connexin-26 (GJB2; <a href="/entry/121011">121011</a>). In 4-week-old mice, Northern blot analysis revealed the expression of GJB6 most abundantly in brain and skin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8663509" 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="#8" class="mim-tip-reference" title="Grifa, A., Wagner, C. A., D'Ambrosio, L., Melchionda, S., Bernardi, F., Lopez-Bigas, N., Rabionet, R., Arbones, M., Monica, M. D., Estivill, X., Zelante, L., Lang, F., Gasparini, P. <strong>Mutations in GJB6 cause nonsyndromic autosomal dominant deafness at DFNA3 locus.</strong> Nature Genet. 23: 16-18, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10471490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10471490</a>] [<a href="https://doi.org/10.1038/12612" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10471490">Grifa et al. (1999)</a> cloned a cDNA fragment of human connexin-30 that encoded a 261-amino acid protein. The GJB6 protein shares 93% homology with mouse connexin-30 and 76% identity with human GJB2 (Cx26). Northern blot, RT-PCR, and in situ hybridization analyses revealed mouse Gjb6 expression in trachea, thyroid, brain, and cochlea. Using immunocytochemistry, <a href="#12" class="mim-tip-reference" title="Lautermann, J., Frank, H., Jahnke, K., Traub, O., Winterhager, E. <strong>Developmental expression patterns of connexin-26 and -30 in the rat cochlea.</strong> Dev. Genet. 25: 306-311, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10570462/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10570462</a>] [<a href="https://doi.org/10.1002/(SICI)1520-6408(1999)25:4<306::AID-DVG4>3.0.CO;2-R" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10570462">Lautermann et al. (1999)</a> detected Cx26 and Cx30 in the lateral wall of the cochlea of a 22-week-old human embryo. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10471490+10570462" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#2" class="mim-tip-reference" title="Dahl, E., Manthey, D., Chen, Y., Schwarz, H. J., Chang, Y. S., Lalley, P. A., Nicholson, B. J., Willecke, K. <strong>Molecular cloning and functional expression of mouse connexin-30, a gap junction gene highly expressed in adult brain and skin.</strong> J. Biol. Chem. 271: 17903-17910, 1996. Note: Erratum: J. Biol. Chem. 271: 26444 only, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8663509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8663509</a>] [<a href="https://doi.org/10.1074/jbc.271.30.17903" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8663509">Dahl et al. (1996)</a> assigned the Gjb6 gene to mouse chromosome 14 by somatic cell hybrid analysis. <a href="#8" class="mim-tip-reference" title="Grifa, A., Wagner, C. A., D'Ambrosio, L., Melchionda, S., Bernardi, F., Lopez-Bigas, N., Rabionet, R., Arbones, M., Monica, M. D., Estivill, X., Zelante, L., Lang, F., Gasparini, P. <strong>Mutations in GJB6 cause nonsyndromic autosomal dominant deafness at DFNA3 locus.</strong> Nature Genet. 23: 16-18, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10471490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10471490</a>] [<a href="https://doi.org/10.1038/12612" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10471490">Grifa et al. (1999)</a> noted that the mouse Gjb6 gene had been mapped to a region with syntenic homology to human chromosome 13q12 and that some deaf families linked to 13q12 are negative for mutations in GJB2, suggesting the presence of other deafness genes in the region. By FISH, <a href="#9" class="mim-tip-reference" title="Kelley, P. M., Abe, S., Askew, J. W., Smith, S. D., Usami, S., Kimberling, W. J. <strong>Human connexin 30 (GJB6), a candidate gene for nonsyndromic hearing loss: molecular cloning, tissue-specific expression, and assignment to chromosome 13q12.</strong> Genomics 62: 172-176, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10610709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10610709</a>] [<a href="https://doi.org/10.1006/geno.1999.6002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10610709">Kelley et al. (1999)</a> mapped the GJB6 gene to human chromosome 13q12. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10471490+10610709+8663509" 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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By SSCP mutation analysis in 198 deaf patients, including 38 families linked to 13q12, <a href="#8" class="mim-tip-reference" title="Grifa, A., Wagner, C. A., D'Ambrosio, L., Melchionda, S., Bernardi, F., Lopez-Bigas, N., Rabionet, R., Arbones, M., Monica, M. D., Estivill, X., Zelante, L., Lang, F., Gasparini, P. <strong>Mutations in GJB6 cause nonsyndromic autosomal dominant deafness at DFNA3 locus.</strong> Nature Genet. 23: 16-18, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10471490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10471490</a>] [<a href="https://doi.org/10.1038/12612" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10471490">Grifa et al. (1999)</a> identified a thr5-to-met (T5M) mutation (<a href="#0001">604418.0001</a>) in GJB6 in a family with autosomal dominant, bilateral, middle to high frequency hearing loss (DFNA3B; <a href="/entry/612643">612643</a>). The threonine at position 5 is conserved both evolutionarily and in human connexin-26. Electrophysiologic studies on Xenopus laevis oocytes determined that wildtype but not T5M mutant GJB6 produced gap junctional currents. When coexpressed, T5M mutant GJB6 suppressed wildtype transjunctional conductance in a dominant-negative manner. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10471490" 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="Kelley, P. M., Abe, S., Askew, J. W., Smith, S. D., Usami, S., Kimberling, W. J. <strong>Human connexin 30 (GJB6), a candidate gene for nonsyndromic hearing loss: molecular cloning, tissue-specific expression, and assignment to chromosome 13q12.</strong> Genomics 62: 172-176, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10610709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10610709</a>] [<a href="https://doi.org/10.1006/geno.1999.6002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10610709">Kelley et al. (1999)</a> detected no significant mutations in the GJB6 gene in a screening of 23 dominant families and 64 American and 30 Japanese recessive families with nonsyndromic hearing loss. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10610709" 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>Up to 50% of all patients with autosomal recessive nonsyndromic prelingual deafness in different populations have mutations in the GJB2 gene, which encodes connexin-26 and is situated at the locus arbitrarily designated DFNB1 (<a href="/entry/220290">220290</a>) on 13q12. However, a large fraction (10 to 42%) of patients with GJB2 mutations have only 1 mutant allele at that locus, with the accompanying mutation unidentified. DFNB1-linked familial cases with no mutation in GJB2 had also been reported. In a study of 33 unrelated probands with nonsyndromic prelingual deafness and only 1 mutant GJB2 allele, 9 subjects had evidence of linkage to DFNB1. <a href="#4" class="mim-tip-reference" title="del Castillo, I., Villamar, M., Moreno-Pelayo, M. A., del Castillo, F. J., Alvarez, A., Telleria, D., Menendez, I., Moreno, F. <strong>A deletion involving the connexin 30 gene in nonsyndromic hearing impairment.</strong> New Eng. J. Med. 346: 243-249, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11807148/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11807148</a>] [<a href="https://doi.org/10.1056/NEJMoa012052" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11807148">Del Castillo et al. (2002)</a> identified a 342-kb deletion in the GJB6 gene (<a href="#0004">604418.0004</a>), which encodes a protein, connexin-30, that is reported to be expressed with connexin-26 in the inner ear. The deletion extended distally to GJB2, which remained intact. The breakpoint junction of the deletion was isolated and sequenced, and a specific diagnostic test was developed for this common mutation. They found that 22 of the 33 subjects were heterozygous for both GJB6 and GJB2 mutations, including all 9 with evidence of linkage to the DFNB1 locus. Two subjects were homozygous for the GJB6 mutation. In the Spanish population, the 342-kb deletion in GJB6 was the second most frequent mutation causing prelingual deafness. The authors concluded that mutations in the complex DFNB1 locus, which contains 2 genes (GJB2 and GJB6), can result in a monogenic or in a digenic pattern of inheritance of prelingual deafness. <a href="#3" class="mim-tip-reference" title="del Castillo, F. J., Rodriguez-Ballesteros, M., Alvarez, A., Hutchin, T., Leonardi, E., de Oliveira, C. A., Azaiez, H., Brownstein, Z., Avenarius, M. R., Marlin, S., Pandya, A., Shahin, H., and 18 others. <strong>A novel deletion involving the connexin-30 gene, del(GJB6-d13s1854), found in trans with mutations in the GJB2 gene (connexin-26) in subjects with DFNB1 non-syndromic hearing impairment. (Letter)</strong> J. Med. Genet. 42: 588-594, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15994881/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15994881</a>] [<a href="https://doi.org/10.1136/jmg.2004.028324" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15994881">Del Castillo et al. (2005)</a> noted that the deletion size was 309 kb, according to more recent sequencing data. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15994881+11807148" 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 sporadic case of congenital profound deafness with no mutation in the GJB2 gene, <a href="#15" class="mim-tip-reference" title="Pallares-Ruiz, N., Blanchet, P., Mondain, M., Claustres, M., Roux, A.-F. <strong>A large deletion including most of GJB6 in recessive non syndromic deafness: a digenic effect?</strong> Europ. J. Hum. Genet. 10: 72-76, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11896458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11896458</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200762" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11896458">Pallares-Ruiz et al. (2002)</a> found a homozygous deletion including the 5-prime end of the GJB6 gene, covering at least 150 kb. This finding confirmed that homozygous absence of this gene is responsible for severe hearing impairment at the DFNB1 locus. Furthermore, <a href="#15" class="mim-tip-reference" title="Pallares-Ruiz, N., Blanchet, P., Mondain, M., Claustres, M., Roux, A.-F. <strong>A large deletion including most of GJB6 in recessive non syndromic deafness: a digenic effect?</strong> Europ. J. Hum. Genet. 10: 72-76, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11896458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11896458</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200762" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11896458">Pallares-Ruiz et al. (2002)</a> found the GJB6 deletion in trans in 4 of 6 deafness patients heterozygous for a GJB2 mutation, thereby suggesting a digenic mode of inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11896458" 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 255 French patients with a phenotype compatible with DFNB1, <a href="#7" class="mim-tip-reference" title="Feldmann, D., Denoyelle, F., Chauvin, P., Garabedian, E.-N., Couderc, R., Odent, S., Joannard, A., Schmerber, S., Delobel, B., Leman, J., Journel, H., Catros, H., and 20 others. <strong>Large deletion of the GJB6 gene in deaf patients heterozygous for the GJB2 gene mutation: genotypic and phenotypic analysis.</strong> Am. J. Med. Genet. 127A: 263-267, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15150777/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15150777</a>] [<a href="https://doi.org/10.1002/ajmg.a.20588" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15150777">Feldmann et al. (2004)</a> found that 32% had biallelic GJB2 mutations, and 6% were heterozygous for a GJB2 mutation and the GJB6 342-kb deletion. Profoundly deaf children were more likely to have the biallelic GJB2 or heterozygous GJB2/GJB6 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15150777" 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>Mutations in the GJB2 gene have been linked to sensorineural hearing loss either alone or as part of a syndrome. <a href="#14" class="mim-tip-reference" title="Marziano, N. K., Casalotti, S. O., Portelli, A. E., Becker, D. L., Forge, A. <strong>Mutations in the gene for connexin 26 (GJB2) that cause hearing loss have a dominant negative effect on connexin 30.</strong> Hum. Molec. Genet. 12: 805-812, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12668604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12668604</a>] [<a href="https://doi.org/10.1093/hmg/ddg076" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12668604">Marziano et al. (2003)</a> compared the properties of 4 CX26 mutants derived from point mutations associated with dominantly inherited hearing loss, either nonsyndromic (W44S, <a href="/entry/121011#0031">121011.0031</a>; R75W, <a href="/entry/121011#0011">121011.0011</a>) or with various skin disorders (G59A, <a href="/entry/121011#0015">121011.0015</a>; D66H, <a href="/entry/121011#0012">121011.0012</a>). Since CX26 and CX30 colocalize to the inner ear, the effect of the dominant CX26 mutations on both of these wildtype proteins was determined. Communication-deficient HeLa cells were transiently transfected with the various cDNA constructs, and dye transfer studies demonstrated disruption of intercellular coupling for all 4 CX26 mutant proteins. Immunostaining of the transfected cells revealed that G59A and D66H mutants had impaired intracellular trafficking and targeting to the plasma membrane. Impaired trafficking was rescued by oligomerization with both CX26 and CX30, suggesting that CX26 and CX30 can form heteromeric connexons. Significantly reduced dye transfer rates were observed between cells coexpressing either CX26 or CX30 together with W44S or R75W compared with wildtype proteins alone. The dominant actions of the G59A and D66H mutants were only on CX30 and CX26, respectively. <a href="#14" class="mim-tip-reference" title="Marziano, N. K., Casalotti, S. O., Portelli, A. E., Becker, D. L., Forge, A. <strong>Mutations in the gene for connexin 26 (GJB2) that cause hearing loss have a dominant negative effect on connexin 30.</strong> Hum. Molec. Genet. 12: 805-812, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12668604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12668604</a>] [<a href="https://doi.org/10.1093/hmg/ddg076" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12668604">Marziano et al. (2003)</a> suggested that in the inner ear CX26 and CX30 may form heteromeric connexons with particular properties essential for hearing and that disruption of these heteromeric channels underlies the nonsyndromic nature of certain deafness-causing GJB2 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12668604" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Clouston Syndrome</em></strong></p><p>
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<a href="#11" class="mim-tip-reference" title="Lamartine, J., Munhoz Essenfelder, G., Kibar, Z., Lanneluc, I., Callouet, E., Laoudj, D., Lemaitre, G., Hand, C., Haylick, S. J., Zonana, J., Antonarakis, S., Radhakrishna, U., Kelsell, D. P., Christianson, A. L., Pitaval, A., Der Kaloustian, V., Fraser, C., Blanchet-Bardon, C., Rouleau, G. A., Waksman, G. <strong>Mutations in GJB6 cause hidrotic ectodermal dysplasia. (Letter)</strong> Nature Genet. 26: 142-144, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11017065/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11017065</a>] [<a href="https://doi.org/10.1038/79851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11017065">Lamartine et al. (2000)</a> presented evidence that missense mutations in the GJB6 gene cause hidrotic ectodermal dysplasia (ECTD2; <a href="/entry/129500">129500</a>), also known as Clouston syndrome. This disease is an autosomal dominant skin disorder characterized by palmoplantar hyperkeratosis, hair defects (from partial to total alopecia), nail hypoplasia, and nail deformities. Clouston syndrome had been mapped to the pericentromeric region of 13q, where the GJB2 and GJB6 genes are located. Involvement of GJB2 in Clouston syndrome was excluded by <a href="#10" class="mim-tip-reference" title="Kelsell, D. P., Dunlop, J., Stevens, H. P., Lench, N. J., Liang, J. N., Parry, G., Mueller, R. F., Leigh, I. M. <strong>Connexin 26 mutations in hereditary non-syndromic sensorineural deafness.</strong> Nature 387: 80-83, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9139825/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9139825</a>] [<a href="https://doi.org/10.1038/387080a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9139825">Kelsell et al. (1997)</a>. GJB6 seemed to be a good candidate for the disorder because hearing impairment had been reported in a few cases of Clouston syndrome. In addition, expression of GJB6 had been observed in mouse epidermis (<a href="#2" class="mim-tip-reference" title="Dahl, E., Manthey, D., Chen, Y., Schwarz, H. J., Chang, Y. S., Lalley, P. A., Nicholson, B. J., Willecke, K. <strong>Molecular cloning and functional expression of mouse connexin-30, a gap junction gene highly expressed in adult brain and skin.</strong> J. Biol. Chem. 271: 17903-17910, 1996. Note: Erratum: J. Biol. Chem. 271: 26444 only, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8663509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8663509</a>] [<a href="https://doi.org/10.1074/jbc.271.30.17903" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8663509">Dahl et al., 1996</a>), and <a href="#11" class="mim-tip-reference" title="Lamartine, J., Munhoz Essenfelder, G., Kibar, Z., Lanneluc, I., Callouet, E., Laoudj, D., Lemaitre, G., Hand, C., Haylick, S. J., Zonana, J., Antonarakis, S., Radhakrishna, U., Kelsell, D. P., Christianson, A. L., Pitaval, A., Der Kaloustian, V., Fraser, C., Blanchet-Bardon, C., Rouleau, G. A., Waksman, G. <strong>Mutations in GJB6 cause hidrotic ectodermal dysplasia. (Letter)</strong> Nature Genet. 26: 142-144, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11017065/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11017065</a>] [<a href="https://doi.org/10.1038/79851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11017065">Lamartine et al. (2000)</a> detected a GJB6 transcript in human epidermal cells. They detected 2 missense mutations in the GJB6 gene: gly11 to arg (G11R; <a href="#0002">604418.0002</a>) and ala88 to val (A88V; <a href="#0003">604418.0003</a>). Affected individuals were heterozygous. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11017065+8663509+9139825" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Common, J. E. A., Becker, D., Di, W.-L., Leigh, I. M., O'Toole, E. A., Kelsell, D. P. <strong>Functional studies of human skin disease- and deafness-associated connexin 30 mutations.</strong> Biochem. Biophys. Res. Commun. 298: 651-656, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12419304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12419304</a>] [<a href="https://doi.org/10.1016/s0006-291x(02)02517-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12419304">Common et al. (2002)</a> transfected a keratinocyte cell line and HeLa cells with wildtype CX30 and CX30 mutants harboring disease-associated mutations. Mutations that result in skin disease, such as G11R (<a href="#0002">604418.0002</a>) and A88V (<a href="#0003">604418.0003</a>), impaired trafficking of the protein to the plasma membrane, thus preventing the formation of functional CX30 gap junctions. The deafness-associated mutation, T5M, resulted in correct trafficking of the protein to the membrane, but channel activity was impaired. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12419304" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Essenfelder, G. M., Bruzzone, R., Lamartine, J., Charollais, A., Blanchet-Bardon, C., Barbe, M. T., Meda, P., Waksman, G. <strong>Connexin30 mutations responsible for hidrotic ectodermal dysplasia cause abnormal hemichannel activity.</strong> Hum. Molec. Genet. 13: 1703-1714, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15213106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15213106</a>] [<a href="https://doi.org/10.1093/hmg/ddh191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15213106">Essenfelder et al. (2004)</a> analyzed the consequences of the G11R and A88V mutations on the functional properties of connexons. The distribution of CX30 was similar in affected palmoplantar skin and in normal epidermis. The presence of the wildtype protein improved trafficking of mutated CX30 to the plasma membrane where both G11R and A88V CX30 colocalized with wildtype CX30 and formed functional intercellular channels. Electrophysiologic properties of channels made of mutant CX30 differed slightly from those of wildtype CX30 but allowed for dye transfer between transfected HeLa cells. A gain of function was observed for G11R and A88V CX30, which formed functional hemichannels at the cell surface and, when expressed in HeLa cells, generated a leakage of ATP into the extracellular medium. <a href="#6" class="mim-tip-reference" title="Essenfelder, G. M., Bruzzone, R., Lamartine, J., Charollais, A., Blanchet-Bardon, C., Barbe, M. T., Meda, P., Waksman, G. <strong>Connexin30 mutations responsible for hidrotic ectodermal dysplasia cause abnormal hemichannel activity.</strong> Hum. Molec. Genet. 13: 1703-1714, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15213106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15213106</a>] [<a href="https://doi.org/10.1093/hmg/ddh191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15213106">Essenfelder et al. (2004)</a> suggested that such increased ATP levels might act as a paracrine messenger that, by altering the epidermal factors that control proliferation and differentiation of keratinocytes, could play a role in the pathophysiologic processes leading to the Clouston syndrome phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15213106" 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="#21" class="mim-tip-reference" title="Teubner, B., Michel, V., Pesch, J., Lautermann, J., Cohen-Salmon, M., Sohl, G., Jahnke, K., Winterhager, E., Herberhold, C., Hardelin, J.-P., Petit, C., Willecke, K. <strong>Connexin30 (Gjb6)-deficiency causes severe hearing impairment and lack of endocochlear potential.</strong> Hum. Molec. Genet. 12: 13-21, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12490528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12490528</a>] [<a href="https://doi.org/10.1093/hmg/ddg001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12490528">Teubner et al. (2003)</a> generated Gjb6-deficient mice by deletion of the Gjb6 coding region. Homozygous null mutants were born at the expected Mendelian frequency, developed normally, and were fertile; however, they exhibited a severe constitutive hearing impairment. From the age of hearing onset, these mice lacked the electrical potential difference between the endolymphatic and perilymphatic compartments of the cochlea (i.e., the endocochlear potential), which plays a key role in the high sensitivity of the mammalian auditory organ. In addition, after postnatal day 18, the cochlear sensory epithelium started to degenerate by cell apoptosis. <a href="#21" class="mim-tip-reference" title="Teubner, B., Michel, V., Pesch, J., Lautermann, J., Cohen-Salmon, M., Sohl, G., Jahnke, K., Winterhager, E., Herberhold, C., Hardelin, J.-P., Petit, C., Willecke, K. <strong>Connexin30 (Gjb6)-deficiency causes severe hearing impairment and lack of endocochlear potential.</strong> Hum. Molec. Genet. 12: 13-21, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12490528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12490528</a>] [<a href="https://doi.org/10.1093/hmg/ddg001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12490528">Teubner et al. (2003)</a> concluded that the Gjb6 null phenotype revealed a critical role of GJB6 both in generating the endocochlear potential and for survival of the auditory hair cells after the onset of hearing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12490528" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using homologous recombination, <a href="#16" class="mim-tip-reference" title="Schutz, M., Scimemi, P., Majumder, P., De Siati, R. D., Crispino, G., Rodriguez, L., Bortolozzi, M., Santarelli, R., Seydel, A., Sonntag, S., Ingham, N., Steel, K. P., Willecke, K., Mammano, F. <strong>The human deafness-associated connexin 30 T5M mutation causes mild hearing loss and reduces biochemical coupling among cochlear non-sensory cells in knock-in mice.</strong> Hum. Molec. Genet. 19: 4759-4773, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20858605/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20858605</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20858605[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/10.1093/hmg/ddq402" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20858605">Schutz et al. (2010)</a> created a line of mice expressing human CX30 with the T5M substitution (<a href="#0001">604418.0001</a>). Homozygous CX30-T5M mice were born at the expected mendelian ratio and were viable and fertile. In contrast to patients with a heterozygous T5M substitution, homozygous CX30-T5M mice showed only mild hearing impairment, with significantly increased hearing thresholds of about 15 decibels at all frequencies. In adult homozygous mice, CX30-T5M expression was reduced by approximately one-third compared with wildtype Cx30 levels, concomitant with downregulation of Cx26. CX30-T5M was expressed at cell membranes and formed gap junctions, and homozygous CX30-T5M mice showed normal endocochlear potentials. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20858605" 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>.0001 DEAFNESS, AUTOSOMAL DOMINANT 3B (1 family)</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894414 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894414;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104894414?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894414" 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=rs104894414" 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=RCV000088666" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000088666" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000088666</a>
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<p>In affected members of an Italian family with sensorineural hearing loss and linkage to chromosome 13q12 (DFNA3B; <a href="/entry/612643">612643</a>), <a href="#8" class="mim-tip-reference" title="Grifa, A., Wagner, C. A., D'Ambrosio, L., Melchionda, S., Bernardi, F., Lopez-Bigas, N., Rabionet, R., Arbones, M., Monica, M. D., Estivill, X., Zelante, L., Lang, F., Gasparini, P. <strong>Mutations in GJB6 cause nonsyndromic autosomal dominant deafness at DFNA3 locus.</strong> Nature Genet. 23: 16-18, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10471490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10471490</a>] [<a href="https://doi.org/10.1038/12612" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10471490">Grifa et al. (1999)</a> identified a heterozygous C-to-T transition in the GJB6 gene, resulting in a thr5-to-met (T5M) substitution. In vitro functional expression studies in Xenopus oocytes showed that the mutant protein did not induce membrane potential coupling and suppressed the wildtype protein, consistent with a dominant-negative effect. The authors postulated that the negative inhibitory effect was due to direct interaction of intact and defective connexins at the plasma membrane level. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10471490" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using homologous recombination, <a href="#16" class="mim-tip-reference" title="Schutz, M., Scimemi, P., Majumder, P., De Siati, R. D., Crispino, G., Rodriguez, L., Bortolozzi, M., Santarelli, R., Seydel, A., Sonntag, S., Ingham, N., Steel, K. P., Willecke, K., Mammano, F. <strong>The human deafness-associated connexin 30 T5M mutation causes mild hearing loss and reduces biochemical coupling among cochlear non-sensory cells in knock-in mice.</strong> Hum. Molec. Genet. 19: 4759-4773, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20858605/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20858605</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20858605[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/10.1093/hmg/ddq402" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20858605">Schutz et al. (2010)</a> created a line of mice expressing human CX30 with the T5M substitution. Homozygous CX30-T5M mice were born at the expected mendelian ratio and were viable and fertile. In contrast to patients with a heterozygous T5M substitution, the homozygous CX30-T5M mice showed only mild hearing impairment, with significantly increased hearing thresholds of about 15 decibels at all frequencies. In adult homozygous mice, CX30-T5M expression was reduced by approximately one-third compared with wildtype Cx30 levels, concomitant with downregulation of Cx26. CX30-T5M was expressed at cell membranes and formed gap junctions, and homozygous CX30-T5M mice showed normal endocochlear potentials. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20858605" 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>.0002 ECTODERMAL DYSPLASIA, HIDROTIC</strong>
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GJB6, GLY11ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894415 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894415;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104894415?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894415" 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=rs104894415" 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=RCV000005882 OR RCV000255581 OR RCV000645727 OR RCV003335016" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005882, RCV000255581, RCV000645727, RCV003335016" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005882...</a>
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<p>In 2 unrelated French families segregating a typical form of hidrotic ectodermal dysplasia (<a href="/entry/129500">129500</a>), <a href="#11" class="mim-tip-reference" title="Lamartine, J., Munhoz Essenfelder, G., Kibar, Z., Lanneluc, I., Callouet, E., Laoudj, D., Lemaitre, G., Hand, C., Haylick, S. J., Zonana, J., Antonarakis, S., Radhakrishna, U., Kelsell, D. P., Christianson, A. L., Pitaval, A., Der Kaloustian, V., Fraser, C., Blanchet-Bardon, C., Rouleau, G. A., Waksman, G. <strong>Mutations in GJB6 cause hidrotic ectodermal dysplasia. (Letter)</strong> Nature Genet. 26: 142-144, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11017065/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11017065</a>] [<a href="https://doi.org/10.1038/79851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11017065">Lamartine et al. (2000)</a> found, in the GJB6 gene, a 31G-A transition leading to a gly11-to-arg (G11R) missense mutation. They analyzed 10 additional unrelated affected individuals of various geographic origins and found the same mutation in 1 African, 1 Spanish, 3 French-Canadian, 1 Scottish-Irish, and 1 additional French case. Three other patients had another missense mutation, ala88 to val (<a href="#0003">604418.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11017065" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 ECTODERMAL DYSPLASIA, HIDROTIC</strong>
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GJB6, ALA88VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28937872 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937872;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs28937872?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28937872" 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=rs28937872" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005883 OR RCV000798432 OR RCV002504751" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005883, RCV000798432, RCV002504751" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005883...</a>
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<p>In 3 patients with hidrotic ectodermal dysplasia (<a href="/entry/129500">129500</a>) originating from India, Malaysia, and Wales, <a href="#11" class="mim-tip-reference" title="Lamartine, J., Munhoz Essenfelder, G., Kibar, Z., Lanneluc, I., Callouet, E., Laoudj, D., Lemaitre, G., Hand, C., Haylick, S. J., Zonana, J., Antonarakis, S., Radhakrishna, U., Kelsell, D. P., Christianson, A. L., Pitaval, A., Der Kaloustian, V., Fraser, C., Blanchet-Bardon, C., Rouleau, G. A., Waksman, G. <strong>Mutations in GJB6 cause hidrotic ectodermal dysplasia. (Letter)</strong> Nature Genet. 26: 142-144, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11017065/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11017065</a>] [<a href="https://doi.org/10.1038/79851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11017065">Lamartine et al. (2000)</a> found a 263C-T transition in the GJB6 gene leading to an ala88-to-val (A88V) missense mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11017065" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 DEAFNESS, AUTOSOMAL RECESSIVE 1B</strong>
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DEAFNESS, DIGENIC, GJB2/GJB6, INCLUDED
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GJB6, 309-KB DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005884 OR RCV000005885 OR RCV000239454" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005884, RCV000005885, RCV000239454" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005884...</a>
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<p>In 2 Spanish sibs with autosomal recessive deafness-1B (DFNB1B; <a href="/entry/612645">612645</a>), <a href="#4" class="mim-tip-reference" title="del Castillo, I., Villamar, M., Moreno-Pelayo, M. A., del Castillo, F. J., Alvarez, A., Telleria, D., Menendez, I., Moreno, F. <strong>A deletion involving the connexin 30 gene in nonsyndromic hearing impairment.</strong> New Eng. J. Med. 346: 243-249, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11807148/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11807148</a>] [<a href="https://doi.org/10.1056/NEJMoa012052" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11807148">del Castillo et al. (2002)</a> identified homozygosity for a 342-kb deletion (342-KB DEL) in the GJB6 gene. The parents, who were deaf, were both found to be compound heterozygous for the GJB6 deletion and a common mutation in the GJB2 gene (35delG; <a href="/entry/121011#0005">121011.0005</a>), consistent with digenic inheritance (see <a href="/entry/220290">220290</a>). A heterozygous GJB6 deletion was also identified in 22 of 33 additional Spanish patients with only 1 mutant GJB2 allele, again consistent with digenic inheritance due to compound heterozygous mutations in 2 different genes. <a href="#3" class="mim-tip-reference" title="del Castillo, F. J., Rodriguez-Ballesteros, M., Alvarez, A., Hutchin, T., Leonardi, E., de Oliveira, C. A., Azaiez, H., Brownstein, Z., Avenarius, M. R., Marlin, S., Pandya, A., Shahin, H., and 18 others. <strong>A novel deletion involving the connexin-30 gene, del(GJB6-d13s1854), found in trans with mutations in the GJB2 gene (connexin-26) in subjects with DFNB1 non-syndromic hearing impairment. (Letter)</strong> J. Med. Genet. 42: 588-594, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15994881/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15994881</a>] [<a href="https://doi.org/10.1136/jmg.2004.028324" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15994881">Del Castillo et al. (2005)</a> noted that the deletion size was 309 kb, according to more recent sequencing data. This deletion truncating the GJB6 gene was shown to be the accompanying mutation in approximately 50% of deaf GJB2 heterozygotes in a cohort of Spanish patients, thus becoming second only to 35delG at GJB2 as the most frequent mutation causing prelingual hearing impairment in Spain. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15994881+11807148" 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 multicenter study in 9 countries, <a href="#5" class="mim-tip-reference" title="del Castillo, Moreno-Pelayo, M. A., del Castillo, F. J., Brownstein, Z., Marlin, S., Adina, Q., Cockburn, D. J., Pandya, A., Siemering, K. R., Chamberlin, G. P., Ballana, E., Wuyts, W., and 16 others. <strong>Prevalence and evolutionary origins of the del(GJB6-D13S1830) mutation in the DFNB1 locus in hearing-impaired subjects: a multicenter study.</strong> Am. J. Hum. Genet. 73: 1452-1458, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14571368/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14571368</a>] [<a href="https://doi.org/10.1086/380205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14571368">del Castillo et al. (2003)</a> showed that the GJB6 deletion was present in most of the screening populations, with higher frequencies in France, Spain, and Israel where the percentages of unexplained GJB2 heterozygotes fell to 16 to 20.9% after screening for the GJB6 deletion mutation. Analysis of haplotypes associated with the deletion revealed a founder effect in Ashkenazi Jews and also suggested a common founder for countries in western Europe (the deletion mutation was referred to as del(GJB6-D13S1830) by <a href="#5" class="mim-tip-reference" title="del Castillo, Moreno-Pelayo, M. A., del Castillo, F. J., Brownstein, Z., Marlin, S., Adina, Q., Cockburn, D. J., Pandya, A., Siemering, K. R., Chamberlin, G. P., Ballana, E., Wuyts, W., and 16 others. <strong>Prevalence and evolutionary origins of the del(GJB6-D13S1830) mutation in the DFNB1 locus in hearing-impaired subjects: a multicenter study.</strong> Am. J. Hum. Genet. 73: 1452-1458, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14571368/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14571368</a>] [<a href="https://doi.org/10.1086/380205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14571368">del Castillo et al. (2003)</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14571368" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Seeman, P., Bendova, O., Raskova, D., Malikova, M., Groh, D., Kabelka, Z. <strong>Double heterozygosity with mutations involving both the GJB2 and GJB6 genes is a possible, but very rare, cause of congenital deafness in the Czech population.</strong> Ann. Hum. Genet. 69: 9-14, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15638823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15638823</a>] [<a href="https://doi.org/10.1046/j.1529-8817.2003.00120.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15638823">Seeman et al. (2005)</a> identified the 342-kb deletion in the GJB6 gene in 1 of 13 Czech patients with prelingual nonsyndromic sensorineural deafness who also carried 1 pathogenic mutation in the GJB2 gene. The deletion was not detected in 600 control chromosomes from Czech individuals with normal hearing. <a href="#17" class="mim-tip-reference" title="Seeman, P., Bendova, O., Raskova, D., Malikova, M., Groh, D., Kabelka, Z. <strong>Double heterozygosity with mutations involving both the GJB2 and GJB6 genes is a possible, but very rare, cause of congenital deafness in the Czech population.</strong> Ann. Hum. Genet. 69: 9-14, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15638823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15638823</a>] [<a href="https://doi.org/10.1046/j.1529-8817.2003.00120.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15638823">Seeman et al. (2005)</a> concluded that the 342-kb deletion is very rare in central Europe compared to reports from Spain, France, and Israel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15638823" 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 324 probands with hearing loss and 280 controls, including 135 probands and 280 controls previously reported by <a href="#20" class="mim-tip-reference" title="Tang, H.-Y., Fang, P., Ward, P. A., Schmitt, E., Darilek, S., Manolidis, S., Oghalai, J. S., Roa, B. B., Alford, R. L. <strong>DNA sequence analysis of GJB2, encoding connexin 26: observations from a population of hearing impaired cases and variable carrier rates, complex genotypes, and ethnic stratification of alleles among controls.</strong> Am. J. Med. Genet. 140A: 2401-2415, 2006. Note: Erratum: Am. J. Med. Genet. 146A: 2979 only, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17041943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17041943</a>] [<a href="https://doi.org/10.1002/ajmg.a.31525" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17041943">Tang et al. (2006)</a>, <a href="#19" class="mim-tip-reference" title="Tang, H.-Y., Basehore, M. J., Blakey, G. L., Darilek, S., Oghalai, J. S., Roa, B. B., Fang, P., Alford, R. L. <strong>Infrequency of two deletion mutations at the DFNB1 locus in patients and controls.</strong> Am. J. Med. Genet. 146A: 934-936, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18324688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18324688</a>] [<a href="https://doi.org/10.1002/ajmg.a.32207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18324688">Tang et al. (2008)</a> screened for DNA sequence variations in GJB2 and for deletions in GJB6. The 232-kb GJB6 deletion (<a href="#0006">604418.0006</a>) was not found, and the 309-kb GJB6 deletion was found only once, in a patient of unknown ethnicity who was also heterozygous for a truncating mutation in the GJB2 gene. <a href="#19" class="mim-tip-reference" title="Tang, H.-Y., Basehore, M. J., Blakey, G. L., Darilek, S., Oghalai, J. S., Roa, B. B., Fang, P., Alford, R. L. <strong>Infrequency of two deletion mutations at the DFNB1 locus in patients and controls.</strong> Am. J. Med. Genet. 146A: 934-936, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18324688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18324688</a>] [<a href="https://doi.org/10.1002/ajmg.a.32207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18324688">Tang et al. (2008)</a> suggested that the 232- and 309-kb deletions in the GJB6 gene may not be common in all populations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17041943+18324688" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894416 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894416;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104894416?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894416" 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=rs104894416" 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=RCV000005886" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005886" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005886</a>
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<p><a href="#18" class="mim-tip-reference" title="Smith, F. J. D., Morley, S. M., McLean, W. H. I. <strong>A novel connexin 30 mutation in Clouston syndrome.</strong> J. Invest. Derm. 118: 530-532, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11874494/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11874494</a>] [<a href="https://doi.org/10.1046/j.0022-202x.2001.01689.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11874494">Smith et al. (2002)</a> reported a novel mutation, val37 to glu (V37E), within the first transmembrane domain of connexin-30 in a spontaneous case of Clouston syndrome (ECTD2; <a href="/entry/129500">129500</a>). The amino acid substitution arose from a heterozygous 110T-to-A transversion in the GJB6 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11874494" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 DEAFNESS, DIGENIC, GJB2/GJB6</strong>
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<p>In 4 unrelated Spanish patients with autosomal recessive nonsyndromic hearing impairment who were heterozygous for 1 GJB2 (<a href="/entry/121011">121011</a>) mutant allele and did not carry the 309-kb GJB6 deletion (<a href="#0004">604418.0004</a>), <a href="#3" class="mim-tip-reference" title="del Castillo, F. J., Rodriguez-Ballesteros, M., Alvarez, A., Hutchin, T., Leonardi, E., de Oliveira, C. A., Azaiez, H., Brownstein, Z., Avenarius, M. R., Marlin, S., Pandya, A., Shahin, H., and 18 others. <strong>A novel deletion involving the connexin-30 gene, del(GJB6-d13s1854), found in trans with mutations in the GJB2 gene (connexin-26) in subjects with DFNB1 non-syndromic hearing impairment. (Letter)</strong> J. Med. Genet. 42: 588-594, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15994881/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15994881</a>] [<a href="https://doi.org/10.1136/jmg.2004.028324" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15994881">del Castillo et al. (2005)</a> identified a 232-kb deletion, which they referred to as del(GJB6-D13S1854). The findings were consistent with digenic inheritance (see <a href="/entry/220290">220290</a>). The 232-kb deletion was identified in trans in 12 of 47 unrelated affected Spanish individuals who were unresolved GJB2 heterozygotes. The deletion was not found in 100 control subjects with normal hearing. The 232-kb deletion was found to account for 22.2% of affected GJB2 heterozygotes who were unresolved after screening for the 309-kb deletion in the United Kingdom, for 6.3% in Brazil, and for 1.9% in northern Italy. By haplotype analysis, <a href="#3" class="mim-tip-reference" title="del Castillo, F. J., Rodriguez-Ballesteros, M., Alvarez, A., Hutchin, T., Leonardi, E., de Oliveira, C. A., Azaiez, H., Brownstein, Z., Avenarius, M. R., Marlin, S., Pandya, A., Shahin, H., and 18 others. <strong>A novel deletion involving the connexin-30 gene, del(GJB6-d13s1854), found in trans with mutations in the GJB2 gene (connexin-26) in subjects with DFNB1 non-syndromic hearing impairment. (Letter)</strong> J. Med. Genet. 42: 588-594, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15994881/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15994881</a>] [<a href="https://doi.org/10.1136/jmg.2004.028324" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15994881">del Castillo et al. (2005)</a> showed a common founder for the 232-kb deletion in Spain, the United Kingdom, and Italy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15994881" 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 324 probands with hearing loss and 280 controls, including 135 probands and 280 controls previously reported by <a href="#20" class="mim-tip-reference" title="Tang, H.-Y., Fang, P., Ward, P. A., Schmitt, E., Darilek, S., Manolidis, S., Oghalai, J. S., Roa, B. B., Alford, R. L. <strong>DNA sequence analysis of GJB2, encoding connexin 26: observations from a population of hearing impaired cases and variable carrier rates, complex genotypes, and ethnic stratification of alleles among controls.</strong> Am. J. Med. Genet. 140A: 2401-2415, 2006. Note: Erratum: Am. J. Med. Genet. 146A: 2979 only, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17041943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17041943</a>] [<a href="https://doi.org/10.1002/ajmg.a.31525" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17041943">Tang et al. (2006)</a>, <a href="#19" class="mim-tip-reference" title="Tang, H.-Y., Basehore, M. J., Blakey, G. L., Darilek, S., Oghalai, J. S., Roa, B. B., Fang, P., Alford, R. L. <strong>Infrequency of two deletion mutations at the DFNB1 locus in patients and controls.</strong> Am. J. Med. Genet. 146A: 934-936, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18324688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18324688</a>] [<a href="https://doi.org/10.1002/ajmg.a.32207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18324688">Tang et al. (2008)</a> screened for DNA sequence variations in GJB2 and for deletions in GJB6. The 232-kb GJB6 deletion was not found, and the 309-kb GJB6 deletion was found only once, in a patient of unknown ethnicity who was also heterozygous for a Q57X mutation in GJB2. <a href="#19" class="mim-tip-reference" title="Tang, H.-Y., Basehore, M. J., Blakey, G. L., Darilek, S., Oghalai, J. S., Roa, B. B., Fang, P., Alford, R. L. <strong>Infrequency of two deletion mutations at the DFNB1 locus in patients and controls.</strong> Am. J. Med. Genet. 146A: 934-936, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18324688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18324688</a>] [<a href="https://doi.org/10.1002/ajmg.a.32207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18324688">Tang et al. (2008)</a> suggested that the 232- and 309-kb deletions in the GJB6 gene may not be common in all populations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17041943+18324688" 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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Common, J. E. A., Becker, D., Di, W.-L., Leigh, I. M., O'Toole, E. A., Kelsell, D. P.
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<strong>Functional studies of human skin disease- and deafness-associated connexin 30 mutations.</strong>
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Biochem. Biophys. Res. Commun. 298: 651-656, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12419304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12419304</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12419304" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0006-291x(02)02517-2" target="_blank">Full Text</a>]
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Dahl, E., Manthey, D., Chen, Y., Schwarz, H. J., Chang, Y. S., Lalley, P. A., Nicholson, B. J., Willecke, K.
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<strong>Molecular cloning and functional expression of mouse connexin-30, a gap junction gene highly expressed in adult brain and skin.</strong>
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J. Biol. Chem. 271: 17903-17910, 1996. Note: Erratum: J. Biol. Chem. 271: 26444 only, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8663509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8663509</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8663509" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.271.30.17903" target="_blank">Full Text</a>]
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del Castillo, F. J., Rodriguez-Ballesteros, M., Alvarez, A., Hutchin, T., Leonardi, E., de Oliveira, C. A., Azaiez, H., Brownstein, Z., Avenarius, M. R., Marlin, S., Pandya, A., Shahin, H., and 18 others.
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<strong>A novel deletion involving the connexin-30 gene, del(GJB6-d13s1854), found in trans with mutations in the GJB2 gene (connexin-26) in subjects with DFNB1 non-syndromic hearing impairment. (Letter)</strong>
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J. Med. Genet. 42: 588-594, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15994881/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15994881</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15994881" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/380205" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/ddh191" target="_blank">Full Text</a>]
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<a id="20" class="mim-anchor"></a>
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<a id="Tang2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tang, H.-Y., Fang, P., Ward, P. A., Schmitt, E., Darilek, S., Manolidis, S., Oghalai, J. S., Roa, B. B., Alford, R. L.
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<strong>DNA sequence analysis of GJB2, encoding connexin 26: observations from a population of hearing impaired cases and variable carrier rates, complex genotypes, and ethnic stratification of alleles among controls.</strong>
|
|
Am. J. Med. Genet. 140A: 2401-2415, 2006. Note: Erratum: Am. J. Med. Genet. 146A: 2979 only, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17041943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17041943</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17041943" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.31525" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="21" class="mim-anchor"></a>
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<a id="Teubner2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Teubner, B., Michel, V., Pesch, J., Lautermann, J., Cohen-Salmon, M., Sohl, G., Jahnke, K., Winterhager, E., Herberhold, C., Hardelin, J.-P., Petit, C., Willecke, K.
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|
<strong>Connexin30 (Gjb6)-deficiency causes severe hearing impairment and lack of endocochlear potential.</strong>
|
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Hum. Molec. Genet. 12: 13-21, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12490528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12490528</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12490528" 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/ddg001" target="_blank">Full Text</a>]
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</p>
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</div>
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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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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Patricia A. Hartz - updated : 1/15/2014
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 10/27/2008<br>George E. Tiller - updated : 1/16/2007<br>Marla J. F. O'Neill - updated : 9/19/2005<br>Victor A. McKusick - updated : 6/3/2005<br>George E. Tiller - updated : 2/18/2005<br>Natalie E. Krasikov - updated : 11/2/2004<br>George E. Tiller - updated : 10/26/2004<br>Victor A. McKusick - updated : 1/5/2004<br>Gary A. Bellus - updated : 4/14/2003<br>Patricia A. Hartz - updated : 12/17/2002<br>Michael B. Petersen - updated : 4/30/2002<br>Victor A. McKusick - updated : 1/30/2002<br>Victor A. McKusick - updated : 9/20/2000<br>Paul J. Converse - updated : 1/12/2000
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Paul J. Converse : 1/11/2000
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 05/26/2022
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 10/10/2014<br>carol : 1/28/2014<br>carol : 1/28/2014<br>mgross : 1/16/2014<br>mcolton : 1/15/2014<br>carol : 3/6/2009<br>ckniffin : 3/3/2009<br>terry : 12/12/2008<br>terry : 12/2/2008<br>wwang : 11/3/2008<br>terry : 10/27/2008<br>joanna : 10/8/2008<br>wwang : 1/23/2007<br>terry : 1/16/2007<br>wwang : 10/5/2005<br>terry : 9/19/2005<br>tkritzer : 6/9/2005<br>terry : 6/3/2005<br>carol : 3/4/2005<br>wwang : 3/2/2005<br>terry : 2/18/2005<br>carol : 11/2/2004<br>tkritzer : 10/26/2004<br>cwells : 1/6/2004<br>terry : 1/5/2004<br>alopez : 4/14/2003<br>mgross : 12/18/2002<br>terry : 12/17/2002<br>cwells : 5/2/2002<br>cwells : 4/30/2002<br>cwells : 4/30/2002<br>alopez : 2/6/2002<br>terry : 1/30/2002<br>carol : 11/15/2000<br>alopez : 9/26/2000<br>alopez : 9/25/2000<br>terry : 9/20/2000<br>carol : 1/18/2000<br>carol : 1/13/2000<br>carol : 1/12/2000<br>carol : 1/12/2000<br>carol : 1/11/2000<br>carol : 1/11/2000
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 604418
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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GAP JUNCTION PROTEIN, BETA-6; GJB6
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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CONNEXIN 30; CX30
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: GJB6</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 54209007;
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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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<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: 13q12.11
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|
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Genomic coordinates <span class="small">(GRCh38)</span> : 13:20,221,962-20,232,319 </span>
|
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</em>
|
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</strong>
|
|
<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
|
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<div>
|
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
|
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<tr class="active">
|
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<th>
|
|
Location
|
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</th>
|
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<th>
|
|
Phenotype
|
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</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
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</th>
|
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<th>
|
|
Inheritance
|
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</th>
|
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<th>
|
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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="4">
|
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<span class="mim-font">
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13q12.11
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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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Deafness, autosomal dominant 3B
|
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</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
612643
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
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3
|
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</span>
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</td>
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</tr>
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<tr>
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<td>
|
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<span class="mim-font">
|
|
Deafness, autosomal recessive 1B
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
612645
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
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3
|
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</span>
|
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</td>
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</tr>
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<tr>
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<td>
|
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<span class="mim-font">
|
|
Deafness, digenic GJB2/GJB6
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
220290
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive; Digenic dominant
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
3
|
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</span>
|
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</td>
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</tr>
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<tr>
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<td>
|
|
<span class="mim-font">
|
|
Ectodermal dysplasia 2, Clouston type
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
129500
|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>The connexin gene family codes for the protein subunits of gap junction channels that mediate direct diffusion of ions and metabolites between the cytoplasm of adjacent cells. Connexins span the plasma membrane 4 times, with amino- and carboxy-terminal regions facing the cytoplasm. Connexin genes are expressed in a cell type-specific manner with overlapping specificity. The gap junction channels have unique properties depending on the type of connexins constituting the channel. Connexin-30 (GJB6) is a gap junction subunit expressed abundantly in brain and cochlea (summary by Dahl et al., 1996; Lautermann et al., 1998). </p>
|
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</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
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</h4>
|
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</div>
|
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<span class="mim-text-font">
|
|
<p>Dahl et al. (1996) cloned a cDNA of a novel mouse connexin, gap junction protein beta-6 (Gjb6), which they called connexin-30 (Cx30). The Gjb6 gene, which is uninterrupted by introns, encodes a 261-amino acid protein that has 77% identity with mouse connexin-26 (GJB2; 121011). In 4-week-old mice, Northern blot analysis revealed the expression of GJB6 most abundantly in brain and skin. </p><p>Grifa et al. (1999) cloned a cDNA fragment of human connexin-30 that encoded a 261-amino acid protein. The GJB6 protein shares 93% homology with mouse connexin-30 and 76% identity with human GJB2 (Cx26). Northern blot, RT-PCR, and in situ hybridization analyses revealed mouse Gjb6 expression in trachea, thyroid, brain, and cochlea. Using immunocytochemistry, Lautermann et al. (1999) detected Cx26 and Cx30 in the lateral wall of the cochlea of a 22-week-old human embryo. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<span class="mim-text-font">
|
|
<p>Dahl et al. (1996) assigned the Gjb6 gene to mouse chromosome 14 by somatic cell hybrid analysis. Grifa et al. (1999) noted that the mouse Gjb6 gene had been mapped to a region with syntenic homology to human chromosome 13q12 and that some deaf families linked to 13q12 are negative for mutations in GJB2, suggesting the presence of other deafness genes in the region. By FISH, Kelley et al. (1999) mapped the GJB6 gene to human chromosome 13q12. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p><strong><em>Deafness, Autosomal Dominant/Autosomal Recessive</em></strong></p><p>
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By SSCP mutation analysis in 198 deaf patients, including 38 families linked to 13q12, Grifa et al. (1999) identified a thr5-to-met (T5M) mutation (604418.0001) in GJB6 in a family with autosomal dominant, bilateral, middle to high frequency hearing loss (DFNA3B; 612643). The threonine at position 5 is conserved both evolutionarily and in human connexin-26. Electrophysiologic studies on Xenopus laevis oocytes determined that wildtype but not T5M mutant GJB6 produced gap junctional currents. When coexpressed, T5M mutant GJB6 suppressed wildtype transjunctional conductance in a dominant-negative manner. </p><p>Kelley et al. (1999) detected no significant mutations in the GJB6 gene in a screening of 23 dominant families and 64 American and 30 Japanese recessive families with nonsyndromic hearing loss. </p><p>Up to 50% of all patients with autosomal recessive nonsyndromic prelingual deafness in different populations have mutations in the GJB2 gene, which encodes connexin-26 and is situated at the locus arbitrarily designated DFNB1 (220290) on 13q12. However, a large fraction (10 to 42%) of patients with GJB2 mutations have only 1 mutant allele at that locus, with the accompanying mutation unidentified. DFNB1-linked familial cases with no mutation in GJB2 had also been reported. In a study of 33 unrelated probands with nonsyndromic prelingual deafness and only 1 mutant GJB2 allele, 9 subjects had evidence of linkage to DFNB1. Del Castillo et al. (2002) identified a 342-kb deletion in the GJB6 gene (604418.0004), which encodes a protein, connexin-30, that is reported to be expressed with connexin-26 in the inner ear. The deletion extended distally to GJB2, which remained intact. The breakpoint junction of the deletion was isolated and sequenced, and a specific diagnostic test was developed for this common mutation. They found that 22 of the 33 subjects were heterozygous for both GJB6 and GJB2 mutations, including all 9 with evidence of linkage to the DFNB1 locus. Two subjects were homozygous for the GJB6 mutation. In the Spanish population, the 342-kb deletion in GJB6 was the second most frequent mutation causing prelingual deafness. The authors concluded that mutations in the complex DFNB1 locus, which contains 2 genes (GJB2 and GJB6), can result in a monogenic or in a digenic pattern of inheritance of prelingual deafness. Del Castillo et al. (2005) noted that the deletion size was 309 kb, according to more recent sequencing data. </p><p>In a sporadic case of congenital profound deafness with no mutation in the GJB2 gene, Pallares-Ruiz et al. (2002) found a homozygous deletion including the 5-prime end of the GJB6 gene, covering at least 150 kb. This finding confirmed that homozygous absence of this gene is responsible for severe hearing impairment at the DFNB1 locus. Furthermore, Pallares-Ruiz et al. (2002) found the GJB6 deletion in trans in 4 of 6 deafness patients heterozygous for a GJB2 mutation, thereby suggesting a digenic mode of inheritance. </p><p>In 255 French patients with a phenotype compatible with DFNB1, Feldmann et al. (2004) found that 32% had biallelic GJB2 mutations, and 6% were heterozygous for a GJB2 mutation and the GJB6 342-kb deletion. Profoundly deaf children were more likely to have the biallelic GJB2 or heterozygous GJB2/GJB6 mutations. </p><p>Mutations in the GJB2 gene have been linked to sensorineural hearing loss either alone or as part of a syndrome. Marziano et al. (2003) compared the properties of 4 CX26 mutants derived from point mutations associated with dominantly inherited hearing loss, either nonsyndromic (W44S, 121011.0031; R75W, 121011.0011) or with various skin disorders (G59A, 121011.0015; D66H, 121011.0012). Since CX26 and CX30 colocalize to the inner ear, the effect of the dominant CX26 mutations on both of these wildtype proteins was determined. Communication-deficient HeLa cells were transiently transfected with the various cDNA constructs, and dye transfer studies demonstrated disruption of intercellular coupling for all 4 CX26 mutant proteins. Immunostaining of the transfected cells revealed that G59A and D66H mutants had impaired intracellular trafficking and targeting to the plasma membrane. Impaired trafficking was rescued by oligomerization with both CX26 and CX30, suggesting that CX26 and CX30 can form heteromeric connexons. Significantly reduced dye transfer rates were observed between cells coexpressing either CX26 or CX30 together with W44S or R75W compared with wildtype proteins alone. The dominant actions of the G59A and D66H mutants were only on CX30 and CX26, respectively. Marziano et al. (2003) suggested that in the inner ear CX26 and CX30 may form heteromeric connexons with particular properties essential for hearing and that disruption of these heteromeric channels underlies the nonsyndromic nature of certain deafness-causing GJB2 mutations. </p><p><strong><em>Clouston Syndrome</em></strong></p><p>
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Lamartine et al. (2000) presented evidence that missense mutations in the GJB6 gene cause hidrotic ectodermal dysplasia (ECTD2; 129500), also known as Clouston syndrome. This disease is an autosomal dominant skin disorder characterized by palmoplantar hyperkeratosis, hair defects (from partial to total alopecia), nail hypoplasia, and nail deformities. Clouston syndrome had been mapped to the pericentromeric region of 13q, where the GJB2 and GJB6 genes are located. Involvement of GJB2 in Clouston syndrome was excluded by Kelsell et al. (1997). GJB6 seemed to be a good candidate for the disorder because hearing impairment had been reported in a few cases of Clouston syndrome. In addition, expression of GJB6 had been observed in mouse epidermis (Dahl et al., 1996), and Lamartine et al. (2000) detected a GJB6 transcript in human epidermal cells. They detected 2 missense mutations in the GJB6 gene: gly11 to arg (G11R; 604418.0002) and ala88 to val (A88V; 604418.0003). Affected individuals were heterozygous. </p><p>Common et al. (2002) transfected a keratinocyte cell line and HeLa cells with wildtype CX30 and CX30 mutants harboring disease-associated mutations. Mutations that result in skin disease, such as G11R (604418.0002) and A88V (604418.0003), impaired trafficking of the protein to the plasma membrane, thus preventing the formation of functional CX30 gap junctions. The deafness-associated mutation, T5M, resulted in correct trafficking of the protein to the membrane, but channel activity was impaired. </p><p>Essenfelder et al. (2004) analyzed the consequences of the G11R and A88V mutations on the functional properties of connexons. The distribution of CX30 was similar in affected palmoplantar skin and in normal epidermis. The presence of the wildtype protein improved trafficking of mutated CX30 to the plasma membrane where both G11R and A88V CX30 colocalized with wildtype CX30 and formed functional intercellular channels. Electrophysiologic properties of channels made of mutant CX30 differed slightly from those of wildtype CX30 but allowed for dye transfer between transfected HeLa cells. A gain of function was observed for G11R and A88V CX30, which formed functional hemichannels at the cell surface and, when expressed in HeLa cells, generated a leakage of ATP into the extracellular medium. Essenfelder et al. (2004) suggested that such increased ATP levels might act as a paracrine messenger that, by altering the epidermal factors that control proliferation and differentiation of keratinocytes, could play a role in the pathophysiologic processes leading to the Clouston syndrome phenotype. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Teubner et al. (2003) generated Gjb6-deficient mice by deletion of the Gjb6 coding region. Homozygous null mutants were born at the expected Mendelian frequency, developed normally, and were fertile; however, they exhibited a severe constitutive hearing impairment. From the age of hearing onset, these mice lacked the electrical potential difference between the endolymphatic and perilymphatic compartments of the cochlea (i.e., the endocochlear potential), which plays a key role in the high sensitivity of the mammalian auditory organ. In addition, after postnatal day 18, the cochlear sensory epithelium started to degenerate by cell apoptosis. Teubner et al. (2003) concluded that the Gjb6 null phenotype revealed a critical role of GJB6 both in generating the endocochlear potential and for survival of the auditory hair cells after the onset of hearing. </p><p>Using homologous recombination, Schutz et al. (2010) created a line of mice expressing human CX30 with the T5M substitution (604418.0001). Homozygous CX30-T5M mice were born at the expected mendelian ratio and were viable and fertile. In contrast to patients with a heterozygous T5M substitution, homozygous CX30-T5M mice showed only mild hearing impairment, with significantly increased hearing thresholds of about 15 decibels at all frequencies. In adult homozygous mice, CX30-T5M expression was reduced by approximately one-third compared with wildtype Cx30 levels, concomitant with downregulation of Cx26. CX30-T5M was expressed at cell membranes and formed gap junctions, and homozygous CX30-T5M mice showed normal endocochlear potentials. </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>ALLELIC VARIANTS</strong>
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</span>
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<strong>6 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 DEAFNESS, AUTOSOMAL DOMINANT 3B (1 family)</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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GJB6, THR5MET
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<br />
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SNP: rs104894414,
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gnomAD: rs104894414,
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ClinVar: RCV000088666
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</span>
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<div>
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<span class="mim-text-font">
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<p>In affected members of an Italian family with sensorineural hearing loss and linkage to chromosome 13q12 (DFNA3B; 612643), Grifa et al. (1999) identified a heterozygous C-to-T transition in the GJB6 gene, resulting in a thr5-to-met (T5M) substitution. In vitro functional expression studies in Xenopus oocytes showed that the mutant protein did not induce membrane potential coupling and suppressed the wildtype protein, consistent with a dominant-negative effect. The authors postulated that the negative inhibitory effect was due to direct interaction of intact and defective connexins at the plasma membrane level. </p><p>Using homologous recombination, Schutz et al. (2010) created a line of mice expressing human CX30 with the T5M substitution. Homozygous CX30-T5M mice were born at the expected mendelian ratio and were viable and fertile. In contrast to patients with a heterozygous T5M substitution, the homozygous CX30-T5M mice showed only mild hearing impairment, with significantly increased hearing thresholds of about 15 decibels at all frequencies. In adult homozygous mice, CX30-T5M expression was reduced by approximately one-third compared with wildtype Cx30 levels, concomitant with downregulation of Cx26. CX30-T5M was expressed at cell membranes and formed gap junctions, and homozygous CX30-T5M mice showed normal endocochlear potentials. </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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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 ECTODERMAL DYSPLASIA, HIDROTIC</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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GJB6, GLY11ARG
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<br />
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SNP: rs104894415,
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gnomAD: rs104894415,
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ClinVar: RCV000005882, RCV000255581, RCV000645727, RCV003335016
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 unrelated French families segregating a typical form of hidrotic ectodermal dysplasia (129500), Lamartine et al. (2000) found, in the GJB6 gene, a 31G-A transition leading to a gly11-to-arg (G11R) missense mutation. They analyzed 10 additional unrelated affected individuals of various geographic origins and found the same mutation in 1 African, 1 Spanish, 3 French-Canadian, 1 Scottish-Irish, and 1 additional French case. Three other patients had another missense mutation, ala88 to val (604418.0003). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 ECTODERMAL DYSPLASIA, HIDROTIC</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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GJB6, ALA88VAL
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<br />
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SNP: rs28937872,
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gnomAD: rs28937872,
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ClinVar: RCV000005883, RCV000798432, RCV002504751
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 3 patients with hidrotic ectodermal dysplasia (129500) originating from India, Malaysia, and Wales, Lamartine et al. (2000) found a 263C-T transition in the GJB6 gene leading to an ala88-to-val (A88V) missense mutation. </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 DEAFNESS, AUTOSOMAL RECESSIVE 1B</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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DEAFNESS, DIGENIC, GJB2/GJB6, INCLUDED
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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GJB6, 309-KB DEL
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<br />
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ClinVar: RCV000005884, RCV000005885, RCV000239454
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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 Spanish sibs with autosomal recessive deafness-1B (DFNB1B; 612645), del Castillo et al. (2002) identified homozygosity for a 342-kb deletion (342-KB DEL) in the GJB6 gene. The parents, who were deaf, were both found to be compound heterozygous for the GJB6 deletion and a common mutation in the GJB2 gene (35delG; 121011.0005), consistent with digenic inheritance (see 220290). A heterozygous GJB6 deletion was also identified in 22 of 33 additional Spanish patients with only 1 mutant GJB2 allele, again consistent with digenic inheritance due to compound heterozygous mutations in 2 different genes. Del Castillo et al. (2005) noted that the deletion size was 309 kb, according to more recent sequencing data. This deletion truncating the GJB6 gene was shown to be the accompanying mutation in approximately 50% of deaf GJB2 heterozygotes in a cohort of Spanish patients, thus becoming second only to 35delG at GJB2 as the most frequent mutation causing prelingual hearing impairment in Spain. </p><p>In a multicenter study in 9 countries, del Castillo et al. (2003) showed that the GJB6 deletion was present in most of the screening populations, with higher frequencies in France, Spain, and Israel where the percentages of unexplained GJB2 heterozygotes fell to 16 to 20.9% after screening for the GJB6 deletion mutation. Analysis of haplotypes associated with the deletion revealed a founder effect in Ashkenazi Jews and also suggested a common founder for countries in western Europe (the deletion mutation was referred to as del(GJB6-D13S1830) by del Castillo et al. (2003)). </p><p>Seeman et al. (2005) identified the 342-kb deletion in the GJB6 gene in 1 of 13 Czech patients with prelingual nonsyndromic sensorineural deafness who also carried 1 pathogenic mutation in the GJB2 gene. The deletion was not detected in 600 control chromosomes from Czech individuals with normal hearing. Seeman et al. (2005) concluded that the 342-kb deletion is very rare in central Europe compared to reports from Spain, France, and Israel. </p><p>In 324 probands with hearing loss and 280 controls, including 135 probands and 280 controls previously reported by Tang et al. (2006), Tang et al. (2008) screened for DNA sequence variations in GJB2 and for deletions in GJB6. The 232-kb GJB6 deletion (604418.0006) was not found, and the 309-kb GJB6 deletion was found only once, in a patient of unknown ethnicity who was also heterozygous for a truncating mutation in the GJB2 gene. Tang et al. (2008) suggested that the 232- and 309-kb deletions in the GJB6 gene may not be common in all populations. </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 ECTODERMAL DYSPLASIA 2, CLOUSTON TYPE</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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GJB6, VAL37GLU
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<br />
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SNP: rs104894416,
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gnomAD: rs104894416,
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ClinVar: RCV000005886
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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>Smith et al. (2002) reported a novel mutation, val37 to glu (V37E), within the first transmembrane domain of connexin-30 in a spontaneous case of Clouston syndrome (ECTD2; 129500). The amino acid substitution arose from a heterozygous 110T-to-A transversion in the GJB6 gene. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 DEAFNESS, DIGENIC, GJB2/GJB6</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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GJB6, 232-KB DEL
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<br />
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ClinVar: RCV000005887
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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 unrelated Spanish patients with autosomal recessive nonsyndromic hearing impairment who were heterozygous for 1 GJB2 (121011) mutant allele and did not carry the 309-kb GJB6 deletion (604418.0004), del Castillo et al. (2005) identified a 232-kb deletion, which they referred to as del(GJB6-D13S1854). The findings were consistent with digenic inheritance (see 220290). The 232-kb deletion was identified in trans in 12 of 47 unrelated affected Spanish individuals who were unresolved GJB2 heterozygotes. The deletion was not found in 100 control subjects with normal hearing. The 232-kb deletion was found to account for 22.2% of affected GJB2 heterozygotes who were unresolved after screening for the 309-kb deletion in the United Kingdom, for 6.3% in Brazil, and for 1.9% in northern Italy. By haplotype analysis, del Castillo et al. (2005) showed a common founder for the 232-kb deletion in Spain, the United Kingdom, and Italy. </p><p>In 324 probands with hearing loss and 280 controls, including 135 probands and 280 controls previously reported by Tang et al. (2006), Tang et al. (2008) screened for DNA sequence variations in GJB2 and for deletions in GJB6. The 232-kb GJB6 deletion was not found, and the 309-kb GJB6 deletion was found only once, in a patient of unknown ethnicity who was also heterozygous for a Q57X mutation in GJB2. Tang et al. (2008) suggested that the 232- and 309-kb deletions in the GJB6 gene may not be common in all populations. </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>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">
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Common, J. E. A., Becker, D., Di, W.-L., Leigh, I. M., O'Toole, E. A., Kelsell, D. P.
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<strong>Functional studies of human skin disease- and deafness-associated connexin 30 mutations.</strong>
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Biochem. Biophys. Res. Commun. 298: 651-656, 2002.
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[PubMed: 12419304]
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[Full Text: https://doi.org/10.1016/s0006-291x(02)02517-2]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Dahl, E., Manthey, D., Chen, Y., Schwarz, H. J., Chang, Y. S., Lalley, P. A., Nicholson, B. J., Willecke, K.
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<strong>Molecular cloning and functional expression of mouse connexin-30, a gap junction gene highly expressed in adult brain and skin.</strong>
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J. Biol. Chem. 271: 17903-17910, 1996. Note: Erratum: J. Biol. Chem. 271: 26444 only, 1996.
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[PubMed: 8663509]
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[Full Text: https://doi.org/10.1074/jbc.271.30.17903]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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del Castillo, F. J., Rodriguez-Ballesteros, M., Alvarez, A., Hutchin, T., Leonardi, E., de Oliveira, C. A., Azaiez, H., Brownstein, Z., Avenarius, M. R., Marlin, S., Pandya, A., Shahin, H., and 18 others.
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<strong>A novel deletion involving the connexin-30 gene, del(GJB6-d13s1854), found in trans with mutations in the GJB2 gene (connexin-26) in subjects with DFNB1 non-syndromic hearing impairment. (Letter)</strong>
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J. Med. Genet. 42: 588-594, 2005.
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[PubMed: 15994881]
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Marziano, N. K., Casalotti, S. O., Portelli, A. E., Becker, D. L., Forge, A.
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<strong>Mutations in the gene for connexin 26 (GJB2) that cause hearing loss have a dominant negative effect on connexin 30.</strong>
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Hum. Molec. Genet. 12: 805-812, 2003.
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Pallares-Ruiz, N., Blanchet, P., Mondain, M., Claustres, M., Roux, A.-F.
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<strong>A large deletion including most of GJB6 in recessive non syndromic deafness: a digenic effect?</strong>
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Europ. J. Hum. Genet. 10: 72-76, 2002.
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Schutz, M., Scimemi, P., Majumder, P., De Siati, R. D., Crispino, G., Rodriguez, L., Bortolozzi, M., Santarelli, R., Seydel, A., Sonntag, S., Ingham, N., Steel, K. P., Willecke, K., Mammano, F.
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<strong>The human deafness-associated connexin 30 T5M mutation causes mild hearing loss and reduces biochemical coupling among cochlear non-sensory cells in knock-in mice.</strong>
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Hum. Molec. Genet. 19: 4759-4773, 2010.
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Seeman, P., Bendova, O., Raskova, D., Malikova, M., Groh, D., Kabelka, Z.
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<strong>Double heterozygosity with mutations involving both the GJB2 and GJB6 genes is a possible, but very rare, cause of congenital deafness in the Czech population.</strong>
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Ann. Hum. Genet. 69: 9-14, 2005.
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[PubMed: 15638823]
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Smith, F. J. D., Morley, S. M., McLean, W. H. I.
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Tang, H.-Y., Basehore, M. J., Blakey, G. L., Darilek, S., Oghalai, J. S., Roa, B. B., Fang, P., Alford, R. L.
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<strong>Infrequency of two deletion mutations at the DFNB1 locus in patients and controls.</strong>
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Tang, H.-Y., Fang, P., Ward, P. A., Schmitt, E., Darilek, S., Manolidis, S., Oghalai, J. S., Roa, B. B., Alford, R. L.
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<strong>DNA sequence analysis of GJB2, encoding connexin 26: observations from a population of hearing impaired cases and variable carrier rates, complex genotypes, and ethnic stratification of alleles among controls.</strong>
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Am. J. Med. Genet. 140A: 2401-2415, 2006. Note: Erratum: Am. J. Med. Genet. 146A: 2979 only, 2008.
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Teubner, B., Michel, V., Pesch, J., Lautermann, J., Cohen-Salmon, M., Sohl, G., Jahnke, K., Winterhager, E., Herberhold, C., Hardelin, J.-P., Petit, C., Willecke, K.
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<strong>Connexin30 (Gjb6)-deficiency causes severe hearing impairment and lack of endocochlear potential.</strong>
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Hum. Molec. Genet. 12: 13-21, 2003.
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[PubMed: 12490528]
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<p>
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Thank you in advance for your generous support, <br />
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Ada Hamosh, MD, MPH <br />
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Scientific Director, OMIM <br />
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