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Entry
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- *118425 - CHLORIDE CHANNEL 1, SKELETAL MUSCLE; CLCN1
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*118425</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/118425">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000188037;t=ENST00000343257" 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=1180" 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=118425" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000188037;t=ENST00000343257" 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_000083,NR_046453" 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_000083" 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=118425" 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=00320&isoform_id=00320_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/CLCN1" 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/397143,398161,580290,6006523,6006527,41473247,51094531,85567593,109735129,119572243,119572244,311033468,1653961719" 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/P35523" 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=1180" 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=ENSG00000188037;t=ENST00000343257" 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=CLCN1" 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=CLCN1" 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+1180" 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/CLCN1" 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:1180" 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/1180" 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=chr7&hgg_gene=ENST00000343257.7&hgg_start=143316111&hgg_end=143352083&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://medlineplus.gov/genetics/gene/clcn1" 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=118425[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=118425[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/ENSG00000188037" 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=CLCN1" 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=CLCN1" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://www.LOVD.nl/CLCN1" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=CLCN1&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/PA26546" 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:2019" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0051116.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:88417" 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/CLCN1#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:88417" 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/1180/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA000698/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=1180" 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="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00000528;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00000528 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00000529;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00000529 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00000530;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00000530 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00000531;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00000531 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-060503-333" 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=CLCN1&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> 20305008, 57938005, 726051002, 8960007<br />
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<strong>ICD10CM:</strong> G71.12<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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118425
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
|
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<h3>
|
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<span class="mim-font">
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CHLORIDE CHANNEL 1, SKELETAL MUSCLE; CLCN1
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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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
CHLORIDE CHANNEL, MUSCLE; CLC1
|
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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=CLCN1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CLCN1</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>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/7/770?start=-3&limit=10&highlight=770">7q34</a>
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr7:143316111-143352083&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'})">7:143,316,111-143,352,083</a> </span>
|
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</em>
|
|
</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>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=160800,255700,160800" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/7/770?start=-3&limit=10&highlight=770">
|
|
7q34
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Myotonia congenita, dominant
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/160800"> 160800 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<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>
|
|
<span class="mim-font">
|
|
|
|
<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>
|
|
<td>
|
|
<span class="mim-font">
|
|
Myotonia congenita, recessive
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/255700"> 255700 </a>
|
|
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<p>The muscle chloride channel CLCN1 regulates the electric excitability of the skeletal muscle membrane. Skeletal muscle has an unusually high resting Cl(-) conductance and in vitro studies suggest that reduction of this conductance causes electrical instability and resulting myotonia in both humans and animal models. Muscle Cl(-) conductance is predominantly mediated by the CLCN1 chloride channel (summary by <a href="#38" class="mim-tip-reference" title="Steinmeyer, K., Lorenz, C., Pusch, M., Koch, M. C., Jentsch, T. J. <strong>Multimeric structure of ClC-1 chloride channel revealed by mutations in dominant myotonia congenita (Thomsen).</strong> EMBO J. 13: 737-743, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8112288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8112288</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1994.tb06315.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8112288">Steinmeyer et al., 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8112288" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By homology screening with the major rat skeletal muscle chloride channel CLCN1, <a href="#20" class="mim-tip-reference" title="Koch, M. C., Steinmeyer, K., Lorenz, C., Ricker, K., Wolf, F., Otto, M., Zoll, B., Lehmann-Horn, F., Grzeschik, K.-H., Jentsch, T. J. <strong>The skeletal muscle chloride channel in dominant and recessive human myotonia.</strong> Science 257: 797-800, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1379744/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1379744</a>] [<a href="https://doi.org/10.1126/science.1379744" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1379744">Koch et al. (1992)</a> cloned a partial human CLCN1 cDNA that covered about 80% of the coding sequence. This region was 88% identical to the rat channel in amino acid sequence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1379744" 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="Chen, T. T., Klassen, T. L., Goldman, A. M., Marini, C., Guerrini, R., Noebels, J. L. <strong>Novel brain expression of ClC-1 chloride channels and enrichment of CLCN1 variants in epilepsy.</strong> Neurology 80: 1078-1085, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23408874/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23408874</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23408874[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/10.1212/WNL.0b013e31828868e7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23408874">Chen et al. (2013)</a> found expression of the CLCN1 gene in various human brain regions, including cerebellum, hippocampus, spinal cord, and cerebral cortex, as well as in heart. Clcn1 was also expressed in the brain and heart of developing and adult mice. In mouse brain, neuronal expression of Clcn1 was detected in the pyramidal and dentate granule cells of the hippocampus, cerebellar Purkinje cells, scattered brainstem nuclei, frontal neocortex, and thalamus. The results suggested that CLCN1 has a role in neuronal function and excitability in addition to its known role in skeletal muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23408874" 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="#38" class="mim-tip-reference" title="Steinmeyer, K., Lorenz, C., Pusch, M., Koch, M. C., Jentsch, T. J. <strong>Multimeric structure of ClC-1 chloride channel revealed by mutations in dominant myotonia congenita (Thomsen).</strong> EMBO J. 13: 737-743, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8112288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8112288</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1994.tb06315.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8112288">Steinmeyer et al. (1994)</a> determined that CLCN1 functions as a homooligomer, most likely with 4 subunits. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8112288" 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="#32" class="mim-tip-reference" title="Pusch, M., Steinmeyer, K., Koch, M. C., Jentsch, T. J. <strong>Mutations in dominant human myotonia congenita drastically alter the voltage dependence of the CIC-1 chloride channel.</strong> Neuron 15: 1455-1463, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845168/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845168</a>] [<a href="https://doi.org/10.1016/0896-6273(95)90023-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845168">Pusch et al. (1995)</a> used a Xenopus transfection to demonstrate shifting of the gating of CLCN1 toward positive voltages by 4 different mutations identified in patients with myotonia congenita (<a href="/entry/160800">160800</a>). When these mutant cDNAs were coexpressed with wildtype subunits, they imposed altered voltage dependence on the heteromeric channels which would then open only in a voltage range where they could not contribute significantly to the repolarization of action potentials. Without such repolarizations, sodium channels have enough time to recover from inactivation leading to typical myotonic runs, which are a series of repetitive action potentials. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8845168" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#30" class="mim-tip-reference" title="Mindell, J. A., Maduke, M., Miller, C., Grigorieff, N. <strong>Projection structure of a CIC-type chloride channel at 6.5-angstrom resolution.</strong> Nature 409: 219-223, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11196649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11196649</a>] [<a href="https://doi.org/10.1038/35051631" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11196649">Mindell et al. (2001)</a> reported the formation of 2-dimensional crystals of the prokaryotic CLC channel homolog EriC reconstituted into phospholipid bilayer membranes. Cryoelectron microscopic analysis of these crystals yielded a projection structure at 6.5-angstrom resolution that showed off-axis water-filled pores within the dimeric channel complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11196649" 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>Crystal Structure</em></strong></p><p>
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<a href="#12" class="mim-tip-reference" title="Dutzler, R., Campbell, E. B., Cadene, M., Chait, B. T., MacKinnon, R. <strong>X-ray structure of a CIC chloride channel at 3.0 angstrom reveals the molecular basis of anion selectivity.</strong> Nature 415: 287-294, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11796999/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11796999</a>] [<a href="https://doi.org/10.1038/415287a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11796999">Dutzler et al. (2002)</a> presented the x-ray structures of 2 prokaryotic CLC chloride channels, from Salmonella typhimurium and E. coli, at 3.0 and 3.5 angstroms, respectively. Both structures revealed 2 identical pores, each pore being formed by a separate subunit contained within a homodimeric membrane protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11796999" 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 the 3-dimensional crystal structure of a bacterial CLC protein to predict residues involved in chloride channel inhibitor binding, <a href="#14" class="mim-tip-reference" title="Estevez, R., Schroeder, B. C., Accardi, A., Jentsch, T. J., Pusch, M. <strong>Conservation of chloride channel structure revealed by an inhibitor binding site in CIC-1.</strong> Neuron 38: 47-59, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12691663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12691663</a>] [<a href="https://doi.org/10.1016/s0896-6273(03)00168-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12691663">Estevez et al. (2003)</a> identified an inhibitor-binding site in human CLCN1. The binding site is localized close to the chloride-binding site and is accessible only from the intracellular side. <a href="#14" class="mim-tip-reference" title="Estevez, R., Schroeder, B. C., Accardi, A., Jentsch, T. J., Pusch, M. <strong>Conservation of chloride channel structure revealed by an inhibitor binding site in CIC-1.</strong> Neuron 38: 47-59, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12691663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12691663</a>] [<a href="https://doi.org/10.1016/s0896-6273(03)00168-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12691663">Estevez et al. (2003)</a> concluded that the structures of bacterial CLCs can be extrapolated with fidelity to mammalian chloride channels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12691663" 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="#25" class="mim-tip-reference" title="Lorenz, C., Meyer-Kleine, C., Steinmeyer, K., Koch, M. C., Jentsch, T. J. <strong>Genomic organization of the human muscle chloride channel CLC-1 and analysis of novel mutations leading to Becker-type myotonia.</strong> Hum. Molec. Genet. 3: 941-946, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951242/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951242</a>] [<a href="https://doi.org/10.1093/hmg/3.6.941" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7951242">Lorenz et al. (1994)</a> showed that the protein coding sequence of the CLCN1 gene is organized into 23 exons. Its upstream region contains a canonical TATA box, several consensus binding sites for myogenic transcription factors, and 2 other putative regulatory elements. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951242" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By blot hybridization to a panel of chromosome 7-specific, human-mouse somatic cell hybrids, <a href="#20" class="mim-tip-reference" title="Koch, M. C., Steinmeyer, K., Lorenz, C., Ricker, K., Wolf, F., Otto, M., Zoll, B., Lehmann-Horn, F., Grzeschik, K.-H., Jentsch, T. J. <strong>The skeletal muscle chloride channel in dominant and recessive human myotonia.</strong> Science 257: 797-800, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1379744/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1379744</a>] [<a href="https://doi.org/10.1126/science.1379744" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1379744">Koch et al. (1992)</a> mapped the CLCN1 gene to 7q32-qter. With RFLPs in the CLCN1 gene, they demonstrated that the locus is linked to the T-cell receptor beta locus (see <a href="/entry/186930">186930</a>) at 7q35 (maximum lod = 5.23 at theta = 0.0). In the mouse, it had previously been demonstrated that the corresponding loci are linked on chromosome 6, which shows other evidence of homology of synteny to human 7q (<a href="#37" class="mim-tip-reference" title="Steinmeyer, K., Klocke, R., Ortland, C., Gronemeier, M., Jockusch, H., Grunder, S., Jentsch, T. J. <strong>Inactivation of muscle chloride channel by transposon insertion in myotonic mice.</strong> Nature 354: 304-308, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1659665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1659665</a>] [<a href="https://doi.org/10.1038/354304a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1659665">Steinmeyer et al., 1991</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1659665+1379744" 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><strong><em>Myotonia Congenita</em></strong></p><p>
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In 3 brothers, born of consanguineous parents, with autosomal recessive myotonia congenita (Becker disease; <a href="/entry/255700">255700</a>), <a href="#20" class="mim-tip-reference" title="Koch, M. C., Steinmeyer, K., Lorenz, C., Ricker, K., Wolf, F., Otto, M., Zoll, B., Lehmann-Horn, F., Grzeschik, K.-H., Jentsch, T. J. <strong>The skeletal muscle chloride channel in dominant and recessive human myotonia.</strong> Science 257: 797-800, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1379744/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1379744</a>] [<a href="https://doi.org/10.1126/science.1379744" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1379744">Koch et al. (1992)</a> identified a homozygous mutation in the CLCN1 gene (F413C; <a href="#0001">118425.0001</a>). In affected members of 3 unrelated families with autosomal dominant myotonia congenita (Thomsen disease; <a href="/entry/160800">160800</a>), <a href="#16" class="mim-tip-reference" title="George, A. L., Jr., Crackower, M. A., Abdalla, J. A., Hudson, A. J., Ebers, G. C. <strong>Molecular basis of Thomsen's disease (autosomal dominant myotonia congenita).</strong> Nature Genet. 3: 305-310, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7981750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7981750</a>] [<a href="https://doi.org/10.1038/ng0493-305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7981750">George et al. (1993)</a> identified a heterozygous mutation in the CLCN1 gene (G230E; <a href="#0002">118425.0002</a>). The findings indicated that the 2 disorders are allelic. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7981750+1379744" 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="#29" class="mim-tip-reference" title="Meyer-Kleine, C., Steinmeyer, K., Ricker, K., Jentsch, T. J., Koch, M. C. <strong>Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCN1) leading to myotonia.</strong> Am. J. Hum. Genet. 57: 1325-1334, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8533761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8533761</a>]" pmid="8533761">Meyer-Kleine et al. (1995)</a> identified 15 different mutations in the CLCN1 gene, of which 10 were novel, in a total of 17 unrelated families and 13 single patients with Becker-type myotonia congenita. One additional family had the dominant Thomsen form. Three mutations accounted for 32% of the Becker chromosomes in the German population; F413C, R894X (<a href="#0015">118425.0015</a>), and a 14-bp deletion in exon 13 (<a href="#0009">118425.0009</a>). Although a 437A-T transversion had been described as a disease-causing mutation (<a href="#21" class="mim-tip-reference" title="Koty, P. P., Marks, H. G., Turel, A., Flagler, D., Angelini, C., Pegoraro, E., Vancott, A. C., Manchester, D., Zonana, J., Bird, T. D., Hoffman, E. P. <strong>Linkage analysis of Thomsen and Becker myotonia families. (Abstract)</strong> Am. J. Hum. Genet. 55 (suppl.): A227, 1994."None>Koty et al., 1994</a>), <a href="#29" class="mim-tip-reference" title="Meyer-Kleine, C., Steinmeyer, K., Ricker, K., Jentsch, T. J., Koch, M. C. <strong>Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCN1) leading to myotonia.</strong> Am. J. Hum. Genet. 57: 1325-1334, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8533761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8533761</a>]" pmid="8533761">Meyer-Kleine et al. (1995)</a> observed it in 3 myotonia families and in 5 of 200 control chromosomes, consistent with a polymorphism. Moreover, mutant 437A-T cRNA was functionally expressed in Xenopus oocytes and found to induce currents that were indistinguishable from wildtype currents. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8533761" 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 screening of 6 unrelated patients with recessive Becker-type myotonia, <a href="#26" class="mim-tip-reference" title="Mailander, V., Heine, R., Deymeer, F., Lehmann-Horn, F. <strong>Novel muscle chloride channel mutations and their effects on heterozygous carriers.</strong> Am. J. Hum. Genet. 58: 317-324, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8571958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8571958</a>]" pmid="8571958">Mailander et al. (1996)</a> identified 4 novel CLCN1 mutations and a previously reported 14-bp deletion. Five patients were homozygous and the sixth patient was compound heterozygous. Heterozygous carriers of the Becker mutation did not display any clinical symptoms of myotonia; however, all heterozygous males, but none of the heterozygous females, exhibited myotonic discharges on EMG, suggesting a gene-dosage effect of the mutations on chloride conductance and a male predominance of subclinical myotonia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8571958" 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="#44" class="mim-tip-reference" title="Wollnik, B., Kubisch, C., Steinmeyer, K., Pusch, M. <strong>Identification of functionally important regions of the muscular chloride channel CIC-1 by analysis of recessive and dominant myotonic mutations.</strong> Hum. Molec. Genet. 6: 805-811, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9158157/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9158157</a>] [<a href="https://doi.org/10.1093/hmg/6.5.805" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9158157">Wollnik et al. (1997)</a> analyzed the effect of 1 dominant and 3 recessive mutations in the CLCN1 gene after functional expression in Xenopus oocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9158157" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Esteban, J., Neumeyer, A. M., McKenna-Yasek, D., Brown, R. H. <strong>Identification of two mutations and a polymorphism in the chloride channel CLCN-1 in patients with Becker's generalized myotonia.</strong> Neurogenetics 1: 185-188, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10737121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10737121</a>] [<a href="https://doi.org/10.1007/s100480050027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10737121">Esteban et al. (1998)</a> stated that 31 specific mutations in the CLCN1 gene had been related to myotonia congenita in humans and 3 in mice. They described a homozygous arg317-to-gln (R317Q; <a href="#0011">118425.0011</a>) mutation in affected members of a family with autosomal recessive myotonia congenita. A heterozygous brother had mild muscle stiffness consistent with latent myotonia. The parents were unaffected, although only the mother, who was heterozygous, was available for DNA study. The same R317Q mutation had previously been identified in a family with dominant Thomsen myotonia congenita. At least 2 other mutations, G230E (<a href="#0002">118425.0002</a>) and R894X, had been found in both dominant and recessive myotonia congenita, depending on the particular family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10737121" 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="#22" class="mim-tip-reference" title="Kubisch, C., Schmidt-Rose, T., Fontaine, B., Bretag, A. H., Jentsch, T. J. <strong>ClC-1 chloride channel mutations in myotonia congenita: variable penetrance of mutations shifting the voltage dependence.</strong> Hum. Molec. Genet. 7: 1753-1760, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9736777/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9736777</a>] [<a href="https://doi.org/10.1093/hmg/7.11.1753" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9736777">Kubisch et al. (1998)</a> identified 4 novel missense mutations in the CLCN gene, 2 in the dominant form and 2 in the recessive form of myotonia. The first 2 displayed a classic dominant phenotype with a dominant-negative effect by significantly imparting a voltage shift on mutant/wildtype heteromeric channels as found in heterozygous patients. One of the recessive mutations also shifted the voltage dependence to positive values, but coexpression with wildtype CLCN1 gave almost wildtype currents. The voltage dependence of mutant heteromeric channels was not always intermediate between those of the constituent homomeric channel subunits. These complex interactions correlated clinically with various inheritance patterns, ranging from autosomal dominant with various degrees of penetrance to autosomal recessive. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9736777" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of 18 unrelated families from Norway and Sweden with both autosomal dominant (5 families) and autosomal recessive (13 families) inheritance of myotonia congenita, <a href="#40" class="mim-tip-reference" title="Sun, C., Tranebjaerg, L., Torbergsen, T., Holmgren, G., Van Ghelue, M. <strong>Spectrum of CLCN1 mutations in patients with myotonia congenita in northern Scandinavia.</strong> Europ. J. Hum. Genet. 9: 903-909, 2001. Note: Erratum: Europ. J. Hum. Genet. 18: 264 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11840191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11840191</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200736" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11840191">Sun et al. (2001)</a> identified 8 different mutations (1 nonsense, 4 missense, and 3 splice mutations) in the CLCN1 gene; 3 mutations were novel. Fifteen patients had mutations on both alleles, consistent with the recessive disorder; 2 probands had mutations in a single allele; and 2 probands had no CLCN1 mutations. In 2 families, 3 CLCN1 mutations were found in the proband, and <a href="#40" class="mim-tip-reference" title="Sun, C., Tranebjaerg, L., Torbergsen, T., Holmgren, G., Van Ghelue, M. <strong>Spectrum of CLCN1 mutations in patients with myotonia congenita in northern Scandinavia.</strong> Europ. J. Hum. Genet. 9: 903-909, 2001. Note: Erratum: Europ. J. Hum. Genet. 18: 264 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11840191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11840191</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200736" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11840191">Sun et al. (2001)</a> suspected that this phenomenon may be underestimated because mutation search in a disease gene usually ends by the identification of 2 mutations in a family with recessive inheritance. Families with apparently dominant segregation of myotonia congenita may actually represent recessive inheritance with undetected heterozygous individuals married-in as a consequence of a high population carrier frequency of some mutations. The findings, together with the very variable clinical presentation, challenged the classification into dominant Thomsen or recessive Becker disease. <a href="#40" class="mim-tip-reference" title="Sun, C., Tranebjaerg, L., Torbergsen, T., Holmgren, G., Van Ghelue, M. <strong>Spectrum of CLCN1 mutations in patients with myotonia congenita in northern Scandinavia.</strong> Europ. J. Hum. Genet. 9: 903-909, 2001. Note: Erratum: Europ. J. Hum. Genet. 18: 264 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11840191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11840191</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200736" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11840191">Sun et al. (2001)</a> suggested that most cases of myotonia congenita show recessive inheritance with some modifying factors or genetic heterogeneity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11840191" 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 review, <a href="#33" class="mim-tip-reference" title="Pusch, M. <strong>Myotonia caused by mutations in the muscle chloride channel gene CLCN1.</strong> Hum. Mutat. 19: 423-434, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11933197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11933197</a>] [<a href="https://doi.org/10.1002/humu.10063" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11933197">Pusch (2002)</a> stated that more than 60 CLCN1 mutations had been identified as causing myotonia, with only a few of them being dominant. A dominant-negative effect of mutant subunits in mutant-wildtype heterodimers was suggested as the usual mechanism for dominant mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11933197" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Duno, M., Colding-Jorgensen, E., Grunnet, M., Jespersen, T., Vissing, J., Schwartz, M. <strong>Difference in allelic expression of the CLCN1 gene and the possible influence on the myotonia congenita phenotype.</strong> Europ. J. Hum. Genet. 12: 738-743, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15162127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15162127</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201218" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15162127">Duno et al. (2004)</a> reported 4 unrelated families with myotonia congenita and the R894X mutation: 2 families had a single mutant allele, showing dominant inheritance, and 2 families were compound heterozygous for R894X and another mutation, showing recessive inheritance. RT-PCR did not reveal any association between total CLCN1 mRNA in muscle and the mode of inheritance, but the dominant family with the most severe phenotype expressed twice the expected amount of the R894X mRNA allele, even compared to the recessive families. <a href="#10" class="mim-tip-reference" title="Duno, M., Colding-Jorgensen, E., Grunnet, M., Jespersen, T., Vissing, J., Schwartz, M. <strong>Difference in allelic expression of the CLCN1 gene and the possible influence on the myotonia congenita phenotype.</strong> Europ. J. Hum. Genet. 12: 738-743, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15162127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15162127</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201218" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15162127">Duno et al. (2004)</a> suggested that variation in allelic expression may be a modifier of disease expression and progression in myotonia congenita. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15162127" 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="#34" class="mim-tip-reference" title="Raja Rayan, D. L., Haworth, A., Sud, R., Matthews, E., Fialho, D., Burge, J., Portaro, S., Schorge, S., Tuin, K., Lunt, P., McEntagart, M., Toscano, A., Davis, M. B., Hanna, M. G. <strong>A new explanation for recessive myotonia congenita: exon deletions and duplications in CLCN1.</strong> Neurology 78: 1953-1958, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22649220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22649220</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22649220[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/10.1212/WNL.0b013e318259e19c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22649220">Raja Rayan et al. (2012)</a> performed multiplex ligation-dependent probe amplification (MLPA) specific to the CLCN1 gene in 60 families with recessive myotonia congenita in whom either no mutations or only a single pathogenic CLCN1 mutation had been identified. The results were positive in 4 (6.7%) patients: 2 unrelated patients were found to have 2 different multiexon deletions within the CLCN1 gene on the second allele, and 2 additional patients had a homozygous duplication of exons 8 through 14 of the CLCN1 gene (<a href="#0020">118425.0020</a>). The 2 patients with the duplication were both of Iraqi origin, but were unrelated. Both Iraqi patients had a severe form of the disorder with onset in infancy. Haplotype analysis suggested a founder effect for this duplication mutation. <a href="#34" class="mim-tip-reference" title="Raja Rayan, D. L., Haworth, A., Sud, R., Matthews, E., Fialho, D., Burge, J., Portaro, S., Schorge, S., Tuin, K., Lunt, P., McEntagart, M., Toscano, A., Davis, M. B., Hanna, M. G. <strong>A new explanation for recessive myotonia congenita: exon deletions and duplications in CLCN1.</strong> Neurology 78: 1953-1958, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22649220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22649220</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22649220[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/10.1212/WNL.0b013e318259e19c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22649220">Raja Rayan et al. (2012)</a> concluded that copy number variation involving the CLCN1 gene is an important genetic mechanism in patients with recessive myotonia congenita, and that MLPA analysis may aid in genetic counseling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22649220" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 4 Costa Rican families with myotonia congenita, <a href="#43" class="mim-tip-reference" title="Vindas-Smith, R., Fiore, M., Vasquez, M., Cuenca, P., del Valle, G., Lagostena, L., Gaitan-Penas, H., Estevez, R., Pusch, M., Morales, F. <strong>Identification and functional characterization of CLCN1 mutations found in nondystrophic myotonia patients.</strong> Hum. Mutat. 37: 74-83, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26510092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26510092</a>] [<a href="https://doi.org/10.1002/humu.22916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26510092">Vindas-Smith et al. (2016)</a> identified mutations in the CLCN1 gene by bidirectional sequencing of the CLCN1 gene, with confirmation by RFLP-PCR. In 2 families in which the proband had Thomsen disease (families 1 and 4), heterozygous mutations were identified (F167L; Q412P, <a href="#0022">118425.0022</a>). In another family in which the proband had Thomsen disease (family 2), compound heterozygous mutations were identified (R105C and F167L). In a proband (family 3) with a myositis-like disorder, a variant of unknown significance (Q154R) was identified. Functional studies of CLCN1 with the F167L, R105C, or Q154R mutation did not show alterations of gating parameters or channel conductance. Functional studies of CLCN1 with the Q412P mutation expressed in Xenopus oocytes showed reduced surface expression and reduced current density. <a href="#43" class="mim-tip-reference" title="Vindas-Smith, R., Fiore, M., Vasquez, M., Cuenca, P., del Valle, G., Lagostena, L., Gaitan-Penas, H., Estevez, R., Pusch, M., Morales, F. <strong>Identification and functional characterization of CLCN1 mutations found in nondystrophic myotonia patients.</strong> Hum. Mutat. 37: 74-83, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26510092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26510092</a>] [<a href="https://doi.org/10.1002/humu.22916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26510092">Vindas-Smith et al. (2016)</a> concluded that the Q412P mutation induces a severe folding defect that leads to its degradation before it can dimerize with the wildtype subunit. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26510092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Altamura, C., Lucchiari, S., Sahbani, D., Ulzi, G., Comi, G. P., D'Ambrosio, P., Petillo, R., Politano, L., Vercelli, L., Mongini, T., Dotti, M. T., Cardani, R., Meola, G., Lo Monaco, M., Matthews, E., Hanna, M. G., Carratu, M. R., Conte, D., Imbrici, P., Desaphy, J.-F. <strong>The analysis of myotonia congenita mutations discloses functional clusters of amino acids within the CBS2 domain and the C-terminal peptide of the CLC-1 channel.</strong> Hum. Mutat. 39: 1273-1283, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29935101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29935101</a>] [<a href="https://doi.org/10.1002/humu.23581" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29935101">Altamura et al. (2018)</a> evaluated the functional significance of 7 mutations in the C-terminal region of the CLCN1 gene associated with either autosomal dominant Thomsen disease or autosomal recessive Becker disease. CLCN1 with each mutation was transfected into HEK293 cells and analyzed with patch-clamp analysis. Five of the mutations were in the CBS2 domain (V829M, T832I, V851M, G859V, L861P) and 2 of the mutations were in the C-terminal peptide (P883T, V947E). Mutations located between residues 829 and 835 and in residue 883 resulted in alteration of voltage dependence. Mutations between residues 851 and 859 and in residue 947 resulted in a reduction of chloride currents. The results were consistent with a role for CBS2 in protein channel gating and demonstrated the importance of the C-peptide region in protein function and expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29935101" 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="#39" class="mim-tip-reference" title="Suetterlin, K., Matthews, E., Sud, R., McCall, S., Fialho, D., Burge, J., Jayaseelan, D., Haworth, A., Sweeney, M. G., Kullmann, D. M., Schorge, S., Hanna, M. G., Mannikko, R. <strong>Translating genetic and functional data into clinical practice: a series of 223 families with myotonia.</strong> Brain 145: 607-620, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34529042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34529042</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34529042[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/brain/awab344" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34529042">Suetterlin et al. (2022)</a> assessed the function of 95 CLCN1 mutations, including 34 novel mutations, identified in 233 patients with myotonia congenita. Mutations in CLCN1 were assessed by transfection of cDNA with each mutation into Xenopus laevis oocytes and analyzed with 2-electrode voltage clamp assays. From a functional standpoint, mutations that altered voltage dependence of activation clustered in the first half of the transmembrane domains and mutations resulting in absent currents clustered in the second half of the transmembrane domain. In terms of assessment of clinical significance and inheritance patterns, mutations that resulted in dominant functional features clustered in the TM1 domain, and variants associated with recessive functional features and without a shift in voltage dependence of activation were clustered in the TM2 domain. Mutations in the intracellular domain were not associated with a dominant inheritance pattern. <a href="#39" class="mim-tip-reference" title="Suetterlin, K., Matthews, E., Sud, R., McCall, S., Fialho, D., Burge, J., Jayaseelan, D., Haworth, A., Sweeney, M. G., Kullmann, D. M., Schorge, S., Hanna, M. G., Mannikko, R. <strong>Translating genetic and functional data into clinical practice: a series of 223 families with myotonia.</strong> Brain 145: 607-620, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34529042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34529042</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34529042[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/brain/awab344" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34529042">Suetterlin et al. (2022)</a> concluded that functional characterization of CLCN1 mutations improves the assessment of their clinical implications. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34529042" 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>Myotonic Dystrophy</em></strong></p><p>
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Myotonic dystrophy (DM1; <a href="/entry/160900">160900</a>) is caused by a trinucleotide repeat expansion of the DMPK gene (<a href="/entry/605377#0001">605377.0001</a>). In DM, expression of RNAs that contain expanded CUG or CCUG repeats is associated with degeneration and repetitive action potentials (myotonia) in skeletal muscle. Using skeletal muscle from a transgenic mouse model of DM, <a href="#27" class="mim-tip-reference" title="Mankodi, A., Takahashi, M. P., Jiang, H., Beck, C. L., Bowers, W. J., Moxley, R. T., Cannon, S. C., Thornton, C. A. <strong>Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy.</strong> Molec. Cell 10: 35-44, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12150905/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12150905</a>] [<a href="https://doi.org/10.1016/s1097-2765(02)00563-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12150905">Mankodi et al. (2002)</a> showed that expression of expanded CUG repeats reduced the transmembrane chloride conductance to levels well below those expected to cause myotonia. The expanded CUG repeats triggered aberrant splicing of pre-mRNA for CLCN1, resulting in loss of the CLCN1 protein from the surface membrane. <a href="#27" class="mim-tip-reference" title="Mankodi, A., Takahashi, M. P., Jiang, H., Beck, C. L., Bowers, W. J., Moxley, R. T., Cannon, S. C., Thornton, C. A. <strong>Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy.</strong> Molec. Cell 10: 35-44, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12150905/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12150905</a>] [<a href="https://doi.org/10.1016/s1097-2765(02)00563-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12150905">Mankodi et al. (2002)</a> identified a similar defect in CLCN1 splicing and expression in DM1 and DM2 (<a href="/entry/602668">602668</a>). The authors proposed that a transdominant effect of mutant RNA on CLCN1 RNA processing leads to chloride channelopathy and membrane hyperexcitability in DM. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12150905" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Charlet-B, N., Savkur, R. S., Singh, G., Philips, A. V., Grice, E. A., Cooper, T. A. <strong>Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing.</strong> Molec. Cell 10: 45-53, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12150906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12150906</a>] [<a href="https://doi.org/10.1016/s1097-2765(02)00572-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12150906">Charlet-B et al. (2002)</a> demonstrated loss of CLCN1 mRNA and protein in DM1 skeletal muscle tissue due to aberrant splicing of the CLCN1 pre-mRNA. They showed that the splicing regulator, CUG-binding protein (CUGBP; <a href="/entry/601074">601074</a>), which is elevated in DM1 striated muscle, bound to the CLCN1 pre-mRNA, and that overexpression of CUGBP in normal cells reproduced the aberrant pattern of CLCN1 splicing observed in DM1 skeletal muscle. <a href="#7" class="mim-tip-reference" title="Charlet-B, N., Savkur, R. S., Singh, G., Philips, A. V., Grice, E. A., Cooper, T. A. <strong>Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing.</strong> Molec. Cell 10: 45-53, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12150906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12150906</a>] [<a href="https://doi.org/10.1016/s1097-2765(02)00572-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12150906">Charlet-B et al. (2002)</a> proposed that disruption of alternative splicing regulation causes a predominant pathologic feature of DM1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12150906" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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See <a href="#0021">118425.0021</a> for discussion of a possible association between variation in the CLCN1 gene and idiopathic generalized epilepsy (EIG; see <a href="/entry/600669">600669</a>).</p>
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<p><a href="#3" class="mim-tip-reference" title="Aminoff, M. J., Layzer, R. B., Satya-Murti, S., Faden, A. I. <strong>The declining electrical response of muscle to repetitive nerve stimulation in myotonia.</strong> Neurology 27: 812-816, 1977.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/561337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">561337</a>] [<a href="https://doi.org/10.1212/wnl.27.9.812" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="561337">Aminoff et al. (1977)</a> found that a subset of patients with myotonia congenita showed a marked decrement of the compound motor action potential (CMAP) with repeated stimulation compared to controls. Although the presence of decrement was not related to the degree of myotonia, it was usually observed in patients with autosomal recessive disease. <a href="#9" class="mim-tip-reference" title="Colding-Jorgensen, E., Duno, M., Schwartz, M., Vissing, J. <strong>Decrement of compound muscle action potential is related to mutation type in myotonia congenita.</strong> Muscle Nerve 27: 449-455, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12661046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12661046</a>] [<a href="https://doi.org/10.1002/mus.10347" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12661046">Colding-Jorgensen et al. (2003)</a> found that all 6 patients with the dominant P480L (<a href="#0006">118425.0006</a>) mutation had CMAP decrements above 30%. In patients with the R894X (<a href="#0015">118425.0015</a>) mutation, some had a large decrement, some had a slight decrement, and some had no change. Two patients with 2 CLCN1 mutations, 1 of whom carried an R894X mutation, had large decrements above 80%. Presence of decrement did not correlate with disease severity. <a href="#9" class="mim-tip-reference" title="Colding-Jorgensen, E., Duno, M., Schwartz, M., Vissing, J. <strong>Decrement of compound muscle action potential is related to mutation type in myotonia congenita.</strong> Muscle Nerve 27: 449-455, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12661046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12661046</a>] [<a href="https://doi.org/10.1002/mus.10347" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12661046">Colding-Jorgensen et al. (2003)</a> concluded that CMAP decrement may occur in dominant myotonia congenita and likely reflects the degree of chloride conduction reduction caused by particular mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=561337+12661046" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The Adr ('arrested development of righting') mouse, a model of autosomal recessive myotonia congenita, was found to be due to a mutation on mouse chromosome 6 (<a href="#35" class="mim-tip-reference" title="Rudel, R. <strong>The myotonic mouse--a realistic model for the study of human recessive generalized myotonia.</strong> Trends Neurosci. 13: 1-3, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1688667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1688667</a>] [<a href="https://doi.org/10.1016/0166-2236(90)90049-g" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1688667">Rudel, 1990</a>) in a region of the genome with homology of synteny to human chromosome 7q31-q35. The locus in the mouse is between those for Tcrb and Hox1. <a href="#37" class="mim-tip-reference" title="Steinmeyer, K., Klocke, R., Ortland, C., Gronemeier, M., Jockusch, H., Grunder, S., Jentsch, T. J. <strong>Inactivation of muscle chloride channel by transposon insertion in myotonic mice.</strong> Nature 354: 304-308, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1659665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1659665</a>] [<a href="https://doi.org/10.1038/354304a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1659665">Steinmeyer et al. (1991)</a> found that the Adr mouse phenotype was caused by a transposon insertion mutation that altered and inactivated the muscle-membrane chloride channel gene. The findings confirmed that the Adr mouse is an authentic model of Becker disease in the human. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1688667+1659665" 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="#45" class="mim-tip-reference" title="Wu, H., Olson, E. N. <strong>Activation of the MEF2 transcription factor in skeletal muscles from myotonic mice.</strong> J. Clin. Invest. 109: 1327-1333, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12021248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12021248</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12021248[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/10.1172/JCI15417" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12021248">Wu and Olson (2002)</a> determined that Adr mice, which have an inactivated Clcn1 gene, showed an increased number of oxidative fibers, lacked glycolytic fibers, and showed muscle hypertrophy, similar to patients with Becker syndrome. By breeding Clcn1-null mice with mice harboring an Mef2 (<a href="/entry/600660">600660</a>)-dependent reporter gene, they found that the transcriptional activity of Mef2 was dramatically enhanced in myotonic muscle. Induction of Mef2 did not correlate with enhanced DNA-binding activity, but did correlate with activation of p38 Mapk (see <a href="/entry/600289">600289</a>), an activator of Mef2, and with reduced expression of class II histone deacetylases (HDACs; see <a href="/entry/605314">605314</a>), which repress Mef2 activity. <a href="#45" class="mim-tip-reference" title="Wu, H., Olson, E. N. <strong>Activation of the MEF2 transcription factor in skeletal muscles from myotonic mice.</strong> J. Clin. Invest. 109: 1327-1333, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12021248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12021248</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12021248[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/10.1172/JCI15417" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12021248">Wu and Olson (2002)</a> hypothesized that mutations in Clcn1 alter intracellular calcium levels, leading to the combined effects of class II Hdac deficiency and p38 Mapk activation, resulting in upregulation of Mef2 transcriptional activity followed by long-term changes in gene expression and to fiber-type transformation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12021248" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Beck, C. L., Fahlke, C., George, A. L., Jr. <strong>Molecular basis for decreased muscle chloride conductance in the myotonic goat.</strong> Proc. Nat. Acad. Sci. 93: 11248-11252, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8855341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8855341</a>] [<a href="https://doi.org/10.1073/pnas.93.20.11248" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8855341">Beck et al. (1996)</a> noted that the current hypotheses regarding the pathophysiology of autosomal dominant myotonia congenita, or Thomsen disease, were initially formulated from studies of the myotonic goat, an unusual breed afflicted with severe autosomal dominant congenital myotonia that closely resembles the human disease clinically and in its mode of inheritance. These animals are often referred to as 'fainting,' 'nervous,' 'stiff-legged,' or 'epileptic' goats because of their tendency to develop severe acute muscle stiffness and become immobile and often fall when attempting to make sudden forceful movements or when startled. The pathogenesis of myotonia in the goat was elucidated by Bryant and colleagues (<a href="#6" class="mim-tip-reference" title="Bryant, S. H. <strong>Muscle membrane of normal and myotonic goats in normal and low external chloride. (Abstract)</strong> Fed. Proc. 21: 312 only, 1962."None>Bryant, 1962</a>, <a href="#24" class="mim-tip-reference" title="Lipicky, R. J., Bryant, S. H. <strong>Sodium, potassium, and chloride fluxes in intercostal muscle from normal goats and goats with hereditary myotonia.</strong> J. Gen. Physiol. 50: 89-111, 1966.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5971035/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5971035</a>] [<a href="https://doi.org/10.1085/jgp.50.1.89" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5971035">Lipicky and Bryant, 1966</a>) who first described a severely diminished resting chloride conductance in muscle fibers from affected animals. The same group (<a href="#1" class="mim-tip-reference" title="Adrian, R. H., Bryant, S. H. <strong>On the repetitive discharge in myotonic muscle fibres.</strong> J. Physiol. 240: 505-515, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4420758/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4420758</a>] [<a href="https://doi.org/10.1113/jphysiol.1974.sp010620" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4420758">Adrian and Bryant, 1974</a>) also demonstrated that myotonia could be produced in normal skeletal muscle fibers bathed in a chloride-free solution. <a href="#4" class="mim-tip-reference" title="Beck, C. L., Fahlke, C., George, A. L., Jr. <strong>Molecular basis for decreased muscle chloride conductance in the myotonic goat.</strong> Proc. Nat. Acad. Sci. 93: 11248-11252, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8855341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8855341</a>] [<a href="https://doi.org/10.1073/pnas.93.20.11248" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8855341">Beck et al. (1996)</a> demonstrated the molecular basis for the decreased muscle chloride conductance in this historically important animal model. They found a single nucleotide change (GCC to CCC), resulting in an ala885-to-pro (A885P) substitution in a conserved residue in the C terminus of the goat muscle chloride channel, 104 residues from the termination codon. Heterologous expression of the mutation demonstrated a substantial (+47 mV) shift in the midpoint of steady-state activation of the channel, resulting in a diminished channel open probability at voltages near the resting membrane potential of skeletal muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8855341+4420758+5971035" 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>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>22 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=118425[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<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> rs121912799 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912799;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/rs121912799?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=rs121912799" 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=rs121912799" 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=RCV000019083 OR RCV000184008 OR RCV000346725 OR RCV000638232 OR RCV001548747 OR RCV002291268" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019083, RCV000184008, RCV000346725, RCV000638232, RCV001548747, RCV002291268" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019083...</a>
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<p>In 3 brothers with autosomal recessive generalized myotonia congenita (Becker disease; <a href="/entry/255700">255700</a>), born of consanguineous parents, <a href="#20" class="mim-tip-reference" title="Koch, M. C., Steinmeyer, K., Lorenz, C., Ricker, K., Wolf, F., Otto, M., Zoll, B., Lehmann-Horn, F., Grzeschik, K.-H., Jentsch, T. J. <strong>The skeletal muscle chloride channel in dominant and recessive human myotonia.</strong> Science 257: 797-800, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1379744/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1379744</a>] [<a href="https://doi.org/10.1126/science.1379744" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1379744">Koch et al. (1992)</a> identified a homozygous T-to-G transversion in the CLCN1 gene, resulting in a phe413-to-cys (F413C) substitution toward the end of putative membrane span D8. This residue lies in a highly conserved region of the channel protein that is predicted to form a membrane-spanning alpha helix and possibly a component of the permeation pore (<a href="#16" class="mim-tip-reference" title="George, A. L., Jr., Crackower, M. A., Abdalla, J. A., Hudson, A. J., Ebers, G. C. <strong>Molecular basis of Thomsen's disease (autosomal dominant myotonia congenita).</strong> Nature Genet. 3: 305-310, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7981750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7981750</a>] [<a href="https://doi.org/10.1038/ng0493-305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7981750">George et al., 1993</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7981750+1379744" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Koch, M. C., Ricker, K., Otto, M., Wolf, F., Zoll, B., Lorenz, C., Steinmeyer, K., Jentsch, T. J. <strong>Evidence for genetic homogeneity in autosomal recessive generalised myotonia (Becker).</strong> J. Med. Genet. 30: 914-917, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8301644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8301644</a>] [<a href="https://doi.org/10.1136/jmg.30.11.914" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8301644">Koch et al. (1993)</a> found the F413C missense mutation in 15% of chromosomes carrying a gene for recessive myotonia congenita. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8301644" 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> rs80356700 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356700;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/rs80356700?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=rs80356700" 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=rs80356700" 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=RCV000019084 OR RCV000020113 OR RCV000291823 OR RCV000627758 OR RCV003317041 OR RCV004532391" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019084, RCV000020113, RCV000291823, RCV000627758, RCV003317041, RCV004532391" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019084...</a>
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<p>In affected members of 3 unrelated families with autosomal dominant myotonia congenita (Thomsen disease; <a href="/entry/160800">160800</a>), <a href="#16" class="mim-tip-reference" title="George, A. L., Jr., Crackower, M. A., Abdalla, J. A., Hudson, A. J., Ebers, G. C. <strong>Molecular basis of Thomsen's disease (autosomal dominant myotonia congenita).</strong> Nature Genet. 3: 305-310, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7981750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7981750</a>] [<a href="https://doi.org/10.1038/ng0493-305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7981750">George et al. (1993)</a> identified a G-to-A transition in the CLCN1 gene, resulting in a gly230-to-glu (G230E) substitution between the third and fourth predicted membrane-spanning segments. This glycine residue is conserved in all known members of this class of chloride channel proteins. The codon number used for this mutation was based on the available partial-length cDNA of CLCN1; when the full-length cDNA became known, the codon number was changed from 180 to 230 (<a href="#17" class="mim-tip-reference" title="George, A. L., Jr. <strong>Personal Communication.</strong> Nashville, Tenn. 4/14/1997."None>George, 1997</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7981750" 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 functional expression studies, <a href="#15" class="mim-tip-reference" title="Fahlke, C., Beck, C. L., George, A. L., Jr. <strong>A mutation in autosomal dominant myotonia congenita affects pore properties of the muscle chloride channel.</strong> Proc. Nat. Acad. Sci. 94: 2729-2734, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9122265/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9122265</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9122265[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.94.6.2729" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9122265">Fahlke et al. (1997)</a> found that the G230E mutation caused substantial changes in anion and cation selectivity, as well as a fundamental change in rectification of the current-voltage relationship. Whereas wildtype channels were characterized by pronounced inward rectification and a characteristic pattern of selectivity, G230E exhibited outward rectification at positive potentials and a different pattern of selectivity. Furthermore, the cation-to-anion permeability ratio of the mutant was much greater than that of the wildtype channel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9122265" 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">rs1563078827 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1563078827;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1563078827" 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=rs1563078827" 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=RCV000019086" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019086" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019086</a>
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<p>In affected members of a German family with recessive myotonia (<a href="/entry/255700">255700</a>), <a href="#25" class="mim-tip-reference" title="Lorenz, C., Meyer-Kleine, C., Steinmeyer, K., Koch, M. C., Jentsch, T. J. <strong>Genomic organization of the human muscle chloride channel CLC-1 and analysis of novel mutations leading to Becker-type myotonia.</strong> Hum. Molec. Genet. 3: 941-946, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951242/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951242</a>] [<a href="https://doi.org/10.1093/hmg/3.6.941" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7951242">Lorenz et al. (1994)</a> identified compound heterozygosity for 2 mutations in the CLCN1 gene: a 979G-A transition in a splice consensus site at the end of exon 8, and a 1488G-T transversion in exon 14, resulting in an arg496-to-ser (R496S; <a href="#0004">118425.0004</a>). Functional expression of R496S cRNA in Xenopus oocytes yielded no detectable currents. Furthermore, it did not suppress wildtype currents in coexpression assay, confirming it as a recessive mutation. The G-to-A transition in exon 8 was stated to affect the last nucleotide of the exon. If this interfered with mRNA splicing at that exon/intron boundary, the translation product would be terminated by a stop codon after 51 additional amino acids or other splice sites in the intron might be used. Alternatively, if splicing were normal, this mutation would lead to a substitution of isoleucine for valine at position 327 (V327I). Since this residue is not conserved among the members of this gene family and most members have negatively charged glutamate residues at this position, it is unlikely that such a substitution would have a dramatic effect on channel function. This would argue for an aberrant splicing as the effect of the G979A mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951242" 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 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121912801 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912801;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/rs121912801?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=rs121912801" 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=rs121912801" 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=RCV000019087 OR RCV000692794 OR RCV001781281 OR RCV004532392" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019087, RCV000692794, RCV001781281, RCV004532392" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019087...</a>
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<p>For discussion of the arg496-to-ser (R496S) mutation in the CLCN1 gene that was found in compound heterozygous state in affected members of a family with recessive myotonia (<a href="/entry/255700">255700</a>) by <a href="#25" class="mim-tip-reference" title="Lorenz, C., Meyer-Kleine, C., Steinmeyer, K., Koch, M. C., Jentsch, T. J. <strong>Genomic organization of the human muscle chloride channel CLC-1 and analysis of novel mutations leading to Becker-type myotonia.</strong> Hum. Molec. Genet. 3: 941-946, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951242/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951242</a>] [<a href="https://doi.org/10.1093/hmg/3.6.941" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7951242">Lorenz et al. (1994)</a>, see <a href="#0003">118425.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951242" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs746125212 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs746125212;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/rs746125212?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=rs746125212" 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=rs746125212" 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=RCV000019088 OR RCV000657922 OR RCV000810078 OR RCV003764473 OR RCV003989574" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019088, RCV000657922, RCV000810078, RCV003764473, RCV003989574" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019088...</a>
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<p>In affected members of a family with Becker myotonia congenita (<a href="/entry/255700">255700</a>), <a href="#18" class="mim-tip-reference" title="Koch, M. C., Meyer-Kleine, C., Otto, M., Ricker, K., Lorenz, C., Steinmeyer, K., Jentsch, T. J. <strong>Mutations in the CLCN1 gene leading to myotonia congenita Thomsen and generalized myotonia Becker. (Abstract)</strong> Am. J. Hum. Genet. 55 (suppl.): A226, 1994."None>Koch et al. (1994)</a> identified a mutation in the CLCN1 gene, resulting in a gly482-to-arg (G482R) substitution. Interestingly, this mutation producing a recessive phenotype is only 2 codons removed from a pro480-to-leu (P480L; <a href="#0006">118425.0006</a>) mutation which results in the dominant Thomsen type of myotonia congenita.</p>
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<strong>.0006 MYOTONIA CONGENITA, AUTOSOMAL DOMINANT</strong>
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CLCN1, PRO480LEU
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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> rs80356694 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356694;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/rs80356694?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=rs80356694" 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=rs80356694" 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=RCV000019089 OR RCV000020101 OR RCV001237767" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019089, RCV000020101, RCV001237767" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019089...</a>
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<p>In affected members of Thomsen's own family (<a href="#42" class="mim-tip-reference" title="Thomsen, J. <strong>Tonische Kraempfe in willkuerlich beweglichen Muskeln in Folge von ererbter psychischer Disposition: Ataxia muscularis?</strong> Arch. Psychiat. Nervenkr. 6: 702-718, 1876."None>Thomsen, 1876</a>; <a href="#41" class="mim-tip-reference" title="Thomasen, E. <strong>Myotonia, Thomsen's disease. Paramyotonia, and dystrophia myotonica.</strong> Op. Ex Domo Biol. Hered. Hum. U. Hafniensis 17: 11-251, 1948."None>Thomasen, 1948</a>) with autosomal dominant myotonia congenita (<a href="/entry/160800">160800</a>), <a href="#38" class="mim-tip-reference" title="Steinmeyer, K., Lorenz, C., Pusch, M., Koch, M. C., Jentsch, T. J. <strong>Multimeric structure of ClC-1 chloride channel revealed by mutations in dominant myotonia congenita (Thomsen).</strong> EMBO J. 13: 737-743, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8112288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8112288</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1994.tb06315.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8112288">Steinmeyer et al. (1994)</a> identified a heterozygous mutation in the CLCN1 gene, resulting in a pro480-to-leu (P480L) substitution. Functional expression studies showed that the P480L mutation dramatically inhibited normal CLCN1 channel function via a dominant-negative effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8112288" 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="#18" class="mim-tip-reference" title="Koch, M. C., Meyer-Kleine, C., Otto, M., Ricker, K., Lorenz, C., Steinmeyer, K., Jentsch, T. J. <strong>Mutations in the CLCN1 gene leading to myotonia congenita Thomsen and generalized myotonia Becker. (Abstract)</strong> Am. J. Hum. Genet. 55 (suppl.): A226, 1994."None>Koch et al. (1994)</a> also reported the P480L mutation as causative of Thomsen disease.</p><p><a href="#32" class="mim-tip-reference" title="Pusch, M., Steinmeyer, K., Koch, M. C., Jentsch, T. J. <strong>Mutations in dominant human myotonia congenita drastically alter the voltage dependence of the CIC-1 chloride channel.</strong> Neuron 15: 1455-1463, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845168/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845168</a>] [<a href="https://doi.org/10.1016/0896-6273(95)90023-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845168">Pusch et al. (1995)</a> transfected cDNA bearing the P480L mutation into Xenopus oocytes, demonstrating a large 90-mV shift of the gating toward positive voltages. In further structure studies, they replaced isoleucine 290 by 18 different amino acids. Substitution with valine shifted the gating by -17 millivolts. In all other replacements, the gating was either shifted to more positive voltages or resulted in no current above background. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8845168" 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="Colding-Jorgensen, E., Duno, M., Schwartz, M., Vissing, J. <strong>Decrement of compound muscle action potential is related to mutation type in myotonia congenita.</strong> Muscle Nerve 27: 449-455, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12661046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12661046</a>] [<a href="https://doi.org/10.1002/mus.10347" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12661046">Colding-Jorgensen et al. (2003)</a> found that all 6 patients with the dominant P480L mutation had CMAP decrements above 30%, which the authors suggested was correlated with the large voltage shift conferred by the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12661046" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 MYOTONIA LEVIOR</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> rs80356696 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356696;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/rs80356696?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=rs80356696" 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=rs80356696" 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=RCV000019090 OR RCV000020103 OR RCV000498537 OR RCV000685420 OR RCV001253100" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019090, RCV000020103, RCV000498537, RCV000685420, RCV001253100" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019090...</a>
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<p>In 2 brothers with a mild form of dominant myotonia, referred to as myotonia levior (see <a href="/entry/160800">160800</a>), <a href="#23" class="mim-tip-reference" title="Lehmann-Horn, F., Mailander, V., Heine, R., George, A. L. <strong>Myotonia levior is a chloride channel disorder.</strong> Hum. Molec. Genet. 4: 1397-1402, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581380</a>] [<a href="https://doi.org/10.1093/hmg/4.8.1397" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7581380">Lehmann-Horn et al. (1995)</a> identified a 1655A-G transition in exon 15 of the CLCN1 gene, resulting in a gln552-to-arg (Q552R) substitution. Their affected mother also had the mutation. The findings indicated that myotonia levior is a variant or allelic form of Thomsen disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7581380" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By functional expression studies, <a href="#36" class="mim-tip-reference" title="Ryan, A., Rudel, R., Kuchenbecker, M., Fahlke, C. <strong>A novel alteration of muscle chloride channel gating in myotonia levior.</strong> J. Physiol. 545: 345-354, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12456816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12456816</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12456816[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/10.1113/jphysiol.2002.027037" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12456816">Ryan et al. (2002)</a> demonstrated that CLCN1 channels with the Q552R mutation were formed normally, but had altered gating properties. Voltage dependence of the mutant channels was shifted by more than +90 mV compared to wildtype channels, resulting in a reduction in the open probability of the channel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12456816" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 MYOTONIA CONGENITA, AUTOSOMAL DOMINANT</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs80356690 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356690;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/rs80356690?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=rs80356690" 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=rs80356690" 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=RCV000019091 OR RCV000020117 OR RCV000626584 OR RCV000690053 OR RCV000711241 OR RCV001196224 OR RCV004528125" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019091, RCV000020117, RCV000626584, RCV000690053, RCV000711241, RCV001196224, RCV004528125" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019091...</a>
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<p>In affected members of a family with Thomsen myotonia (<a href="/entry/160800">160800</a>), <a href="#23" class="mim-tip-reference" title="Lehmann-Horn, F., Mailander, V., Heine, R., George, A. L. <strong>Myotonia levior is a chloride channel disorder.</strong> Hum. Molec. Genet. 4: 1397-1402, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581380</a>] [<a href="https://doi.org/10.1093/hmg/4.8.1397" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7581380">Lehmann-Horn et al. (1995)</a> identified an 870C-G transversion in the CLCN1 gene, resulting in an ile290-to-met (I290M) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7581380" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs768119034 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs768119034;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/rs768119034?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=rs768119034" 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=rs768119034" 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=RCV000395981 OR RCV000552780 OR RCV000664241 OR RCV000778142 OR RCV001262336 OR RCV001753742 OR RCV002259330 OR RCV003319191" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000395981, RCV000552780, RCV000664241, RCV000778142, RCV001262336, RCV001753742, RCV002259330, RCV003319191" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000395981...</a>
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<p>In patients with Becker myotonia (<a href="/entry/255700">255700</a>), <a href="#28" class="mim-tip-reference" title="Meyer-Kleine, C., Ricker, K., Otto, M., Koch, M. C. <strong>A recurrent 14 bp deletion in the CLCN1 gene associated with generalized myotonia (Becker).</strong> Hum. Molec. Genet. 3: 1015-1016, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951215</a>] [<a href="https://doi.org/10.1093/hmg/3.6.1015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7951215">Meyer-Kleine et al. (1994)</a> identified a 14-bp deletion in exon 13 of the CLCN1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951215" 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 family in which the index patient and his mother had been examined by <a href="#5" class="mim-tip-reference" title="Becker, P. E. <strong>Myotonia Congenita and Syndromes associated with Myotonia: Clinical-Genetic Studies of the Nondystrophic Myotonias.</strong> Stuttgart: Georg Thieme (pub.) 1977."None>Becker (1977)</a>, who classified their disorder as dominant myotonia congenita, <a href="#23" class="mim-tip-reference" title="Lehmann-Horn, F., Mailander, V., Heine, R., George, A. L. <strong>Myotonia levior is a chloride channel disorder.</strong> Hum. Molec. Genet. 4: 1397-1402, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581380</a>] [<a href="https://doi.org/10.1093/hmg/4.8.1397" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7581380">Lehmann-Horn et al. (1995)</a> found that the proband was homozygous for a 14-bp deletion (involving nucleotides 1437-1450) in exon 13 of the CLCN1 gene. Both nonmyotonic sons of the index patient were heterozygous for the deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7581380" 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 French Canadian patients with recessive myotonia, <a href="#11" class="mim-tip-reference" title="Dupre, N., Chrestian, N., Bouchard, J.-P., Rossignol, E., Brunet, D., Sternberg, D., Brias, B., Mathieu, J., Puymirat, J. <strong>Clinical, electrophysiologic, and genetic study of non-dystrophic myotonia in French-Canadians.</strong> Neuromusc. Disord. 19: 330-334, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18337100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18337100</a>] [<a href="https://doi.org/10.1016/j.nmd.2008.01.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18337100">Dupre et al. (2009)</a> found that homozygosity for the 14-bp deletion resulted in a severe phenotype with generalized hypertrophy, moderate myotonia, and transient weakness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18337100" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0010 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121912805 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912805;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/rs121912805?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=rs121912805" 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=rs121912805" 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=RCV000019093 OR RCV001041229 OR RCV001781282 OR RCV002468557" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019093, RCV001041229, RCV001781282, RCV002468557" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019093...</a>
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<p>In 2 sibs with autosomal recessive myotonia congenita (<a href="/entry/255700">255700</a>), <a href="#32" class="mim-tip-reference" title="Pusch, M., Steinmeyer, K., Koch, M. C., Jentsch, T. J. <strong>Mutations in dominant human myotonia congenita drastically alter the voltage dependence of the CIC-1 chloride channel.</strong> Neuron 15: 1455-1463, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845168/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845168</a>] [<a href="https://doi.org/10.1016/0896-6273(95)90023-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845168">Pusch et al. (1995)</a> identified compound heterozygosity for 2 mutations in the CLCN1 gene: glu291-to-lys (E291K) and arg894-to-ter (R894X; <a href="#0015">118425.0015</a>). Functional expression studies showed that the E291K channels did not yield currents between -140 and 100 millivolts, indicating that this mutation totally abolished channel activity. In contrast to the mutation in the neighboring amino acid (I290M; <a href="#0008">118425.0008</a>), which acts as a dominant as a result of interactions with wildtype monomers, the E291K mutation is recessive. Whereas the I290M mutant shifts the voltage dependence of chloride channels positive (via homomers or heteromers with wildtype subunits), the E291K mutation shows no evidence of interaction and does not shift the voltage dependence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8845168" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0011 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs80356702 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356702;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/rs80356702?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=rs80356702" 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=rs80356702" 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=RCV000019094 OR RCV000019095 OR RCV000020121 OR RCV000516960 OR RCV000626585 OR RCV000763169" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019094, RCV000019095, RCV000020121, RCV000516960, RCV000626585, RCV000763169" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019094...</a>
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<p>The arg317-to-gln (R317Q) mutation illustrates the resultant occurrence of either autosomal dominant myotonia congenita (<a href="/entry/160800">160800</a>) or autosomal recessive myotonia congenita (<a href="/entry/255700">255700</a>), depending on the family background. <a href="#29" class="mim-tip-reference" title="Meyer-Kleine, C., Steinmeyer, K., Ricker, K., Jentsch, T. J., Koch, M. C. <strong>Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCN1) leading to myotonia.</strong> Am. J. Hum. Genet. 57: 1325-1334, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8533761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8533761</a>]" pmid="8533761">Meyer-Kleine et al. (1995)</a> observed the R317Q mutation in dominant Thomsen myotonia congenita; <a href="#13" class="mim-tip-reference" title="Esteban, J., Neumeyer, A. M., McKenna-Yasek, D., Brown, R. H. <strong>Identification of two mutations and a polymorphism in the chloride channel CLCN-1 in patients with Becker's generalized myotonia.</strong> Neurogenetics 1: 185-188, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10737121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10737121</a>] [<a href="https://doi.org/10.1007/s100480050027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10737121">Esteban et al. (1998)</a> observed it in Becker myotonia congenita and pointed to other mutations that had been observed as a recessive or a dominant, depending on the particular family. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8533761+10737121" 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> rs121912807 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912807;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/rs121912807?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=rs121912807" 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=rs121912807" 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=RCV000019096 OR RCV001382414" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019096, RCV001382414" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019096...</a>
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<p>In a boy with Becker myotonia congenita (<a href="/entry/255700">255700</a>), <a href="#46" class="mim-tip-reference" title="Zhang, J., Sanguinetti, M. C., Kwiecinski, H., Ptacek, L. J. <strong>Mechanism of inverted activation of ClC-1 channels caused by a novel myotonia congenita mutation.</strong> J. Biol. Chem. 275: 2999-3005, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10644771/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10644771</a>] [<a href="https://doi.org/10.1074/jbc.275.4.2999" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10644771">Zhang et al. (2000)</a> identified a C-to-T transition at codon 1495 in exon 14 of the CLCN1 gene, resulting in a gly499-to-arg (G499R) substitution in the putative transmembrane domain 10 of the CLCN1 protein. In contrast to normal CLCN1 channels that deactivate upon hyperpolarization, functional expression of G499R CLCN1 yielded a hyperpolarization-activated chloride current when measured in the presence of a high intracellular chloride concentration. Current was abolished when measured with a physiologic chloride transmembrane gradient. Electrophysiologic analysis of other gly449 mutants suggested that the positive charge introduced by the G499R mutation may be responsible for this unique gating behavior. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10644771" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0013 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs140026363 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs140026363;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/rs140026363?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=rs140026363" 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=rs140026363" 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=RCV000019097 OR RCV001382411" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019097, RCV001382411" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019097...</a>
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<p>In 2 African American sibs with autosomal recessive myotonia congenita (<a href="/entry/255700">255700</a>), <a href="#31" class="mim-tip-reference" title="Nagamitsu, S., Matsuura, T., Khajavi, M., Armstrong, R., Gooch, C., Harati, Y., Ashizawa, T. <strong>A 'dystrophic' variant of autosomal recessive myotonia congenita caused by novel mutations in the CLCN1 gene.</strong> Neurology 55: 1697-1703, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11113225/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11113225</a>] [<a href="https://doi.org/10.1212/wnl.55.11.1697" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11113225">Nagamitsu et al. (2000)</a> identified compound heterozygosity for 2 mutations in the CLCN1 gene: a 1-bp insertion (831insG) in exon 7, resulting in a premature termination codon at codon 289, and a C-to-T transition in exon 23, resulting in a pro932-to-leu (P932L; <a href="#0014">118425.0014</a>) substitution. In addition to generalized myotonia and proximal muscle hypertrophy, the sibs also displayed progressive muscle weakness, joint contractures, and dystrophic muscle pathology. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11113225" 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> rs80356706 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356706;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/rs80356706?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=rs80356706" 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=rs80356706" 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=RCV000019085 OR RCV000020108 OR RCV000478940 OR RCV000638250" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019085, RCV000020108, RCV000478940, RCV000638250" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019085...</a>
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<p>For discussion of the pro932-to-leu (P932L) mutation in the CLCN1 gene that was found in compound heterozygous state in sibs with autosomal recessive myotonia congenita (<a href="/entry/255700">255700</a>) by <a href="#31" class="mim-tip-reference" title="Nagamitsu, S., Matsuura, T., Khajavi, M., Armstrong, R., Gooch, C., Harati, Y., Ashizawa, T. <strong>A 'dystrophic' variant of autosomal recessive myotonia congenita caused by novel mutations in the CLCN1 gene.</strong> Neurology 55: 1697-1703, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11113225/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11113225</a>] [<a href="https://doi.org/10.1212/wnl.55.11.1697" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11113225">Nagamitsu et al. (2000)</a>, see <a href="#0013">118425.0013</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11113225" 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>.0015 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs55960271 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs55960271;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/rs55960271?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=rs55960271" 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=rs55960271" 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=RCV000019098 OR RCV000019099 OR RCV000020107 OR RCV000292791 OR RCV000626582 OR RCV000627759 OR RCV001564017 OR RCV001794458 OR RCV001813999 OR RCV004515784 OR RCV004737160" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019098, RCV000019099, RCV000020107, RCV000292791, RCV000626582, RCV000627759, RCV001564017, RCV001794458, RCV001813999, RCV004515784, RCV004737160" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019098...</a>
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<p>For discussion of the arg894-to-ter (R894X) mutation in the CLCN1 gene that was found in compound heterozygous state in sibs with autosomal recessive myotonia congenita (<a href="/entry/255700">255700</a>) by <a href="#32" class="mim-tip-reference" title="Pusch, M., Steinmeyer, K., Koch, M. C., Jentsch, T. J. <strong>Mutations in dominant human myotonia congenita drastically alter the voltage dependence of the CIC-1 chloride channel.</strong> Neuron 15: 1455-1463, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845168/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845168</a>] [<a href="https://doi.org/10.1016/0896-6273(95)90023-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845168">Pusch et al. (1995)</a>, see <a href="#0010">118425.0010</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8845168" 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 patients with both autosomal recessive and autosomal dominant (<a href="/entry/160800">160800</a>) myotonia congenita, <a href="#29" class="mim-tip-reference" title="Meyer-Kleine, C., Steinmeyer, K., Ricker, K., Jentsch, T. J., Koch, M. C. <strong>Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCN1) leading to myotonia.</strong> Am. J. Hum. Genet. 57: 1325-1334, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8533761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8533761</a>]" pmid="8533761">Meyer-Kleine et al. (1995)</a> identified a mutation in the CLCN1 gene, resulting in an R894X substitution. Functional expression of the R894X mutant in Xenopus oocytes revealed a large reduction, but not complete abolition, of chloride currents. Further, it had a weak dominant-negative effect on wildtype currents in coexpression studies. Reduction of currents predicted for heterozygous carriers were close to the borderline value, sufficient to elicit myotonia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8533761" 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="#40" class="mim-tip-reference" title="Sun, C., Tranebjaerg, L., Torbergsen, T., Holmgren, G., Van Ghelue, M. <strong>Spectrum of CLCN1 mutations in patients with myotonia congenita in northern Scandinavia.</strong> Europ. J. Hum. Genet. 9: 903-909, 2001. Note: Erratum: Europ. J. Hum. Genet. 18: 264 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11840191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11840191</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200736" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11840191">Sun et al. (2001)</a> found a carrier frequency of 0.87% for the R894X mutation in the northern Scandinavian population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11840191" 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 French Canadian family with myotonia, <a href="#11" class="mim-tip-reference" title="Dupre, N., Chrestian, N., Bouchard, J.-P., Rossignol, E., Brunet, D., Sternberg, D., Brias, B., Mathieu, J., Puymirat, J. <strong>Clinical, electrophysiologic, and genetic study of non-dystrophic myotonia in French-Canadians.</strong> Neuromusc. Disord. 19: 330-334, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18337100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18337100</a>] [<a href="https://doi.org/10.1016/j.nmd.2008.01.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18337100">Dupre et al. (2009)</a> found that the R894X mutation could be expressed in a semidominant or recessive manner. The proband, who was heterozygous for the R894X mutation, had muscle stiffness and mild warm-up phenomenon, but no significant percussion myotonia and no myotonia on EMG. In contrast, her daughters, who were compound heterozygous for the R894X and R300X (<a href="#0017">118425.0017</a>) mutations, showed a moderately severe phenotype with generalized hypertrophy consistent with autosomal recessive Becker myotonia. This compound heterozygous genotype showed resistance to phenytoin, mexiletine, and quinine. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18337100" 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">rs80356699 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356699;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80356699" 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=rs80356699" 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=RCV000019100 OR RCV000020109 OR RCV001049292" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019100, RCV000020109, RCV001049292" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019100...</a>
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<p>In affected members of a family with autosomal dominant myotonia congenita (<a href="/entry/160800">160800</a>), <a href="#9" class="mim-tip-reference" title="Colding-Jorgensen, E., Duno, M., Schwartz, M., Vissing, J. <strong>Decrement of compound muscle action potential is related to mutation type in myotonia congenita.</strong> Muscle Nerve 27: 449-455, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12661046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12661046</a>] [<a href="https://doi.org/10.1002/mus.10347" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12661046">Colding-Jorgensen et al. (2003)</a> identified a heterozygous A-to-G transition in the CLCN1 gene, resulting in a met128-to-val (M128V) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12661046" 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>.0017 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1586496726 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1586496726;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1586496726" 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=rs1586496726" 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=RCV000019101" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019101" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019101</a>
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<p>For discussion of the arg300-to-ter (R300X) mutation in the CLCN1 gene that was found in compound heterozygous state in patients with autosomal recessive myotonia congenita (<a href="/entry/255700">255700</a>) by <a href="#11" class="mim-tip-reference" title="Dupre, N., Chrestian, N., Bouchard, J.-P., Rossignol, E., Brunet, D., Sternberg, D., Brias, B., Mathieu, J., Puymirat, J. <strong>Clinical, electrophysiologic, and genetic study of non-dystrophic myotonia in French-Canadians.</strong> Neuromusc. Disord. 19: 330-334, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18337100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18337100</a>] [<a href="https://doi.org/10.1016/j.nmd.2008.01.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18337100">Dupre et al. (2009)</a>, see <a href="#0015">118425.0015</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18337100" 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>.0018 MYOTONIA CONGENITA, AUTOSOMAL DOMINANT</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121912810 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912810;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121912810" 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=rs121912810" 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=RCV000019102 OR RCV003387727" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019102, RCV003387727" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019102...</a>
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<p>In 2 French Canadian women with autosomal dominant myotonia congenita (<a href="/entry/160800">160800</a>), <a href="#11" class="mim-tip-reference" title="Dupre, N., Chrestian, N., Bouchard, J.-P., Rossignol, E., Brunet, D., Sternberg, D., Brias, B., Mathieu, J., Puymirat, J. <strong>Clinical, electrophysiologic, and genetic study of non-dystrophic myotonia in French-Canadians.</strong> Neuromusc. Disord. 19: 330-334, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18337100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18337100</a>] [<a href="https://doi.org/10.1016/j.nmd.2008.01.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18337100">Dupre et al. (2009)</a> identified a heterozygous ser189-to-phe (S189F) substitution in the CLCN1 gene. Both women had mild fluctuating myotonia and mild muscle hypertrophy and reported aggravation of symptoms with menstrual periods and pregnancy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18337100" 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>.0019 MYOTONIA CONGENITA, AUTOSOMAL DOMINANT</strong>
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MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE, INCLUDED
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019103 OR RCV000019104" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019103, RCV000019104" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019103...</a>
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<p><a href="#11" class="mim-tip-reference" title="Dupre, N., Chrestian, N., Bouchard, J.-P., Rossignol, E., Brunet, D., Sternberg, D., Brias, B., Mathieu, J., Puymirat, J. <strong>Clinical, electrophysiologic, and genetic study of non-dystrophic myotonia in French-Canadians.</strong> Neuromusc. Disord. 19: 330-334, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18337100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18337100</a>] [<a href="https://doi.org/10.1016/j.nmd.2008.01.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18337100">Dupre et al. (2009)</a> identified a heterozygous or homozygous trp433-to-arg (W433R) substitution in the CLCN1 gene in French Canadian patients with autosomal dominant (<a href="/entry/160800">160800</a>) and recessive (<a href="/entry/255700">255700</a>) myotonia, respectively. The recessive phenotype was characterized by severe myotonia, dysphagia, generalized hypertrophy predominant in lower limb muscles, and the warm-up phenomenon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18337100" 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>.0020 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
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CLCN1, DUP, EX8-14
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000033240" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000033240" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000033240</a>
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<p>In 2 unrelated Iraqi women with severe infantile-onset myotonia congenita (<a href="/entry/255700">255700</a>), <a href="#34" class="mim-tip-reference" title="Raja Rayan, D. L., Haworth, A., Sud, R., Matthews, E., Fialho, D., Burge, J., Portaro, S., Schorge, S., Tuin, K., Lunt, P., McEntagart, M., Toscano, A., Davis, M. B., Hanna, M. G. <strong>A new explanation for recessive myotonia congenita: exon deletions and duplications in CLCN1.</strong> Neurology 78: 1953-1958, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22649220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22649220</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22649220[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/10.1212/WNL.0b013e318259e19c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22649220">Raja Rayan et al. (2012)</a> identified a homozygous duplication of exons 8 through 14 of the CLCN1 gene, predicted to result in a frameshift. Both patients came from consanguineous families and had multiple affected family members. The duplication was identified by multiplex ligation-dependent probe amplification (MLPA) specific to the CLCN1 gene, and was not found in 124 control chromosomes or in a variant database. Haplotype analysis suggested a founder effect for this duplication mutation. <a href="#34" class="mim-tip-reference" title="Raja Rayan, D. L., Haworth, A., Sud, R., Matthews, E., Fialho, D., Burge, J., Portaro, S., Schorge, S., Tuin, K., Lunt, P., McEntagart, M., Toscano, A., Davis, M. B., Hanna, M. G. <strong>A new explanation for recessive myotonia congenita: exon deletions and duplications in CLCN1.</strong> Neurology 78: 1953-1958, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22649220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22649220</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22649220[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/10.1212/WNL.0b013e318259e19c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22649220">Raja Rayan et al. (2012)</a> concluded that copy number variation involving the CLCN1 gene is an important genetic mechanism in patients with recessive myotonia congenita, and that MLPA analysis may aid in genetic counseling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22649220" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0021" class="mim-anchor"></a>
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<strong>.0021 VARIANT OF UNKNOWN SIGNIFICANCE</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> rs142539932 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs142539932;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/rs142539932?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=rs142539932" 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=rs142539932" 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=RCV000180791 OR RCV000195160 OR RCV000535831 OR RCV003488433" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000180791, RCV000195160, RCV000535831, RCV003488433" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000180791...</a>
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<p>This variant is classified as a variant of unknown significance because its contribution to idiopathic generalized epilepsy (EIG; see <a href="/entry/600669">600669</a>) has not been confirmed.</p><p>In a 26-year-old Italian woman with EIG, <a href="#8" class="mim-tip-reference" title="Chen, T. T., Klassen, T. L., Goldman, A. M., Marini, C., Guerrini, R., Noebels, J. L. <strong>Novel brain expression of ClC-1 chloride channels and enrichment of CLCN1 variants in epilepsy.</strong> Neurology 80: 1078-1085, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23408874/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23408874</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23408874[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/10.1212/WNL.0b013e31828868e7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23408874">Chen et al. (2013)</a> identified a de novo heterozygous c.2926C-T transition (c.2926C-T, NM_000083) in exon 23 of the CLCN1 gene, resulting in an arg976-to-ter (R976X) substitution and truncation of the distal C terminus by 12 residues. The mutation, which was found by exome sequencing of 291 patients with epilepsy, was not found in the dbSNP or 1000 Genomes Project databases. The patient had generalized pharmacoresistant epilepsy with mixed seizure types, including generalized tonic-clonic and absence seizures. Her first seizure occurred during a febrile illness at age 11 months. EEG repeatedly showed generalized spike-wave discharges. In addition, she presented with myotonic writer's cramp at age 9 years, which subsequently resolved. EMG as an adult showed no evidence of myotonic discharges. Brain MRI and cognitive function were normal. Functional studies of the variant were not performed, but <a href="#8" class="mim-tip-reference" title="Chen, T. T., Klassen, T. L., Goldman, A. M., Marini, C., Guerrini, R., Noebels, J. L. <strong>Novel brain expression of ClC-1 chloride channels and enrichment of CLCN1 variants in epilepsy.</strong> Neurology 80: 1078-1085, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23408874/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23408874</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23408874[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/10.1212/WNL.0b013e31828868e7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23408874">Chen et al. (2013)</a> found expression of the CLCN1 gene in multiple human brain regions, and suggested that the mutation identified in this patient could result in neuronal hyperexcitability, thus contributing to the seizure phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23408874" 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>.0022 MYOTONIA CONGENITA, AUTOSOMAL DOMINANT</strong>
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CLCN1, GLN412PRO
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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> rs1279658001 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1279658001;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/rs1279658001?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=rs1279658001" 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=rs1279658001" 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=RCV001382412 OR RCV002251767" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001382412, RCV002251767" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001382412...</a>
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<p>In a Costa Rican patient (family 4-CR14) with autosomal dominant myotonia congenita (<a href="/entry/160800">160800</a>), <a href="#43" class="mim-tip-reference" title="Vindas-Smith, R., Fiore, M., Vasquez, M., Cuenca, P., del Valle, G., Lagostena, L., Gaitan-Penas, H., Estevez, R., Pusch, M., Morales, F. <strong>Identification and functional characterization of CLCN1 mutations found in nondystrophic myotonia patients.</strong> Hum. Mutat. 37: 74-83, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26510092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26510092</a>] [<a href="https://doi.org/10.1002/humu.22916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26510092">Vindas-Smith et al. (2016)</a> identified a heterozygous c.1235A-C transversion in exon 11 of the CLCN1 gene, resulting in a gln412-to-pro (Q412P) substitution. The mutation, which was identified by bidirectional sequencing of the CLCN1 gene and confirmed by RFLP-PCR, was also found in the patient's asymptomatic (self-reported) mother and 2 sibs. Functional studies of CLCN1 with the Q412P mutation expressed in Xenopus oocytes showed reduced surface expression and reduced current density but did not display a dominant-negative effect when coexpressed with wildtype CLCN1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26510092" 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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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>REFERENCES</strong>
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<a id="Adrian1974" class="mim-anchor"></a>
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Adrian, R. H., Bryant, S. H.
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<strong>On the repetitive discharge in myotonic muscle fibres.</strong>
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J. Physiol. 240: 505-515, 1974.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4420758/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4420758</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4420758" 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/10.1113/jphysiol.1974.sp010620" target="_blank">Full Text</a>]
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Altamura, C., Lucchiari, S., Sahbani, D., Ulzi, G., Comi, G. P., D'Ambrosio, P., Petillo, R., Politano, L., Vercelli, L., Mongini, T., Dotti, M. T., Cardani, R., Meola, G., Lo Monaco, M., Matthews, E., Hanna, M. G., Carratu, M. R., Conte, D., Imbrici, P., Desaphy, J.-F.
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<strong>The analysis of myotonia congenita mutations discloses functional clusters of amino acids within the CBS2 domain and the C-terminal peptide of the CLC-1 channel.</strong>
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Hum. Mutat. 39: 1273-1283, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29935101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29935101</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29935101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.23581" target="_blank">Full Text</a>]
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Aminoff, M. J., Layzer, R. B., Satya-Murti, S., Faden, A. I.
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<strong>The declining electrical response of muscle to repetitive nerve stimulation in myotonia.</strong>
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Neurology 27: 812-816, 1977.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/561337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">561337</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=561337" 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/10.1212/wnl.27.9.812" target="_blank">Full Text</a>]
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Beck, C. L., Fahlke, C., George, A. L., Jr.
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<strong>Molecular basis for decreased muscle chloride conductance in the myotonic goat.</strong>
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Proc. Nat. Acad. Sci. 93: 11248-11252, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8855341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8855341</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8855341" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.93.20.11248" target="_blank">Full Text</a>]
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Becker, P. E.
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<strong>Myotonia Congenita and Syndromes associated with Myotonia: Clinical-Genetic Studies of the Nondystrophic Myotonias.</strong>
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Stuttgart: Georg Thieme (pub.) 1977.
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Bryant, S. H.
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<strong>Muscle membrane of normal and myotonic goats in normal and low external chloride. (Abstract)</strong>
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Fed. Proc. 21: 312 only, 1962.
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Charlet-B, N., Savkur, R. S., Singh, G., Philips, A. V., Grice, E. A., Cooper, T. A.
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<strong>Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing.</strong>
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Molec. Cell 10: 45-53, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12150906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12150906</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12150906" 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/s1097-2765(02)00572-5" target="_blank">Full Text</a>]
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Chen, T. T., Klassen, T. L., Goldman, A. M., Marini, C., Guerrini, R., Noebels, J. L.
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<strong>Novel brain expression of ClC-1 chloride channels and enrichment of CLCN1 variants in epilepsy.</strong>
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Neurology 80: 1078-1085, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23408874/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23408874</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23408874[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23408874" 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/10.1212/WNL.0b013e31828868e7" target="_blank">Full Text</a>]
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Colding-Jorgensen, E., Duno, M., Schwartz, M., Vissing, J.
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<strong>Decrement of compound muscle action potential is related to mutation type in myotonia congenita.</strong>
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Muscle Nerve 27: 449-455, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12661046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12661046</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12661046" 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/mus.10347" target="_blank">Full Text</a>]
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Duno, M., Colding-Jorgensen, E., Grunnet, M., Jespersen, T., Vissing, J., Schwartz, M.
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<strong>Difference in allelic expression of the CLCN1 gene and the possible influence on the myotonia congenita phenotype.</strong>
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Europ. J. Hum. Genet. 12: 738-743, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15162127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15162127</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15162127" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.ejhg.5201218" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Dupre2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dupre, N., Chrestian, N., Bouchard, J.-P., Rossignol, E., Brunet, D., Sternberg, D., Brias, B., Mathieu, J., Puymirat, J.
|
|
<strong>Clinical, electrophysiologic, and genetic study of non-dystrophic myotonia in French-Canadians.</strong>
|
|
Neuromusc. Disord. 19: 330-334, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18337100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18337100</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18337100" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.nmd.2008.01.007" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Dutzler2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dutzler, R., Campbell, E. B., Cadene, M., Chait, B. T., MacKinnon, R.
|
|
<strong>X-ray structure of a CIC chloride channel at 3.0 angstrom reveals the molecular basis of anion selectivity.</strong>
|
|
Nature 415: 287-294, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11796999/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11796999</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11796999" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/415287a" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Esteban1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Esteban, J., Neumeyer, A. M., McKenna-Yasek, D., Brown, R. H.
|
|
<strong>Identification of two mutations and a polymorphism in the chloride channel CLCN-1 in patients with Becker's generalized myotonia.</strong>
|
|
Neurogenetics 1: 185-188, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10737121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10737121</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10737121" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s100480050027" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Estevez2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Estevez, R., Schroeder, B. C., Accardi, A., Jentsch, T. J., Pusch, M.
|
|
<strong>Conservation of chloride channel structure revealed by an inhibitor binding site in CIC-1.</strong>
|
|
Neuron 38: 47-59, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12691663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12691663</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12691663" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0896-6273(03)00168-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Fahlke1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fahlke, C., Beck, C. L., George, A. L., Jr.
|
|
<strong>A mutation in autosomal dominant myotonia congenita affects pore properties of the muscle chloride channel.</strong>
|
|
Proc. Nat. Acad. Sci. 94: 2729-2734, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9122265/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9122265</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9122265[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9122265" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.94.6.2729" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="George1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
George, A. L., Jr., Crackower, M. A., Abdalla, J. A., Hudson, A. J., Ebers, G. C.
|
|
<strong>Molecular basis of Thomsen's disease (autosomal dominant myotonia congenita).</strong>
|
|
Nature Genet. 3: 305-310, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7981750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7981750</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7981750" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0493-305" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="George1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
George, A. L., Jr.
|
|
<strong>Personal Communication.</strong>
|
|
Nashville, Tenn. 4/14/1997.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Koch1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Koch, M. C., Meyer-Kleine, C., Otto, M., Ricker, K., Lorenz, C., Steinmeyer, K., Jentsch, T. J.
|
|
<strong>Mutations in the CLCN1 gene leading to myotonia congenita Thomsen and generalized myotonia Becker. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 55 (suppl.): A226, 1994.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Koch1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Koch, M. C., Ricker, K., Otto, M., Wolf, F., Zoll, B., Lorenz, C., Steinmeyer, K., Jentsch, T. J.
|
|
<strong>Evidence for genetic homogeneity in autosomal recessive generalised myotonia (Becker).</strong>
|
|
J. Med. Genet. 30: 914-917, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8301644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8301644</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8301644" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.30.11.914" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Koch1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Koch, M. C., Steinmeyer, K., Lorenz, C., Ricker, K., Wolf, F., Otto, M., Zoll, B., Lehmann-Horn, F., Grzeschik, K.-H., Jentsch, T. J.
|
|
<strong>The skeletal muscle chloride channel in dominant and recessive human myotonia.</strong>
|
|
Science 257: 797-800, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1379744/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1379744</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1379744" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1379744" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Koty1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Koty, P. P., Marks, H. G., Turel, A., Flagler, D., Angelini, C., Pegoraro, E., Vancott, A. C., Manchester, D., Zonana, J., Bird, T. D., Hoffman, E. P.
|
|
<strong>Linkage analysis of Thomsen and Becker myotonia families. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 55 (suppl.): A227, 1994.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Kubisch1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kubisch, C., Schmidt-Rose, T., Fontaine, B., Bretag, A. H., Jentsch, T. J.
|
|
<strong>ClC-1 chloride channel mutations in myotonia congenita: variable penetrance of mutations shifting the voltage dependence.</strong>
|
|
Hum. Molec. Genet. 7: 1753-1760, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9736777/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9736777</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9736777" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/7.11.1753" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Lehmann-Horn1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lehmann-Horn, F., Mailander, V., Heine, R., George, A. L.
|
|
<strong>Myotonia levior is a chloride channel disorder.</strong>
|
|
Hum. Molec. Genet. 4: 1397-1402, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581380</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7581380" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/4.8.1397" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Lipicky1966" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lipicky, R. J., Bryant, S. H.
|
|
<strong>Sodium, potassium, and chloride fluxes in intercostal muscle from normal goats and goats with hereditary myotonia.</strong>
|
|
J. Gen. Physiol. 50: 89-111, 1966.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5971035/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5971035</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5971035" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1085/jgp.50.1.89" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Lorenz1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lorenz, C., Meyer-Kleine, C., Steinmeyer, K., Koch, M. C., Jentsch, T. J.
|
|
<strong>Genomic organization of the human muscle chloride channel CLC-1 and analysis of novel mutations leading to Becker-type myotonia.</strong>
|
|
Hum. Molec. Genet. 3: 941-946, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951242/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951242</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951242" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/3.6.941" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Mailander1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mailander, V., Heine, R., Deymeer, F., Lehmann-Horn, F.
|
|
<strong>Novel muscle chloride channel mutations and their effects on heterozygous carriers.</strong>
|
|
Am. J. Hum. Genet. 58: 317-324, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8571958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8571958</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8571958" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Mankodi2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mankodi, A., Takahashi, M. P., Jiang, H., Beck, C. L., Bowers, W. J., Moxley, R. T., Cannon, S. C., Thornton, C. A.
|
|
<strong>Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy.</strong>
|
|
Molec. Cell 10: 35-44, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12150905/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12150905</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12150905" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s1097-2765(02)00563-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Meyer-Kleine1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meyer-Kleine, C., Ricker, K., Otto, M., Koch, M. C.
|
|
<strong>A recurrent 14 bp deletion in the CLCN1 gene associated with generalized myotonia (Becker).</strong>
|
|
Hum. Molec. Genet. 3: 1015-1016, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951215</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951215" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/3.6.1015" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Meyer-Kleine1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meyer-Kleine, C., Steinmeyer, K., Ricker, K., Jentsch, T. J., Koch, M. C.
|
|
<strong>Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCN1) leading to myotonia.</strong>
|
|
Am. J. Hum. Genet. 57: 1325-1334, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8533761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8533761</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8533761" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Mindell2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mindell, J. A., Maduke, M., Miller, C., Grigorieff, N.
|
|
<strong>Projection structure of a CIC-type chloride channel at 6.5-angstrom resolution.</strong>
|
|
Nature 409: 219-223, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11196649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11196649</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11196649" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/35051631" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Nagamitsu2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nagamitsu, S., Matsuura, T., Khajavi, M., Armstrong, R., Gooch, C., Harati, Y., Ashizawa, T.
|
|
<strong>A 'dystrophic' variant of autosomal recessive myotonia congenita caused by novel mutations in the CLCN1 gene.</strong>
|
|
Neurology 55: 1697-1703, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11113225/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11113225</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11113225" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/wnl.55.11.1697" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Pusch1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pusch, M., Steinmeyer, K., Koch, M. C., Jentsch, T. J.
|
|
<strong>Mutations in dominant human myotonia congenita drastically alter the voltage dependence of the CIC-1 chloride channel.</strong>
|
|
Neuron 15: 1455-1463, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845168/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845168</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8845168" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0896-6273(95)90023-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Pusch2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pusch, M.
|
|
<strong>Myotonia caused by mutations in the muscle chloride channel gene CLCN1.</strong>
|
|
Hum. Mutat. 19: 423-434, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11933197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11933197</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11933197" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.10063" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Raja Rayan2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Raja Rayan, D. L., Haworth, A., Sud, R., Matthews, E., Fialho, D., Burge, J., Portaro, S., Schorge, S., Tuin, K., Lunt, P., McEntagart, M., Toscano, A., Davis, M. B., Hanna, M. G.
|
|
<strong>A new explanation for recessive myotonia congenita: exon deletions and duplications in CLCN1.</strong>
|
|
Neurology 78: 1953-1958, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22649220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22649220</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22649220[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22649220" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/WNL.0b013e318259e19c" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Rudel1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rudel, R.
|
|
<strong>The myotonic mouse--a realistic model for the study of human recessive generalized myotonia.</strong>
|
|
Trends Neurosci. 13: 1-3, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1688667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1688667</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1688667" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0166-2236(90)90049-g" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Ryan2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ryan, A., Rudel, R., Kuchenbecker, M., Fahlke, C.
|
|
<strong>A novel alteration of muscle chloride channel gating in myotonia levior.</strong>
|
|
J. Physiol. 545: 345-354, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12456816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12456816</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12456816[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12456816" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1113/jphysiol.2002.027037" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Steinmeyer1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Steinmeyer, K., Klocke, R., Ortland, C., Gronemeier, M., Jockusch, H., Grunder, S., Jentsch, T. J.
|
|
<strong>Inactivation of muscle chloride channel by transposon insertion in myotonic mice.</strong>
|
|
Nature 354: 304-308, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1659665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1659665</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1659665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/354304a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Steinmeyer1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Steinmeyer, K., Lorenz, C., Pusch, M., Koch, M. C., Jentsch, T. J.
|
|
<strong>Multimeric structure of ClC-1 chloride channel revealed by mutations in dominant myotonia congenita (Thomsen).</strong>
|
|
EMBO J. 13: 737-743, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8112288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8112288</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8112288" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/j.1460-2075.1994.tb06315.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Suetterlin2022" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Suetterlin, K., Matthews, E., Sud, R., McCall, S., Fialho, D., Burge, J., Jayaseelan, D., Haworth, A., Sweeney, M. G., Kullmann, D. M., Schorge, S., Hanna, M. G., Mannikko, R.
|
|
<strong>Translating genetic and functional data into clinical practice: a series of 223 families with myotonia.</strong>
|
|
Brain 145: 607-620, 2022.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34529042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34529042</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34529042[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34529042" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/brain/awab344" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Sun2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sun, C., Tranebjaerg, L., Torbergsen, T., Holmgren, G., Van Ghelue, M.
|
|
<strong>Spectrum of CLCN1 mutations in patients with myotonia congenita in northern Scandinavia.</strong>
|
|
Europ. J. Hum. Genet. 9: 903-909, 2001. Note: Erratum: Europ. J. Hum. Genet. 18: 264 only, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11840191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11840191</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11840191" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.ejhg.5200736" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Thomasen1948" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Thomasen, E.
|
|
<strong>Myotonia, Thomsen's disease. Paramyotonia, and dystrophia myotonica.</strong>
|
|
Op. Ex Domo Biol. Hered. Hum. U. Hafniensis 17: 11-251, 1948.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Thomsen1876" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Thomsen, J.
|
|
<strong>Tonische Kraempfe in willkuerlich beweglichen Muskeln in Folge von ererbter psychischer Disposition: Ataxia muscularis?</strong>
|
|
Arch. Psychiat. Nervenkr. 6: 702-718, 1876.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Vindas-Smith2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vindas-Smith, R., Fiore, M., Vasquez, M., Cuenca, P., del Valle, G., Lagostena, L., Gaitan-Penas, H., Estevez, R., Pusch, M., Morales, F.
|
|
<strong>Identification and functional characterization of CLCN1 mutations found in nondystrophic myotonia patients.</strong>
|
|
Hum. Mutat. 37: 74-83, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26510092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26510092</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26510092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.22916" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Wollnik1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wollnik, B., Kubisch, C., Steinmeyer, K., Pusch, M.
|
|
<strong>Identification of functionally important regions of the muscular chloride channel CIC-1 by analysis of recessive and dominant myotonic mutations.</strong>
|
|
Hum. Molec. Genet. 6: 805-811, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9158157/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9158157</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9158157" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/6.5.805" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Wu2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wu, H., Olson, E. N.
|
|
<strong>Activation of the MEF2 transcription factor in skeletal muscles from myotonic mice.</strong>
|
|
J. Clin. Invest. 109: 1327-1333, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12021248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12021248</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12021248[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12021248" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI15417" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Zhang2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhang, J., Sanguinetti, M. C., Kwiecinski, H., Ptacek, L. J.
|
|
<strong>Mechanism of inverted activation of ClC-1 channels caused by a novel myotonia congenita mutation.</strong>
|
|
J. Biol. Chem. 275: 2999-3005, 2000.
|
|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10644771/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10644771</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10644771" 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.275.4.2999" target="_blank">Full Text</a>]
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<a id="contributors" class="mim-anchor"></a>
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 05/27/2022
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 6/16/2015<br>Cassandra L. Kniffin - updated : 3/11/2013<br>Cassandra L. Kniffin - updated : 10/27/2009<br>Cassandra L. Kniffin - updated : 6/20/2005<br>Patricia A. Hartz - updated : 5/4/2004<br>Victor A. McKusick - updated : 2/6/2003<br>Patricia A. Hartz - updated : 10/8/2002<br>Stylianos E. Antonarakis - updated : 9/10/2002<br>Michael B. Petersen - updated : 8/19/2002<br>Victor A. McKusick - updated : 4/12/2002<br>Ada Hamosh - updated : 1/17/2002<br>Kathryn R. Wagner - updated : 8/6/2001<br>Ada Hamosh - updated : 1/9/2001<br>Ada Hamosh - updated : 2/11/2000<br>Victor A. McKusick - updated : 5/6/1998<br>Victor A. McKusick - updated : 6/23/1997<br>Victor A. McKusick - updated : 5/16/1997<br>Victor A. McKusick - updated : 4/21/1997<br>Orest Hurko - updated : 3/9/1996
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</span>
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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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Victor A. McKusick : 9/29/1992
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</span>
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</div>
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<a id="editHistory" class="mim-anchor"></a>
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 06/01/2022
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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 : 05/27/2022<br>carol : 11/22/2019<br>carol : 11/21/2019<br>carol : 06/21/2019<br>alopez : 10/12/2016<br>alopez : 02/24/2016<br>carol : 6/26/2015<br>mcolton : 6/17/2015<br>ckniffin : 6/16/2015<br>mgross : 10/7/2013<br>alopez : 3/12/2013<br>ckniffin : 3/11/2013<br>ckniffin : 10/31/2011<br>wwang : 11/16/2009<br>ckniffin : 10/27/2009<br>terry : 6/23/2006<br>carol : 6/23/2006<br>carol : 6/29/2005<br>ckniffin : 6/20/2005<br>terry : 3/14/2005<br>mgross : 5/4/2004<br>carol : 2/11/2003<br>tkritzer : 2/11/2003<br>terry : 2/6/2003<br>mgross : 10/8/2002<br>mgross : 9/10/2002<br>mgross : 9/10/2002<br>mgross : 9/10/2002<br>alopez : 8/19/2002<br>alopez : 8/19/2002<br>alopez : 4/25/2002<br>cwells : 4/22/2002<br>terry : 4/12/2002<br>alopez : 1/22/2002<br>terry : 1/17/2002<br>carol : 8/6/2001<br>carol : 8/6/2001<br>mgross : 1/10/2001<br>terry : 1/9/2001<br>alopez : 2/15/2000<br>terry : 2/11/2000<br>carol : 11/9/1999<br>carol : 7/7/1999<br>carol : 6/8/1998<br>carol : 5/12/1998<br>terry : 5/6/1998<br>mark : 7/9/1997<br>alopez : 6/27/1997<br>terry : 6/23/1997<br>terry : 6/18/1997<br>mark : 6/9/1997<br>terry : 6/5/1997<br>terry : 6/5/1997<br>mark : 5/16/1997<br>terry : 5/10/1997<br>terry : 5/6/1997<br>jenny : 4/21/1997<br>terry : 4/14/1997<br>mark : 2/23/1997<br>mark : 12/18/1996<br>jamie : 12/6/1996<br>terry : 12/4/1996<br>terry : 4/15/1996<br>mark : 3/9/1996<br>terry : 2/23/1996<br>mark : 2/22/1996<br>terry : 2/19/1996<br>mark : 1/19/1996<br>mark : 12/18/1995<br>joanna : 12/15/1995<br>mark : 12/15/1995<br>mark : 12/15/1995<br>terry : 12/14/1995<br>terry : 12/13/1995<br>terry : 10/30/1995<br>mark : 9/7/1995<br>carol : 1/23/1995<br>jason : 7/27/1994<br>carol : 12/20/1993<br>carol : 4/29/1993
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<span class="mim-font">
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<strong>*</strong> 118425
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<div>
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<h3>
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<span class="mim-font">
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CHLORIDE CHANNEL 1, SKELETAL MUSCLE; CLCN1
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</h3>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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CHLORIDE CHANNEL, MUSCLE; CLC1
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</span>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: CLCN1</em></strong>
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</span>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 20305008, 57938005, 726051002, 8960007;
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<strong>ICD10CM:</strong> G71.12;
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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: 7q34
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Genomic coordinates <span class="small">(GRCh38)</span> : 7:143,316,111-143,352,083 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<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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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<tbody>
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<td rowspan="3">
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<span class="mim-font">
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7q34
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<td>
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<span class="mim-font">
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Myotonia congenita, dominant
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</td>
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<td>
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<span class="mim-font">
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160800
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</td>
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<td>
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<span class="mim-font">
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3
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</td>
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<td>
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<span class="mim-font">
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Myotonia congenita, recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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255700
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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<tr>
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<td>
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<span class="mim-font">
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Myotonia levior
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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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160800
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The muscle chloride channel CLCN1 regulates the electric excitability of the skeletal muscle membrane. Skeletal muscle has an unusually high resting Cl(-) conductance and in vitro studies suggest that reduction of this conductance causes electrical instability and resulting myotonia in both humans and animal models. Muscle Cl(-) conductance is predominantly mediated by the CLCN1 chloride channel (summary by Steinmeyer et al., 1994). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By homology screening with the major rat skeletal muscle chloride channel CLCN1, Koch et al. (1992) cloned a partial human CLCN1 cDNA that covered about 80% of the coding sequence. This region was 88% identical to the rat channel in amino acid sequence. </p><p>Chen et al. (2013) found expression of the CLCN1 gene in various human brain regions, including cerebellum, hippocampus, spinal cord, and cerebral cortex, as well as in heart. Clcn1 was also expressed in the brain and heart of developing and adult mice. In mouse brain, neuronal expression of Clcn1 was detected in the pyramidal and dentate granule cells of the hippocampus, cerebellar Purkinje cells, scattered brainstem nuclei, frontal neocortex, and thalamus. The results suggested that CLCN1 has a role in neuronal function and excitability in addition to its known role in skeletal muscle. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Steinmeyer et al. (1994) determined that CLCN1 functions as a homooligomer, most likely with 4 subunits. </p><p>Pusch et al. (1995) used a Xenopus transfection to demonstrate shifting of the gating of CLCN1 toward positive voltages by 4 different mutations identified in patients with myotonia congenita (160800). When these mutant cDNAs were coexpressed with wildtype subunits, they imposed altered voltage dependence on the heteromeric channels which would then open only in a voltage range where they could not contribute significantly to the repolarization of action potentials. Without such repolarizations, sodium channels have enough time to recover from inactivation leading to typical myotonic runs, which are a series of repetitive action potentials. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Biochemical Features</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Cryoelectron Microscopy</em></strong></p><p>
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Mindell et al. (2001) reported the formation of 2-dimensional crystals of the prokaryotic CLC channel homolog EriC reconstituted into phospholipid bilayer membranes. Cryoelectron microscopic analysis of these crystals yielded a projection structure at 6.5-angstrom resolution that showed off-axis water-filled pores within the dimeric channel complex. </p><p><strong><em>Crystal Structure</em></strong></p><p>
|
|
Dutzler et al. (2002) presented the x-ray structures of 2 prokaryotic CLC chloride channels, from Salmonella typhimurium and E. coli, at 3.0 and 3.5 angstroms, respectively. Both structures revealed 2 identical pores, each pore being formed by a separate subunit contained within a homodimeric membrane protein. </p><p>Using the 3-dimensional crystal structure of a bacterial CLC protein to predict residues involved in chloride channel inhibitor binding, Estevez et al. (2003) identified an inhibitor-binding site in human CLCN1. The binding site is localized close to the chloride-binding site and is accessible only from the intracellular side. Estevez et al. (2003) concluded that the structures of bacterial CLCs can be extrapolated with fidelity to mammalian chloride channels. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Lorenz et al. (1994) showed that the protein coding sequence of the CLCN1 gene is organized into 23 exons. Its upstream region contains a canonical TATA box, several consensus binding sites for myogenic transcription factors, and 2 other putative regulatory elements. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Mapping</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By blot hybridization to a panel of chromosome 7-specific, human-mouse somatic cell hybrids, Koch et al. (1992) mapped the CLCN1 gene to 7q32-qter. With RFLPs in the CLCN1 gene, they demonstrated that the locus is linked to the T-cell receptor beta locus (see 186930) at 7q35 (maximum lod = 5.23 at theta = 0.0). In the mouse, it had previously been demonstrated that the corresponding loci are linked on chromosome 6, which shows other evidence of homology of synteny to human 7q (Steinmeyer et al., 1991). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Myotonia Congenita</em></strong></p><p>
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In 3 brothers, born of consanguineous parents, with autosomal recessive myotonia congenita (Becker disease; 255700), Koch et al. (1992) identified a homozygous mutation in the CLCN1 gene (F413C; 118425.0001). In affected members of 3 unrelated families with autosomal dominant myotonia congenita (Thomsen disease; 160800), George et al. (1993) identified a heterozygous mutation in the CLCN1 gene (G230E; 118425.0002). The findings indicated that the 2 disorders are allelic. </p><p>Meyer-Kleine et al. (1995) identified 15 different mutations in the CLCN1 gene, of which 10 were novel, in a total of 17 unrelated families and 13 single patients with Becker-type myotonia congenita. One additional family had the dominant Thomsen form. Three mutations accounted for 32% of the Becker chromosomes in the German population; F413C, R894X (118425.0015), and a 14-bp deletion in exon 13 (118425.0009). Although a 437A-T transversion had been described as a disease-causing mutation (Koty et al., 1994), Meyer-Kleine et al. (1995) observed it in 3 myotonia families and in 5 of 200 control chromosomes, consistent with a polymorphism. Moreover, mutant 437A-T cRNA was functionally expressed in Xenopus oocytes and found to induce currents that were indistinguishable from wildtype currents. </p><p>In a screening of 6 unrelated patients with recessive Becker-type myotonia, Mailander et al. (1996) identified 4 novel CLCN1 mutations and a previously reported 14-bp deletion. Five patients were homozygous and the sixth patient was compound heterozygous. Heterozygous carriers of the Becker mutation did not display any clinical symptoms of myotonia; however, all heterozygous males, but none of the heterozygous females, exhibited myotonic discharges on EMG, suggesting a gene-dosage effect of the mutations on chloride conductance and a male predominance of subclinical myotonia. </p><p>Wollnik et al. (1997) analyzed the effect of 1 dominant and 3 recessive mutations in the CLCN1 gene after functional expression in Xenopus oocytes. </p><p>Esteban et al. (1998) stated that 31 specific mutations in the CLCN1 gene had been related to myotonia congenita in humans and 3 in mice. They described a homozygous arg317-to-gln (R317Q; 118425.0011) mutation in affected members of a family with autosomal recessive myotonia congenita. A heterozygous brother had mild muscle stiffness consistent with latent myotonia. The parents were unaffected, although only the mother, who was heterozygous, was available for DNA study. The same R317Q mutation had previously been identified in a family with dominant Thomsen myotonia congenita. At least 2 other mutations, G230E (118425.0002) and R894X, had been found in both dominant and recessive myotonia congenita, depending on the particular family. </p><p>Kubisch et al. (1998) identified 4 novel missense mutations in the CLCN gene, 2 in the dominant form and 2 in the recessive form of myotonia. The first 2 displayed a classic dominant phenotype with a dominant-negative effect by significantly imparting a voltage shift on mutant/wildtype heteromeric channels as found in heterozygous patients. One of the recessive mutations also shifted the voltage dependence to positive values, but coexpression with wildtype CLCN1 gave almost wildtype currents. The voltage dependence of mutant heteromeric channels was not always intermediate between those of the constituent homomeric channel subunits. These complex interactions correlated clinically with various inheritance patterns, ranging from autosomal dominant with various degrees of penetrance to autosomal recessive. </p><p>In affected members of 18 unrelated families from Norway and Sweden with both autosomal dominant (5 families) and autosomal recessive (13 families) inheritance of myotonia congenita, Sun et al. (2001) identified 8 different mutations (1 nonsense, 4 missense, and 3 splice mutations) in the CLCN1 gene; 3 mutations were novel. Fifteen patients had mutations on both alleles, consistent with the recessive disorder; 2 probands had mutations in a single allele; and 2 probands had no CLCN1 mutations. In 2 families, 3 CLCN1 mutations were found in the proband, and Sun et al. (2001) suspected that this phenomenon may be underestimated because mutation search in a disease gene usually ends by the identification of 2 mutations in a family with recessive inheritance. Families with apparently dominant segregation of myotonia congenita may actually represent recessive inheritance with undetected heterozygous individuals married-in as a consequence of a high population carrier frequency of some mutations. The findings, together with the very variable clinical presentation, challenged the classification into dominant Thomsen or recessive Becker disease. Sun et al. (2001) suggested that most cases of myotonia congenita show recessive inheritance with some modifying factors or genetic heterogeneity. </p><p>In a review, Pusch (2002) stated that more than 60 CLCN1 mutations had been identified as causing myotonia, with only a few of them being dominant. A dominant-negative effect of mutant subunits in mutant-wildtype heterodimers was suggested as the usual mechanism for dominant mutations. </p><p>Duno et al. (2004) reported 4 unrelated families with myotonia congenita and the R894X mutation: 2 families had a single mutant allele, showing dominant inheritance, and 2 families were compound heterozygous for R894X and another mutation, showing recessive inheritance. RT-PCR did not reveal any association between total CLCN1 mRNA in muscle and the mode of inheritance, but the dominant family with the most severe phenotype expressed twice the expected amount of the R894X mRNA allele, even compared to the recessive families. Duno et al. (2004) suggested that variation in allelic expression may be a modifier of disease expression and progression in myotonia congenita. </p><p>Raja Rayan et al. (2012) performed multiplex ligation-dependent probe amplification (MLPA) specific to the CLCN1 gene in 60 families with recessive myotonia congenita in whom either no mutations or only a single pathogenic CLCN1 mutation had been identified. The results were positive in 4 (6.7%) patients: 2 unrelated patients were found to have 2 different multiexon deletions within the CLCN1 gene on the second allele, and 2 additional patients had a homozygous duplication of exons 8 through 14 of the CLCN1 gene (118425.0020). The 2 patients with the duplication were both of Iraqi origin, but were unrelated. Both Iraqi patients had a severe form of the disorder with onset in infancy. Haplotype analysis suggested a founder effect for this duplication mutation. Raja Rayan et al. (2012) concluded that copy number variation involving the CLCN1 gene is an important genetic mechanism in patients with recessive myotonia congenita, and that MLPA analysis may aid in genetic counseling. </p><p>In 4 Costa Rican families with myotonia congenita, Vindas-Smith et al. (2016) identified mutations in the CLCN1 gene by bidirectional sequencing of the CLCN1 gene, with confirmation by RFLP-PCR. In 2 families in which the proband had Thomsen disease (families 1 and 4), heterozygous mutations were identified (F167L; Q412P, 118425.0022). In another family in which the proband had Thomsen disease (family 2), compound heterozygous mutations were identified (R105C and F167L). In a proband (family 3) with a myositis-like disorder, a variant of unknown significance (Q154R) was identified. Functional studies of CLCN1 with the F167L, R105C, or Q154R mutation did not show alterations of gating parameters or channel conductance. Functional studies of CLCN1 with the Q412P mutation expressed in Xenopus oocytes showed reduced surface expression and reduced current density. Vindas-Smith et al. (2016) concluded that the Q412P mutation induces a severe folding defect that leads to its degradation before it can dimerize with the wildtype subunit. </p><p>Altamura et al. (2018) evaluated the functional significance of 7 mutations in the C-terminal region of the CLCN1 gene associated with either autosomal dominant Thomsen disease or autosomal recessive Becker disease. CLCN1 with each mutation was transfected into HEK293 cells and analyzed with patch-clamp analysis. Five of the mutations were in the CBS2 domain (V829M, T832I, V851M, G859V, L861P) and 2 of the mutations were in the C-terminal peptide (P883T, V947E). Mutations located between residues 829 and 835 and in residue 883 resulted in alteration of voltage dependence. Mutations between residues 851 and 859 and in residue 947 resulted in a reduction of chloride currents. The results were consistent with a role for CBS2 in protein channel gating and demonstrated the importance of the C-peptide region in protein function and expression. </p><p>Suetterlin et al. (2022) assessed the function of 95 CLCN1 mutations, including 34 novel mutations, identified in 233 patients with myotonia congenita. Mutations in CLCN1 were assessed by transfection of cDNA with each mutation into Xenopus laevis oocytes and analyzed with 2-electrode voltage clamp assays. From a functional standpoint, mutations that altered voltage dependence of activation clustered in the first half of the transmembrane domains and mutations resulting in absent currents clustered in the second half of the transmembrane domain. In terms of assessment of clinical significance and inheritance patterns, mutations that resulted in dominant functional features clustered in the TM1 domain, and variants associated with recessive functional features and without a shift in voltage dependence of activation were clustered in the TM2 domain. Mutations in the intracellular domain were not associated with a dominant inheritance pattern. Suetterlin et al. (2022) concluded that functional characterization of CLCN1 mutations improves the assessment of their clinical implications. </p><p><strong><em>Myotonic Dystrophy</em></strong></p><p>
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Myotonic dystrophy (DM1; 160900) is caused by a trinucleotide repeat expansion of the DMPK gene (605377.0001). In DM, expression of RNAs that contain expanded CUG or CCUG repeats is associated with degeneration and repetitive action potentials (myotonia) in skeletal muscle. Using skeletal muscle from a transgenic mouse model of DM, Mankodi et al. (2002) showed that expression of expanded CUG repeats reduced the transmembrane chloride conductance to levels well below those expected to cause myotonia. The expanded CUG repeats triggered aberrant splicing of pre-mRNA for CLCN1, resulting in loss of the CLCN1 protein from the surface membrane. Mankodi et al. (2002) identified a similar defect in CLCN1 splicing and expression in DM1 and DM2 (602668). The authors proposed that a transdominant effect of mutant RNA on CLCN1 RNA processing leads to chloride channelopathy and membrane hyperexcitability in DM. </p><p>Charlet-B et al. (2002) demonstrated loss of CLCN1 mRNA and protein in DM1 skeletal muscle tissue due to aberrant splicing of the CLCN1 pre-mRNA. They showed that the splicing regulator, CUG-binding protein (CUGBP; 601074), which is elevated in DM1 striated muscle, bound to the CLCN1 pre-mRNA, and that overexpression of CUGBP in normal cells reproduced the aberrant pattern of CLCN1 splicing observed in DM1 skeletal muscle. Charlet-B et al. (2002) proposed that disruption of alternative splicing regulation causes a predominant pathologic feature of DM1. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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See 118425.0021 for discussion of a possible association between variation in the CLCN1 gene and idiopathic generalized epilepsy (EIG; see 600669).</p>
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</span>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Genotype/Phenotype Correlations</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Aminoff et al. (1977) found that a subset of patients with myotonia congenita showed a marked decrement of the compound motor action potential (CMAP) with repeated stimulation compared to controls. Although the presence of decrement was not related to the degree of myotonia, it was usually observed in patients with autosomal recessive disease. Colding-Jorgensen et al. (2003) found that all 6 patients with the dominant P480L (118425.0006) mutation had CMAP decrements above 30%. In patients with the R894X (118425.0015) mutation, some had a large decrement, some had a slight decrement, and some had no change. Two patients with 2 CLCN1 mutations, 1 of whom carried an R894X mutation, had large decrements above 80%. Presence of decrement did not correlate with disease severity. Colding-Jorgensen et al. (2003) concluded that CMAP decrement may occur in dominant myotonia congenita and likely reflects the degree of chloride conduction reduction caused by particular mutations. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The Adr ('arrested development of righting') mouse, a model of autosomal recessive myotonia congenita, was found to be due to a mutation on mouse chromosome 6 (Rudel, 1990) in a region of the genome with homology of synteny to human chromosome 7q31-q35. The locus in the mouse is between those for Tcrb and Hox1. Steinmeyer et al. (1991) found that the Adr mouse phenotype was caused by a transposon insertion mutation that altered and inactivated the muscle-membrane chloride channel gene. The findings confirmed that the Adr mouse is an authentic model of Becker disease in the human. </p><p>Wu and Olson (2002) determined that Adr mice, which have an inactivated Clcn1 gene, showed an increased number of oxidative fibers, lacked glycolytic fibers, and showed muscle hypertrophy, similar to patients with Becker syndrome. By breeding Clcn1-null mice with mice harboring an Mef2 (600660)-dependent reporter gene, they found that the transcriptional activity of Mef2 was dramatically enhanced in myotonic muscle. Induction of Mef2 did not correlate with enhanced DNA-binding activity, but did correlate with activation of p38 Mapk (see 600289), an activator of Mef2, and with reduced expression of class II histone deacetylases (HDACs; see 605314), which repress Mef2 activity. Wu and Olson (2002) hypothesized that mutations in Clcn1 alter intracellular calcium levels, leading to the combined effects of class II Hdac deficiency and p38 Mapk activation, resulting in upregulation of Mef2 transcriptional activity followed by long-term changes in gene expression and to fiber-type transformation. </p><p>Beck et al. (1996) noted that the current hypotheses regarding the pathophysiology of autosomal dominant myotonia congenita, or Thomsen disease, were initially formulated from studies of the myotonic goat, an unusual breed afflicted with severe autosomal dominant congenital myotonia that closely resembles the human disease clinically and in its mode of inheritance. These animals are often referred to as 'fainting,' 'nervous,' 'stiff-legged,' or 'epileptic' goats because of their tendency to develop severe acute muscle stiffness and become immobile and often fall when attempting to make sudden forceful movements or when startled. The pathogenesis of myotonia in the goat was elucidated by Bryant and colleagues (Bryant, 1962, Lipicky and Bryant, 1966) who first described a severely diminished resting chloride conductance in muscle fibers from affected animals. The same group (Adrian and Bryant, 1974) also demonstrated that myotonia could be produced in normal skeletal muscle fibers bathed in a chloride-free solution. Beck et al. (1996) demonstrated the molecular basis for the decreased muscle chloride conductance in this historically important animal model. They found a single nucleotide change (GCC to CCC), resulting in an ala885-to-pro (A885P) substitution in a conserved residue in the C terminus of the goat muscle chloride channel, 104 residues from the termination codon. Heterologous expression of the mutation demonstrated a substantial (+47 mV) shift in the midpoint of steady-state activation of the channel, resulting in a diminished channel open probability at voltages near the resting membrane potential of skeletal muscle. </p>
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</span>
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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>22 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 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CLCN1, PHE413CYS
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<br />
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SNP: rs121912799,
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gnomAD: rs121912799,
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ClinVar: RCV000019083, RCV000184008, RCV000346725, RCV000638232, RCV001548747, RCV002291268
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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 brothers with autosomal recessive generalized myotonia congenita (Becker disease; 255700), born of consanguineous parents, Koch et al. (1992) identified a homozygous T-to-G transversion in the CLCN1 gene, resulting in a phe413-to-cys (F413C) substitution toward the end of putative membrane span D8. This residue lies in a highly conserved region of the channel protein that is predicted to form a membrane-spanning alpha helix and possibly a component of the permeation pore (George et al., 1993). </p><p>Koch et al. (1993) found the F413C missense mutation in 15% of chromosomes carrying a gene for recessive myotonia congenita. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 MYOTONIA CONGENITA, AUTOSOMAL DOMINANT</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CLCN1, GLY230GLU
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<br />
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SNP: rs80356700,
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gnomAD: rs80356700,
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ClinVar: RCV000019084, RCV000020113, RCV000291823, RCV000627758, RCV003317041, RCV004532391
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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 affected members of 3 unrelated families with autosomal dominant myotonia congenita (Thomsen disease; 160800), George et al. (1993) identified a G-to-A transition in the CLCN1 gene, resulting in a gly230-to-glu (G230E) substitution between the third and fourth predicted membrane-spanning segments. This glycine residue is conserved in all known members of this class of chloride channel proteins. The codon number used for this mutation was based on the available partial-length cDNA of CLCN1; when the full-length cDNA became known, the codon number was changed from 180 to 230 (George, 1997). </p><p>In functional expression studies, Fahlke et al. (1997) found that the G230E mutation caused substantial changes in anion and cation selectivity, as well as a fundamental change in rectification of the current-voltage relationship. Whereas wildtype channels were characterized by pronounced inward rectification and a characteristic pattern of selectivity, G230E exhibited outward rectification at positive potentials and a different pattern of selectivity. Furthermore, the cation-to-anion permeability ratio of the mutant was much greater than that of the wildtype channel. </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 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CLCN1, IVSDS, G-A, +1
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<br />
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SNP: rs1563078827,
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ClinVar: RCV000019086
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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 affected members of a German family with recessive myotonia (255700), Lorenz et al. (1994) identified compound heterozygosity for 2 mutations in the CLCN1 gene: a 979G-A transition in a splice consensus site at the end of exon 8, and a 1488G-T transversion in exon 14, resulting in an arg496-to-ser (R496S; 118425.0004). Functional expression of R496S cRNA in Xenopus oocytes yielded no detectable currents. Furthermore, it did not suppress wildtype currents in coexpression assay, confirming it as a recessive mutation. The G-to-A transition in exon 8 was stated to affect the last nucleotide of the exon. If this interfered with mRNA splicing at that exon/intron boundary, the translation product would be terminated by a stop codon after 51 additional amino acids or other splice sites in the intron might be used. Alternatively, if splicing were normal, this mutation would lead to a substitution of isoleucine for valine at position 327 (V327I). Since this residue is not conserved among the members of this gene family and most members have negatively charged glutamate residues at this position, it is unlikely that such a substitution would have a dramatic effect on channel function. This would argue for an aberrant splicing as the effect of the G979A 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 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CLCN1, ARG496SER
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<br />
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SNP: rs121912801,
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gnomAD: rs121912801,
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ClinVar: RCV000019087, RCV000692794, RCV001781281, RCV004532392
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the arg496-to-ser (R496S) mutation in the CLCN1 gene that was found in compound heterozygous state in affected members of a family with recessive myotonia (255700) by Lorenz et al. (1994), see 118425.0003. </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>.0005 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CLCN1, GLY482ARG
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<br />
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SNP: rs746125212,
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gnomAD: rs746125212,
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ClinVar: RCV000019088, RCV000657922, RCV000810078, RCV003764473, RCV003989574
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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 affected members of a family with Becker myotonia congenita (255700), Koch et al. (1994) identified a mutation in the CLCN1 gene, resulting in a gly482-to-arg (G482R) substitution. Interestingly, this mutation producing a recessive phenotype is only 2 codons removed from a pro480-to-leu (P480L; 118425.0006) mutation which results in the dominant Thomsen type of myotonia congenita.</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 MYOTONIA CONGENITA, AUTOSOMAL DOMINANT</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CLCN1, PRO480LEU
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<br />
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SNP: rs80356694,
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gnomAD: rs80356694,
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ClinVar: RCV000019089, RCV000020101, RCV001237767
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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 affected members of Thomsen's own family (Thomsen, 1876; Thomasen, 1948) with autosomal dominant myotonia congenita (160800), Steinmeyer et al. (1994) identified a heterozygous mutation in the CLCN1 gene, resulting in a pro480-to-leu (P480L) substitution. Functional expression studies showed that the P480L mutation dramatically inhibited normal CLCN1 channel function via a dominant-negative effect. </p><p>Koch et al. (1994) also reported the P480L mutation as causative of Thomsen disease.</p><p>Pusch et al. (1995) transfected cDNA bearing the P480L mutation into Xenopus oocytes, demonstrating a large 90-mV shift of the gating toward positive voltages. In further structure studies, they replaced isoleucine 290 by 18 different amino acids. Substitution with valine shifted the gating by -17 millivolts. In all other replacements, the gating was either shifted to more positive voltages or resulted in no current above background. </p><p>Colding-Jorgensen et al. (2003) found that all 6 patients with the dominant P480L mutation had CMAP decrements above 30%, which the authors suggested was correlated with the large voltage shift conferred by the mutation. </p>
|
|
</span>
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|
</div>
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<div>
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|
<br />
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|
</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0007 MYOTONIA LEVIOR</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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CLCN1, GLN552ARG
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<br />
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SNP: rs80356696,
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|
gnomAD: rs80356696,
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|
|
ClinVar: RCV000019090, RCV000020103, RCV000498537, RCV000685420, RCV001253100
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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 brothers with a mild form of dominant myotonia, referred to as myotonia levior (see 160800), Lehmann-Horn et al. (1995) identified a 1655A-G transition in exon 15 of the CLCN1 gene, resulting in a gln552-to-arg (Q552R) substitution. Their affected mother also had the mutation. The findings indicated that myotonia levior is a variant or allelic form of Thomsen disease. </p><p>By functional expression studies, Ryan et al. (2002) demonstrated that CLCN1 channels with the Q552R mutation were formed normally, but had altered gating properties. Voltage dependence of the mutant channels was shifted by more than +90 mV compared to wildtype channels, resulting in a reduction in the open probability of the channel. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0008 MYOTONIA CONGENITA, AUTOSOMAL DOMINANT</strong>
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</span>
|
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CLCN1, ILE290MET
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<br />
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SNP: rs80356690,
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gnomAD: rs80356690,
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ClinVar: RCV000019091, RCV000020117, RCV000626584, RCV000690053, RCV000711241, RCV001196224, RCV004528125
|
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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 affected members of a family with Thomsen myotonia (160800), Lehmann-Horn et al. (1995) identified an 870C-G transversion in the CLCN1 gene, resulting in an ile290-to-met (I290M) substitution. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
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</div>
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</div>
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<div>
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<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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CLCN1, 14-BP DEL
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<br />
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SNP: rs768119034,
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gnomAD: rs768119034,
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|
|
ClinVar: RCV000395981, RCV000552780, RCV000664241, RCV000778142, RCV001262336, RCV001753742, RCV002259330, RCV003319191
|
|
|
|
|
|
</span>
|
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</div>
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<div>
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|
<span class="mim-text-font">
|
|
<p>In patients with Becker myotonia (255700), Meyer-Kleine et al. (1994) identified a 14-bp deletion in exon 13 of the CLCN1 gene. </p><p>In a family in which the index patient and his mother had been examined by Becker (1977), who classified their disorder as dominant myotonia congenita, Lehmann-Horn et al. (1995) found that the proband was homozygous for a 14-bp deletion (involving nucleotides 1437-1450) in exon 13 of the CLCN1 gene. Both nonmyotonic sons of the index patient were heterozygous for the deletion. </p><p>In French Canadian patients with recessive myotonia, Dupre et al. (2009) found that homozygosity for the 14-bp deletion resulted in a severe phenotype with generalized hypertrophy, moderate myotonia, and transient weakness. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
|
|
</div>
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|
|
</div>
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|
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|
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|
<div>
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
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|
|
|
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<div>
|
|
<span class="mim-text-font">
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|
|
|
CLCN1, GLU291LYS
|
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|
<br />
|
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|
|
SNP: rs121912805,
|
|
|
|
|
|
gnomAD: rs121912805,
|
|
|
|
|
|
ClinVar: RCV000019093, RCV001041229, RCV001781282, RCV002468557
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs with autosomal recessive myotonia congenita (255700), Pusch et al. (1995) identified compound heterozygosity for 2 mutations in the CLCN1 gene: glu291-to-lys (E291K) and arg894-to-ter (R894X; 118425.0015). Functional expression studies showed that the E291K channels did not yield currents between -140 and 100 millivolts, indicating that this mutation totally abolished channel activity. In contrast to the mutation in the neighboring amino acid (I290M; 118425.0008), which acts as a dominant as a result of interactions with wildtype monomers, the E291K mutation is recessive. Whereas the I290M mutant shifts the voltage dependence of chloride channels positive (via homomers or heteromers with wildtype subunits), the E291K mutation shows no evidence of interaction and does not shift the voltage dependence. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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|
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|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
MYOTONIA CONGENITA, AUTOSOMAL DOMINANT, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLCN1, ARG317GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80356702,
|
|
|
|
|
|
gnomAD: rs80356702,
|
|
|
|
|
|
ClinVar: RCV000019094, RCV000019095, RCV000020121, RCV000516960, RCV000626585, RCV000763169
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>The arg317-to-gln (R317Q) mutation illustrates the resultant occurrence of either autosomal dominant myotonia congenita (160800) or autosomal recessive myotonia congenita (255700), depending on the family background. Meyer-Kleine et al. (1995) observed the R317Q mutation in dominant Thomsen myotonia congenita; Esteban et al. (1998) observed it in Becker myotonia congenita and pointed to other mutations that had been observed as a recessive or a dominant, depending on the particular family. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLCN1, GLY499ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121912807,
|
|
|
|
|
|
gnomAD: rs121912807,
|
|
|
|
|
|
ClinVar: RCV000019096, RCV001382414
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with Becker myotonia congenita (255700), Zhang et al. (2000) identified a C-to-T transition at codon 1495 in exon 14 of the CLCN1 gene, resulting in a gly499-to-arg (G499R) substitution in the putative transmembrane domain 10 of the CLCN1 protein. In contrast to normal CLCN1 channels that deactivate upon hyperpolarization, functional expression of G499R CLCN1 yielded a hyperpolarization-activated chloride current when measured in the presence of a high intracellular chloride concentration. Current was abolished when measured with a physiologic chloride transmembrane gradient. Electrophysiologic analysis of other gly449 mutants suggested that the positive charge introduced by the G499R mutation may be responsible for this unique gating behavior. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLCN1, 1-BP INS, 831G
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs140026363,
|
|
|
|
|
|
gnomAD: rs140026363,
|
|
|
|
|
|
ClinVar: RCV000019097, RCV001382411
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 African American sibs with autosomal recessive myotonia congenita (255700), Nagamitsu et al. (2000) identified compound heterozygosity for 2 mutations in the CLCN1 gene: a 1-bp insertion (831insG) in exon 7, resulting in a premature termination codon at codon 289, and a C-to-T transition in exon 23, resulting in a pro932-to-leu (P932L; 118425.0014) substitution. In addition to generalized myotonia and proximal muscle hypertrophy, the sibs also displayed progressive muscle weakness, joint contractures, and dystrophic muscle pathology. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLCN1, PRO932LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80356706,
|
|
|
|
|
|
gnomAD: rs80356706,
|
|
|
|
|
|
ClinVar: RCV000019085, RCV000020108, RCV000478940, RCV000638250
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the pro932-to-leu (P932L) mutation in the CLCN1 gene that was found in compound heterozygous state in sibs with autosomal recessive myotonia congenita (255700) by Nagamitsu et al. (2000), see 118425.0013. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
MYOTONIA CONGENITA, AUTOSOMAL DOMINANT, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLCN1, ARG894TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs55960271,
|
|
|
|
|
|
gnomAD: rs55960271,
|
|
|
|
|
|
ClinVar: RCV000019098, RCV000019099, RCV000020107, RCV000292791, RCV000626582, RCV000627759, RCV001564017, RCV001794458, RCV001813999, RCV004515784, RCV004737160
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg894-to-ter (R894X) mutation in the CLCN1 gene that was found in compound heterozygous state in sibs with autosomal recessive myotonia congenita (255700) by Pusch et al. (1995), see 118425.0010. </p><p>In patients with both autosomal recessive and autosomal dominant (160800) myotonia congenita, Meyer-Kleine et al. (1995) identified a mutation in the CLCN1 gene, resulting in an R894X substitution. Functional expression of the R894X mutant in Xenopus oocytes revealed a large reduction, but not complete abolition, of chloride currents. Further, it had a weak dominant-negative effect on wildtype currents in coexpression studies. Reduction of currents predicted for heterozygous carriers were close to the borderline value, sufficient to elicit myotonia. </p><p>Sun et al. (2001) found a carrier frequency of 0.87% for the R894X mutation in the northern Scandinavian population. </p><p>In a French Canadian family with myotonia, Dupre et al. (2009) found that the R894X mutation could be expressed in a semidominant or recessive manner. The proband, who was heterozygous for the R894X mutation, had muscle stiffness and mild warm-up phenomenon, but no significant percussion myotonia and no myotonia on EMG. In contrast, her daughters, who were compound heterozygous for the R894X and R300X (118425.0017) mutations, showed a moderately severe phenotype with generalized hypertrophy consistent with autosomal recessive Becker myotonia. This compound heterozygous genotype showed resistance to phenytoin, mexiletine, and quinine. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 MYOTONIA CONGENITA, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLCN1, MET128VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80356699,
|
|
|
|
|
|
|
|
ClinVar: RCV000019100, RCV000020109, RCV001049292
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with autosomal dominant myotonia congenita (160800), Colding-Jorgensen et al. (2003) identified a heterozygous A-to-G transition in the CLCN1 gene, resulting in a met128-to-val (M128V) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLCN1, ARG300TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1586496726,
|
|
|
|
|
|
|
|
ClinVar: RCV000019101
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg300-to-ter (R300X) mutation in the CLCN1 gene that was found in compound heterozygous state in patients with autosomal recessive myotonia congenita (255700) by Dupre et al. (2009), see 118425.0015. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 MYOTONIA CONGENITA, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLCN1, SER189PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121912810,
|
|
|
|
|
|
|
|
ClinVar: RCV000019102, RCV003387727
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 French Canadian women with autosomal dominant myotonia congenita (160800), Dupre et al. (2009) identified a heterozygous ser189-to-phe (S189F) substitution in the CLCN1 gene. Both women had mild fluctuating myotonia and mild muscle hypertrophy and reported aggravation of symptoms with menstrual periods and pregnancy. </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>.0019 MYOTONIA CONGENITA, AUTOSOMAL DOMINANT</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE, 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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CLCN1, TRP433ARG
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<br />
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ClinVar: RCV000019103, RCV000019104
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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>Dupre et al. (2009) identified a heterozygous or homozygous trp433-to-arg (W433R) substitution in the CLCN1 gene in French Canadian patients with autosomal dominant (160800) and recessive (255700) myotonia, respectively. The recessive phenotype was characterized by severe myotonia, dysphagia, generalized hypertrophy predominant in lower limb muscles, and the warm-up phenomenon. </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>.0020 MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CLCN1, DUP, EX8-14
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<br />
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ClinVar: RCV000033240
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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 Iraqi women with severe infantile-onset myotonia congenita (255700), Raja Rayan et al. (2012) identified a homozygous duplication of exons 8 through 14 of the CLCN1 gene, predicted to result in a frameshift. Both patients came from consanguineous families and had multiple affected family members. The duplication was identified by multiplex ligation-dependent probe amplification (MLPA) specific to the CLCN1 gene, and was not found in 124 control chromosomes or in a variant database. Haplotype analysis suggested a founder effect for this duplication mutation. Raja Rayan et al. (2012) concluded that copy number variation involving the CLCN1 gene is an important genetic mechanism in patients with recessive myotonia congenita, and that MLPA analysis may aid in genetic counseling. </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>.0021 VARIANT OF UNKNOWN SIGNIFICANCE</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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CLCN1, ARG976TER
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<br />
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SNP: rs142539932,
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gnomAD: rs142539932,
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ClinVar: RCV000180791, RCV000195160, RCV000535831, RCV003488433
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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>This variant is classified as a variant of unknown significance because its contribution to idiopathic generalized epilepsy (EIG; see 600669) has not been confirmed.</p><p>In a 26-year-old Italian woman with EIG, Chen et al. (2013) identified a de novo heterozygous c.2926C-T transition (c.2926C-T, NM_000083) in exon 23 of the CLCN1 gene, resulting in an arg976-to-ter (R976X) substitution and truncation of the distal C terminus by 12 residues. The mutation, which was found by exome sequencing of 291 patients with epilepsy, was not found in the dbSNP or 1000 Genomes Project databases. The patient had generalized pharmacoresistant epilepsy with mixed seizure types, including generalized tonic-clonic and absence seizures. Her first seizure occurred during a febrile illness at age 11 months. EEG repeatedly showed generalized spike-wave discharges. In addition, she presented with myotonic writer's cramp at age 9 years, which subsequently resolved. EMG as an adult showed no evidence of myotonic discharges. Brain MRI and cognitive function were normal. Functional studies of the variant were not performed, but Chen et al. (2013) found expression of the CLCN1 gene in multiple human brain regions, and suggested that the mutation identified in this patient could result in neuronal hyperexcitability, thus contributing to the seizure phenotype. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0022 MYOTONIA CONGENITA, AUTOSOMAL DOMINANT</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CLCN1, GLN412PRO
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<br />
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SNP: rs1279658001,
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gnomAD: rs1279658001,
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ClinVar: RCV001382412, RCV002251767
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a Costa Rican patient (family 4-CR14) with autosomal dominant myotonia congenita (160800), Vindas-Smith et al. (2016) identified a heterozygous c.1235A-C transversion in exon 11 of the CLCN1 gene, resulting in a gln412-to-pro (Q412P) substitution. The mutation, which was identified by bidirectional sequencing of the CLCN1 gene and confirmed by RFLP-PCR, was also found in the patient's asymptomatic (self-reported) mother and 2 sibs. Functional studies of CLCN1 with the Q412P mutation expressed in Xenopus oocytes showed reduced surface expression and reduced current density but did not display a dominant-negative effect when coexpressed with wildtype CLCN1. </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>
|
|
<p class="mim-text-font">
|
|
Adrian, R. H., Bryant, S. H.
|
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<strong>On the repetitive discharge in myotonic muscle fibres.</strong>
|
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J. Physiol. 240: 505-515, 1974.
|
|
|
|
|
|
[PubMed: 4420758]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1113/jphysiol.1974.sp010620]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Altamura, C., Lucchiari, S., Sahbani, D., Ulzi, G., Comi, G. P., D'Ambrosio, P., Petillo, R., Politano, L., Vercelli, L., Mongini, T., Dotti, M. T., Cardani, R., Meola, G., Lo Monaco, M., Matthews, E., Hanna, M. G., Carratu, M. R., Conte, D., Imbrici, P., Desaphy, J.-F.
|
|
<strong>The analysis of myotonia congenita mutations discloses functional clusters of amino acids within the CBS2 domain and the C-terminal peptide of the CLC-1 channel.</strong>
|
|
Hum. Mutat. 39: 1273-1283, 2018.
|
|
|
|
|
|
[PubMed: 29935101]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.23581]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Aminoff, M. J., Layzer, R. B., Satya-Murti, S., Faden, A. I.
|
|
<strong>The declining electrical response of muscle to repetitive nerve stimulation in myotonia.</strong>
|
|
Neurology 27: 812-816, 1977.
|
|
|
|
|
|
[PubMed: 561337]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.27.9.812]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Beck, C. L., Fahlke, C., George, A. L., Jr.
|
|
<strong>Molecular basis for decreased muscle chloride conductance in the myotonic goat.</strong>
|
|
Proc. Nat. Acad. Sci. 93: 11248-11252, 1996.
|
|
|
|
|
|
[PubMed: 8855341]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.93.20.11248]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Becker, P. E.
|
|
<strong>Myotonia Congenita and Syndromes associated with Myotonia: Clinical-Genetic Studies of the Nondystrophic Myotonias.</strong>
|
|
Stuttgart: Georg Thieme (pub.) 1977.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bryant, S. H.
|
|
<strong>Muscle membrane of normal and myotonic goats in normal and low external chloride. (Abstract)</strong>
|
|
Fed. Proc. 21: 312 only, 1962.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Charlet-B, N., Savkur, R. S., Singh, G., Philips, A. V., Grice, E. A., Cooper, T. A.
|
|
<strong>Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing.</strong>
|
|
Molec. Cell 10: 45-53, 2002.
|
|
|
|
|
|
[PubMed: 12150906]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s1097-2765(02)00572-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, T. T., Klassen, T. L., Goldman, A. M., Marini, C., Guerrini, R., Noebels, J. L.
|
|
<strong>Novel brain expression of ClC-1 chloride channels and enrichment of CLCN1 variants in epilepsy.</strong>
|
|
Neurology 80: 1078-1085, 2013.
|
|
|
|
|
|
[PubMed: 23408874]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/WNL.0b013e31828868e7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Colding-Jorgensen, E., Duno, M., Schwartz, M., Vissing, J.
|
|
<strong>Decrement of compound muscle action potential is related to mutation type in myotonia congenita.</strong>
|
|
Muscle Nerve 27: 449-455, 2003.
|
|
|
|
|
|
[PubMed: 12661046]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/mus.10347]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Duno, M., Colding-Jorgensen, E., Grunnet, M., Jespersen, T., Vissing, J., Schwartz, M.
|
|
<strong>Difference in allelic expression of the CLCN1 gene and the possible influence on the myotonia congenita phenotype.</strong>
|
|
Europ. J. Hum. Genet. 12: 738-743, 2004.
|
|
|
|
|
|
[PubMed: 15162127]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5201218]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dupre, N., Chrestian, N., Bouchard, J.-P., Rossignol, E., Brunet, D., Sternberg, D., Brias, B., Mathieu, J., Puymirat, J.
|
|
<strong>Clinical, electrophysiologic, and genetic study of non-dystrophic myotonia in French-Canadians.</strong>
|
|
Neuromusc. Disord. 19: 330-334, 2009.
|
|
|
|
|
|
[PubMed: 18337100]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.nmd.2008.01.007]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dutzler, R., Campbell, E. B., Cadene, M., Chait, B. T., MacKinnon, R.
|
|
<strong>X-ray structure of a CIC chloride channel at 3.0 angstrom reveals the molecular basis of anion selectivity.</strong>
|
|
Nature 415: 287-294, 2002.
|
|
|
|
|
|
[PubMed: 11796999]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/415287a]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Esteban, J., Neumeyer, A. M., McKenna-Yasek, D., Brown, R. H.
|
|
<strong>Identification of two mutations and a polymorphism in the chloride channel CLCN-1 in patients with Becker's generalized myotonia.</strong>
|
|
Neurogenetics 1: 185-188, 1998.
|
|
|
|
|
|
[PubMed: 10737121]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s100480050027]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Estevez, R., Schroeder, B. C., Accardi, A., Jentsch, T. J., Pusch, M.
|
|
<strong>Conservation of chloride channel structure revealed by an inhibitor binding site in CIC-1.</strong>
|
|
Neuron 38: 47-59, 2003.
|
|
|
|
|
|
[PubMed: 12691663]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0896-6273(03)00168-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fahlke, C., Beck, C. L., George, A. L., Jr.
|
|
<strong>A mutation in autosomal dominant myotonia congenita affects pore properties of the muscle chloride channel.</strong>
|
|
Proc. Nat. Acad. Sci. 94: 2729-2734, 1997.
|
|
|
|
|
|
[PubMed: 9122265]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.94.6.2729]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
George, A. L., Jr., Crackower, M. A., Abdalla, J. A., Hudson, A. J., Ebers, G. C.
|
|
<strong>Molecular basis of Thomsen's disease (autosomal dominant myotonia congenita).</strong>
|
|
Nature Genet. 3: 305-310, 1993.
|
|
|
|
|
|
[PubMed: 7981750]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0493-305]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
George, A. L., Jr.
|
|
<strong>Personal Communication.</strong>
|
|
Nashville, Tenn. 4/14/1997.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koch, M. C., Meyer-Kleine, C., Otto, M., Ricker, K., Lorenz, C., Steinmeyer, K., Jentsch, T. J.
|
|
<strong>Mutations in the CLCN1 gene leading to myotonia congenita Thomsen and generalized myotonia Becker. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 55 (suppl.): A226, 1994.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koch, M. C., Ricker, K., Otto, M., Wolf, F., Zoll, B., Lorenz, C., Steinmeyer, K., Jentsch, T. J.
|
|
<strong>Evidence for genetic homogeneity in autosomal recessive generalised myotonia (Becker).</strong>
|
|
J. Med. Genet. 30: 914-917, 1993.
|
|
|
|
|
|
[PubMed: 8301644]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.30.11.914]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koch, M. C., Steinmeyer, K., Lorenz, C., Ricker, K., Wolf, F., Otto, M., Zoll, B., Lehmann-Horn, F., Grzeschik, K.-H., Jentsch, T. J.
|
|
<strong>The skeletal muscle chloride channel in dominant and recessive human myotonia.</strong>
|
|
Science 257: 797-800, 1992.
|
|
|
|
|
|
[PubMed: 1379744]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1379744]
|
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</p>
|
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</li>
|
|
|
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<li>
|
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<p class="mim-text-font">
|
|
Koty, P. P., Marks, H. G., Turel, A., Flagler, D., Angelini, C., Pegoraro, E., Vancott, A. C., Manchester, D., Zonana, J., Bird, T. D., Hoffman, E. P.
|
|
<strong>Linkage analysis of Thomsen and Becker myotonia families. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 55 (suppl.): A227, 1994.
|
|
|
|
</p>
|
|
</li>
|
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|
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<li>
|
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<p class="mim-text-font">
|
|
Kubisch, C., Schmidt-Rose, T., Fontaine, B., Bretag, A. H., Jentsch, T. J.
|
|
<strong>ClC-1 chloride channel mutations in myotonia congenita: variable penetrance of mutations shifting the voltage dependence.</strong>
|
|
Hum. Molec. Genet. 7: 1753-1760, 1998.
|
|
|
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|
|
[PubMed: 9736777]
|
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|
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|
|
[Full Text: https://doi.org/10.1093/hmg/7.11.1753]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Lehmann-Horn, F., Mailander, V., Heine, R., George, A. L.
|
|
<strong>Myotonia levior is a chloride channel disorder.</strong>
|
|
Hum. Molec. Genet. 4: 1397-1402, 1995.
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|
|
[PubMed: 7581380]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/4.8.1397]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lipicky, R. J., Bryant, S. H.
|
|
<strong>Sodium, potassium, and chloride fluxes in intercostal muscle from normal goats and goats with hereditary myotonia.</strong>
|
|
J. Gen. Physiol. 50: 89-111, 1966.
|
|
|
|
|
|
[PubMed: 5971035]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1085/jgp.50.1.89]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lorenz, C., Meyer-Kleine, C., Steinmeyer, K., Koch, M. C., Jentsch, T. J.
|
|
<strong>Genomic organization of the human muscle chloride channel CLC-1 and analysis of novel mutations leading to Becker-type myotonia.</strong>
|
|
Hum. Molec. Genet. 3: 941-946, 1994.
|
|
|
|
|
|
[PubMed: 7951242]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/3.6.941]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mailander, V., Heine, R., Deymeer, F., Lehmann-Horn, F.
|
|
<strong>Novel muscle chloride channel mutations and their effects on heterozygous carriers.</strong>
|
|
Am. J. Hum. Genet. 58: 317-324, 1996.
|
|
|
|
|
|
[PubMed: 8571958]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mankodi, A., Takahashi, M. P., Jiang, H., Beck, C. L., Bowers, W. J., Moxley, R. T., Cannon, S. C., Thornton, C. A.
|
|
<strong>Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy.</strong>
|
|
Molec. Cell 10: 35-44, 2002.
|
|
|
|
|
|
[PubMed: 12150905]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s1097-2765(02)00563-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Meyer-Kleine, C., Ricker, K., Otto, M., Koch, M. C.
|
|
<strong>A recurrent 14 bp deletion in the CLCN1 gene associated with generalized myotonia (Becker).</strong>
|
|
Hum. Molec. Genet. 3: 1015-1016, 1994.
|
|
|
|
|
|
[PubMed: 7951215]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/3.6.1015]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Meyer-Kleine, C., Steinmeyer, K., Ricker, K., Jentsch, T. J., Koch, M. C.
|
|
<strong>Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCN1) leading to myotonia.</strong>
|
|
Am. J. Hum. Genet. 57: 1325-1334, 1995.
|
|
|
|
|
|
[PubMed: 8533761]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mindell, J. A., Maduke, M., Miller, C., Grigorieff, N.
|
|
<strong>Projection structure of a CIC-type chloride channel at 6.5-angstrom resolution.</strong>
|
|
Nature 409: 219-223, 2001.
|
|
|
|
|
|
[PubMed: 11196649]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/35051631]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nagamitsu, S., Matsuura, T., Khajavi, M., Armstrong, R., Gooch, C., Harati, Y., Ashizawa, T.
|
|
<strong>A 'dystrophic' variant of autosomal recessive myotonia congenita caused by novel mutations in the CLCN1 gene.</strong>
|
|
Neurology 55: 1697-1703, 2000.
|
|
|
|
|
|
[PubMed: 11113225]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.55.11.1697]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pusch, M., Steinmeyer, K., Koch, M. C., Jentsch, T. J.
|
|
<strong>Mutations in dominant human myotonia congenita drastically alter the voltage dependence of the CIC-1 chloride channel.</strong>
|
|
Neuron 15: 1455-1463, 1995.
|
|
|
|
|
|
[PubMed: 8845168]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0896-6273(95)90023-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pusch, M.
|
|
<strong>Myotonia caused by mutations in the muscle chloride channel gene CLCN1.</strong>
|
|
Hum. Mutat. 19: 423-434, 2002.
|
|
|
|
|
|
[PubMed: 11933197]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.10063]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Raja Rayan, D. L., Haworth, A., Sud, R., Matthews, E., Fialho, D., Burge, J., Portaro, S., Schorge, S., Tuin, K., Lunt, P., McEntagart, M., Toscano, A., Davis, M. B., Hanna, M. G.
|
|
<strong>A new explanation for recessive myotonia congenita: exon deletions and duplications in CLCN1.</strong>
|
|
Neurology 78: 1953-1958, 2012.
|
|
|
|
|
|
[PubMed: 22649220]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/WNL.0b013e318259e19c]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rudel, R.
|
|
<strong>The myotonic mouse--a realistic model for the study of human recessive generalized myotonia.</strong>
|
|
Trends Neurosci. 13: 1-3, 1990.
|
|
|
|
|
|
[PubMed: 1688667]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0166-2236(90)90049-g]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ryan, A., Rudel, R., Kuchenbecker, M., Fahlke, C.
|
|
<strong>A novel alteration of muscle chloride channel gating in myotonia levior.</strong>
|
|
J. Physiol. 545: 345-354, 2002.
|
|
|
|
|
|
[PubMed: 12456816]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1113/jphysiol.2002.027037]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Steinmeyer, K., Klocke, R., Ortland, C., Gronemeier, M., Jockusch, H., Grunder, S., Jentsch, T. J.
|
|
<strong>Inactivation of muscle chloride channel by transposon insertion in myotonic mice.</strong>
|
|
Nature 354: 304-308, 1991.
|
|
|
|
|
|
[PubMed: 1659665]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/354304a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Steinmeyer, K., Lorenz, C., Pusch, M., Koch, M. C., Jentsch, T. J.
|
|
<strong>Multimeric structure of ClC-1 chloride channel revealed by mutations in dominant myotonia congenita (Thomsen).</strong>
|
|
EMBO J. 13: 737-743, 1994.
|
|
|
|
|
|
[PubMed: 8112288]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1994.tb06315.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Suetterlin, K., Matthews, E., Sud, R., McCall, S., Fialho, D., Burge, J., Jayaseelan, D., Haworth, A., Sweeney, M. G., Kullmann, D. M., Schorge, S., Hanna, M. G., Mannikko, R.
|
|
<strong>Translating genetic and functional data into clinical practice: a series of 223 families with myotonia.</strong>
|
|
Brain 145: 607-620, 2022.
|
|
|
|
|
|
[PubMed: 34529042]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/awab344]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sun, C., Tranebjaerg, L., Torbergsen, T., Holmgren, G., Van Ghelue, M.
|
|
<strong>Spectrum of CLCN1 mutations in patients with myotonia congenita in northern Scandinavia.</strong>
|
|
Europ. J. Hum. Genet. 9: 903-909, 2001. Note: Erratum: Europ. J. Hum. Genet. 18: 264 only, 2010.
|
|
|
|
|
|
[PubMed: 11840191]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5200736]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thomasen, E.
|
|
<strong>Myotonia, Thomsen's disease. Paramyotonia, and dystrophia myotonica.</strong>
|
|
Op. Ex Domo Biol. Hered. Hum. U. Hafniensis 17: 11-251, 1948.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thomsen, J.
|
|
<strong>Tonische Kraempfe in willkuerlich beweglichen Muskeln in Folge von ererbter psychischer Disposition: Ataxia muscularis?</strong>
|
|
Arch. Psychiat. Nervenkr. 6: 702-718, 1876.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vindas-Smith, R., Fiore, M., Vasquez, M., Cuenca, P., del Valle, G., Lagostena, L., Gaitan-Penas, H., Estevez, R., Pusch, M., Morales, F.
|
|
<strong>Identification and functional characterization of CLCN1 mutations found in nondystrophic myotonia patients.</strong>
|
|
Hum. Mutat. 37: 74-83, 2016.
|
|
|
|
|
|
[PubMed: 26510092]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.22916]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wollnik, B., Kubisch, C., Steinmeyer, K., Pusch, M.
|
|
<strong>Identification of functionally important regions of the muscular chloride channel CIC-1 by analysis of recessive and dominant myotonic mutations.</strong>
|
|
Hum. Molec. Genet. 6: 805-811, 1997.
|
|
|
|
|
|
[PubMed: 9158157]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/6.5.805]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wu, H., Olson, E. N.
|
|
<strong>Activation of the MEF2 transcription factor in skeletal muscles from myotonic mice.</strong>
|
|
J. Clin. Invest. 109: 1327-1333, 2002.
|
|
|
|
|
|
[PubMed: 12021248]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI15417]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhang, J., Sanguinetti, M. C., Kwiecinski, H., Ptacek, L. J.
|
|
<strong>Mechanism of inverted activation of ClC-1 channels caused by a novel myotonia congenita mutation.</strong>
|
|
J. Biol. Chem. 275: 2999-3005, 2000.
|
|
|
|
|
|
[PubMed: 10644771]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.275.4.2999]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
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Hilary J. Vernon - updated : 05/27/2022<br>Cassandra L. Kniffin - updated : 6/16/2015<br>Cassandra L. Kniffin - updated : 3/11/2013<br>Cassandra L. Kniffin - updated : 10/27/2009<br>Cassandra L. Kniffin - updated : 6/20/2005<br>Patricia A. Hartz - updated : 5/4/2004<br>Victor A. McKusick - updated : 2/6/2003<br>Patricia A. Hartz - updated : 10/8/2002<br>Stylianos E. Antonarakis - updated : 9/10/2002<br>Michael B. Petersen - updated : 8/19/2002<br>Victor A. McKusick - updated : 4/12/2002<br>Ada Hamosh - updated : 1/17/2002<br>Kathryn R. Wagner - updated : 8/6/2001<br>Ada Hamosh - updated : 1/9/2001<br>Ada Hamosh - updated : 2/11/2000<br>Victor A. McKusick - updated : 5/6/1998<br>Victor A. McKusick - updated : 6/23/1997<br>Victor A. McKusick - updated : 5/16/1997<br>Victor A. McKusick - updated : 4/21/1997<br>Orest Hurko - updated : 3/9/1996
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