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Entry
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- *603967 - SODIUM VOLTAGE-GATED CHANNEL, ALPHA SUBUNIT 4; SCN4A
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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">*603967</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/603967">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<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 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=ENSG00000007314;t=ENST00000435607" 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=6329" 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=603967" 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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</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=ENSG00000007314;t=ENST00000435607" 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_000334" 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_000334" 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=603967" 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=04912&isoform_id=04912_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/SCN4A" 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/292487,338213,908809,3080670,13242874,31788956,93587342,119614631,119614632,292495096" 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/P35499" 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=6329" 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=ENSG00000007314;t=ENST00000435607" 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=SCN4A" 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=SCN4A" 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+6329" 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/SCN4A" 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:6329" 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/6329" 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=chr17&hgg_gene=ENST00000435607.3&hgg_start=63938554&hgg_end=63972918&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:10591" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/scn4a" 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=603967[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=603967[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/SCN4A/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000007314" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=SCN4A" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=SCN4A" 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=SCN4A" 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/SCN4A" 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=SCN4A&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/PA35006" 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:10591" 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/FBgn0285944.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:98250" 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/SCN4A#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:98250" 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/6329/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/OMIA000785/" 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=6329" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-051201-1" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=SCN4A&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> 304737009, 41574007, 702355008, 715788001, 715789009<br />
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<strong>ICD10CM:</strong> G71.12, G71.19, G72.3<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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603967
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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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SODIUM VOLTAGE-GATED CHANNEL, ALPHA SUBUNIT 4; SCN4A
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</span>
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</h3>
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</div>
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<div>
|
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
SODIUM CHANNEL, VOLTAGE-GATED, TYPE IV, ALPHA SUBUNIT<br />
|
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NAV1.4
|
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</span>
|
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=SCN4A" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SCN4A</a></em></strong>
|
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</span>
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/17/852?start=-3&limit=10&highlight=852">17q23.3</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr17:63938554-63972918&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'})">17:63,938,554-63,972,918</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
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</div>
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<div>
|
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<br />
|
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</div>
|
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<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
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</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
|
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<th>
|
|
Location
|
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</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=620351,620369,170500,613345,614198,608390,168300" 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="7">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/17/852?start=-3&limit=10&highlight=852">
|
|
17q23.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Congenital myopathy 22A, classic
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/620351"> 620351 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
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</span>
|
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</td>
|
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<td>
|
|
<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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</span>
|
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</td>
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</tr>
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
Congenital myopathy 22B, severe fetal
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/620369"> 620369 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
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</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
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|
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<tr>
|
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<td>
|
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<span class="mim-font">
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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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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<p>The SCN4A gene encodes the alpha subunit of the skeletal muscle voltage-gated sodium channel Na(v)1.4. This channel is essential for the generation and propagation of the muscle action potential needed for muscle contraction (summary by <a href="#69" class="mim-tip-reference" title="Zaharieva, I. T., Thor, M. G., Oates, E. C., van Karnebeek, C., Hendson, G., Blom, E., Witting, N., Rasmussen, M., Gabbett, M. T., Ravenscroft, G., Sframeli, M., Suetterlin, K., and 28 others. <strong>Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy.</strong> Brain 139: 674-691, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26700687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26700687</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26700687[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/awv352" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26700687">Zaharieva et al., 2016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26700687" 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="#66" class="mim-tip-reference" title="Wang, J., Rojas, C. V., Zhou, J., Schwartz, L. S., Nicholas, H., Hoffman, E. P. <strong>Sequence and genomics structure of the human adult skeletal muscle sodium channel alpha subunit gene on 17q.</strong> Biochem. Biophys. Res. Commun. 182: 794-801, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1310396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1310396</a>] [<a href="https://doi.org/10.1016/0006-291x(92)91802-w" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1310396">Wang et al. (1992)</a> deduced the amino acid sequence of the SCN4A gene from adult human skeletal muscle by cross-species PCR-mediated cloning and sequencing of the cDNA. The protein consists of 1,836 residues and shows 93% sequence identity to the alpha subunit from rat adult skeletal muscle and 70% identity to the alpha subunit from other mammalian tissues. Similar results were reported by <a href="#20" class="mim-tip-reference" title="George, A. L., Jr., Komisarof, J., Kallen, R. G., Barchi, R. L. <strong>Primary structure of the adult human skeletal muscle voltage-dependent sodium channel.</strong> Ann. Neurol. 31: 131-137, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1315496/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1315496</a>] [<a href="https://doi.org/10.1002/ana.410310203" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1315496">George et al. (1992)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1315496+1310396" 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="#5" class="mim-tip-reference" title="Bergareche, A., Bednarz, M. Sanchez, E., Krebs, C. E., Ruiz-Martinez, J., De La Riva, P., Makarov, V., Gorostidi, A., Jurkat-Rott, K., Marti-Masso, J. F., Paisan-Ruiz, C. <strong>SCN4A pore mutation pathogenetically contributes to autosomal dominant essential tremor and may increase susceptibility to epilepsy.</strong> Hum. Molec. Genet. 24: 7111-7120, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26427606/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26427606</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26427606[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddv410" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26427606">Bergareche et al. (2015)</a> found expression of the SCN4A gene in mouse skeletal muscle and brain, as well as in human cerebral cortex, suggesting that it has a role in neuronal tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26427606" 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="McClatchey, A. I., Lin, C. S., Wang, J., Hoffman, E. P., Rojas, C., Gusella, J. F. <strong>The genomic structure of the human skeletal muscle sodium channel gene.</strong> Hum. Molec. Genet. 1: 521-527, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1339144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1339144</a>] [<a href="https://doi.org/10.1093/hmg/1.7.521" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1339144">McClatchey et al. (1992)</a> and <a href="#19" class="mim-tip-reference" title="George, A. L., Jr., Iyer, G. S., Kleinfield, R., Kallen, R. G., Barchi, R. L. <strong>Genomic organization of the human skeletal muscle sodium channel gene.</strong> Genomics 15: 598-606, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8385647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8385647</a>] [<a href="https://doi.org/10.1006/geno.1993.1113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8385647">George et al. (1993)</a> determined that the SCN4A gene contains 24 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8385647+1339144" 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="#16" class="mim-tip-reference" title="Fontaine, B., Khurana, T. S., Hoffman, E. P., Bruns, G. A. P., Haines, J. L., Trofatter, J. A., Hanson, M. P., Rich, J., McFarlane, H., Yasek, D. M., Romano, D., Gusella, J. F., Brown, R. H., Jr. <strong>Hyperkalemic periodic paralysis and the adult muscle sodium channel alpha-subunit gene.</strong> Science 250: 1000-1002, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2173143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2173143</a>] [<a href="https://doi.org/10.1126/science.2173143" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2173143">Fontaine et al. (1990)</a> cloned portions of the adult SCN4A gene and localized it to chromosome 17 using somatic cell hybrids. One of the probes used in this study showed hybridization also to chromosome 3, probably indicating cross-hybridization with the fetal gene. Using RFLPs, they found that the SCN4A gene was closely linked to the growth hormone gene (GH1; <a href="/entry/139250">139250</a>) on 17q (maximum lod = 9.89 at theta = 0.00). Furthermore, with very high odds, the gene was placed between NGFR (<a href="/entry/162010">162010</a>) and TK1 (<a href="/entry/188300">188300</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2173143" 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 clones of the SCN4A gene, <a href="#21" class="mim-tip-reference" title="George, A. L., Jr., Ledbetter, D. H., Kallen, R. G., Barchi, R. L. <strong>Assignment of a human skeletal muscle sodium channel alpha-subunit gene (SCN4A) to 17q23.1-25.3.</strong> Genomics 9: 555-556, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1851726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1851726</a>] [<a href="https://doi.org/10.1016/0888-7543(91)90425-e" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1851726">George et al. (1991)</a> found a regional assignment of 17q23.1-q25.3 by study of somatic cell hybrids that retained various portions of human chromosome 17. The growth hormone gene cluster (<a href="/entry/139250">139250</a>), which spans 47 kb, was assigned to 17q22-q24. <a href="#4" class="mim-tip-reference" title="Bennani-Baiti, I. M., Jones, B. K., Liebhaber, S. A., Cooke, N. E. <strong>Physical linkage of the human growth hormone gene cluster and the skeletal muscle sodium channel alpha-subunit gene (SCN4A) on chromosome 17.</strong> Genomics 29: 647-652, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8575757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8575757</a>] [<a href="https://doi.org/10.1006/geno.1995.9954" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8575757">Bennani-Baiti et al. (1995)</a> demonstrated that the GH gene cluster and the SCN4A gene colocalized to a single 525-kb YAC. Furthermore, restriction mapping and sequencing demonstrated that the SCN4A gene and the entire GH gene cluster are contained within 100 kb on chromosome 17 and are separated by only 21.5 kb. Remarkably, <a href="#4" class="mim-tip-reference" title="Bennani-Baiti, I. M., Jones, B. K., Liebhaber, S. A., Cooke, N. E. <strong>Physical linkage of the human growth hormone gene cluster and the skeletal muscle sodium channel alpha-subunit gene (SCN4A) on chromosome 17.</strong> Genomics 29: 647-652, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8575757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8575757</a>] [<a href="https://doi.org/10.1006/geno.1995.9954" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8575757">Bennani-Baiti et al. (1995)</a> found that multiple elements critical to tissue-specific transcriptional activation of the GH gene lie within the SCN4A gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1851726+8575757" 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>Heterozygous missense mutations in the SCN4A gene have been identified in a group of related muscular disorders, including hyperkalemic periodic paralysis (HYPP; <a href="/entry/170500">170500</a>), paramyotonia congenita (PMC; <a href="/entry/168300">168300</a>), a group of disorders classified as potassium-aggravated myotonia (<a href="/entry/608390">608390</a>), and hypokalemic periodic paralysis type 2 (HOKPP2; <a href="/entry/613345">613345</a>). These mutations result in a gain-of-function effect via different mechanisms. Less commonly, biallelic loss-of-function or hypomorphic mutations in the SCN4A gene cause congenital myasthenic syndrome-16 (CMS16; <a href="/entry/614198">614198</a>), classic congenital myopathy-22A (CMYO22A; <a href="/entry/620351">620351</a>), and severe fetal congenital myopathy-22B (CMYO22B; <a href="/entry/620369">620369</a>). The severity of the disorder seems to correlate with the detrimental effect of the mutation on SCN4A function (<a href="#9" class="mim-tip-reference" title="Cannon, S. C. <strong>When all is lost...a severe myopathy with hypotonia from sodium channel mutations.</strong> Brain 139: 642-644, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26917582/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26917582</a>] [<a href="https://doi.org/10.1093/brain/awv400" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26917582">Cannon, 2016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26917582" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Ackerman, M. J., Clapham, D. E. <strong>Ion channels--basic science and clinical disease.</strong> New Eng. J. Med. 336: 1575-1586, 1997. Note: Erratum: New Eng. J. Med. 337: 579 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9164815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9164815</a>] [<a href="https://doi.org/10.1056/NEJM199705293362207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9164815">Ackerman and Clapham (1997)</a> gave a comprehensive review of the role of ion channel defects in disease and provided figures illustrating the physiology and structure of ion channels and patch-clamp measurement of ion channel activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9164815" 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>Hyperkalemic Periodic Paralysis</em></strong></p><p>
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In 3 of 7 unrelated patients with HYPP (<a href="/entry/170500">170500</a>), <a href="#46" class="mim-tip-reference" title="Ptacek, L. J., George, A. L., Jr., Griggs, R. C., Tawil, R., Kallen, R. G., Barchi, R. L., Robertson, M., Leppert, M. F. <strong>Identification of a mutation in the gene causing hyperkalemic periodic paralysis.</strong> Cell 67: 1021-1027, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1659948/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1659948</a>] [<a href="https://doi.org/10.1016/0092-8674(91)90374-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1659948">Ptacek et al. (1991)</a> identified the same mutation in the SCN4A gene (T704M; <a href="#0001">603967.0001</a>). In 9 of 12 families with HYPP, <a href="#15" class="mim-tip-reference" title="Feero, W. G., Wang, J., Barany, F., Zhou, J., Todorovic, S. M., Conwit, R., Galloway, G., Hausmanowa-Petrusewicz, I., Fidzianska, A., Arahata, K., Wessel, H. B., Wadelius, C., Marks, H. G., Hartlage, P., Hayakawa, H., Hoffman, E. P. <strong>Hyperkalemic periodic paralysis: rapid molecular diagnosis and relationship of genotype to phenotype in 12 families.</strong> Neurology 43: 668-673, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8385748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8385748</a>] [<a href="https://doi.org/10.1212/wnl.43.4.668" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8385748">Feero et al. (1993)</a> identified mutations in the SCN4A gene: 3 families had the M1592V mutation (<a href="#0002">603967.0002</a>) and 6 had the T704M mutation. No mutation was identified in 3 families, 1 of whom did not show linkage to the SCN4A gene, suggesting genetic heterogeneity. <a href="#28" class="mim-tip-reference" title="Jurkat-Rott, K., Mitrovic, N., Hang, C., Kouzmekine, A., Iaizzo, P., Herzog, J., Lerche, H., Nicole, S., Vale-Santos, J., Chauveau, D., Fontaine, B., Lehmann-Horn, F. <strong>Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current.</strong> Proc. Nat. Acad. Sci. 97: 9549-9554, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10944223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10944223</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10944223[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.97.17.9549" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10944223">Jurkat-Rott et al. (2000)</a> stated that 5 mutations in the SCN4A gene had been reported in HYPP patients, none of which was directly located in the voltage sensors. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1659948+10944223+8385748" 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>Paramyotonia Congenita</em></strong></p><p>
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In patients with paramyotonia congenita (<a href="/entry/163800">163800</a>), <a href="#39" class="mim-tip-reference" title="McClatchey, A. I., McKenna-Yasek, D., Cros, D., Worthen, H. G., Kuncl, R. W., DeSilva, S. M., Cornblath, D. R., Gusella, J. F., Brown, R. H., Jr. <strong>Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel.</strong> Nature Genet. 2: 148-152, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1338909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1338909</a>] [<a href="https://doi.org/10.1038/ng1092-148" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1338909">McClatchey et al. (1992)</a> identified 2 point mutations in the III-IV cytoplasmic loop region of the SCN4A gene (<a href="#0007">603967.0007</a>-<a href="#0008">603967.0008</a>), and suggested that these are the first known examples of molecular definition of temperature-sensitive mutations. The authors postulated that the mutations restrict the channel movement in response to transmembrane potential, and that even a minor drop in temperature may impede movement of the loop enough to allow an abnormal sodium flux. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1338909" 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="Gay, S., Dupuis, D., Faivre, L., Masurel-Paulet, A., Labenne, M., Colombani, M., Soichot, P., Huet, F., Hainque, B., Sternberg, D., Fontaine, B., Gouyon, J.-B., Thauvin-Robinet, C. <strong>Severe neonatal non-dystrophic myotonia secondary to a novel mutation of the voltage-gated sodium channel (SCN4A) gene.</strong> Am. J. Med. Genet. 146A: 380-383, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18203179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18203179</a>] [<a href="https://doi.org/10.1002/ajmg.a.32141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18203179">Gay et al. (2008)</a> reported a female infant with severe fatal neonatal nondystrophic myotonia in whom they identified a heterozygous mutation (N1297K; <a href="#0027">603967.0027</a>) in the SCN4A gene. The phenotype showed overlapping features of paramyotonia congenita and hyperkalemic periodic paralysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18203179" 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>Myotonia, Potassium-Aggravated</em></strong></p><p>
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<a href="#34" class="mim-tip-reference" title="Lerche, H., Heine, R., Pika, U., George, A. L., Jr., Mitrovic, N., Browatzki, M., Weiss, T., Rivet-Bastide, M., Franke, C., Lomonaco, M., Ricker, K., Lehmann-Horn, F. <strong>Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III-IV linker.</strong> J. Physiol. 470: 13-22, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8308722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8308722</a>] [<a href="https://doi.org/10.1113/jphysiol.1993.sp019843" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8308722">Lerche et al. (1993)</a> identified heterozygous mutations in the same codon of the SCN4A gene (G1306V, <a href="#0007">603967.0007</a>; G1306A, <a href="#0012">603967.0012</a>; and G1306E, <a href="#0025">603967.0025</a>) in patients with exercise and potassium-aggravated myotonia, myotonia fluctuans, and myotonia permanens, respectively (see <a href="/entry/608390">608390</a>). Patch-clamp recordings on patient muscle samples showed slower sodium fast channel inactivation and an increase in late channel opening, resulting in a steady-state inward current, sustained muscle depolarization, and muscle fiber hyperexcitability. The findings indicated that SCN4A residue 1306 is important for sodium channel inactivation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8308722" 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 with dominantly inherited potassium-aggravated myotonia (<a href="/entry/608390">608390</a>), <a href="#43" class="mim-tip-reference" title="Orrell, R. W., Jurkat-Rott, K., Lehmann-Horn, F., Lane, R. J. M. <strong>Familial cramp due to potassium-aggravated myotonia.</strong> J. Neurol. Neurosurg. Psychiat. 65: 569-572, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9771789/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9771789</a>] [<a href="https://doi.org/10.1136/jnnp.65.4.569" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9771789">Orrell et al. (1998)</a> found a heterozygous mutation in the SCN4A gene (<a href="#0009">603967.0009</a>). The myotonic phenotype was characterized by painful cramps, stiffness without weakness, fluctuation of symptoms, and cold sensitivity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9771789" 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>Hypokalemic Periodic Paralysis</em></strong></p><p>
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In 4 affected individuals of family with hypokalemic periodic paralysis, <a href="#8" class="mim-tip-reference" title="Bulman, D. E., Scoggan, K. A., van Oene, M. D., Nicolle, M. W., Hahn, A. F., Tollar, L. L., Ebers, G. C. <strong>A novel sodium channel mutation in a family with hypokalemic periodic paralysis.</strong> Neurology 53: 1932-1936, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10599760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10599760</a>] [<a href="https://doi.org/10.1212/wnl.53.9.1932" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10599760">Bulman et al. (1999)</a> identified a heterozygous missense mutation in the SCN4A gene (<a href="#0015">603967.0015</a>). In several families with HOKPP in which defects of the CACNL1A3 gene (CACNA1S; <a href="/entry/114208">114208</a>) had been excluded, <a href="#28" class="mim-tip-reference" title="Jurkat-Rott, K., Mitrovic, N., Hang, C., Kouzmekine, A., Iaizzo, P., Herzog, J., Lerche, H., Nicole, S., Vale-Santos, J., Chauveau, D., Fontaine, B., Lehmann-Horn, F. <strong>Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current.</strong> Proc. Nat. Acad. Sci. 97: 9549-9554, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10944223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10944223</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10944223[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.97.17.9549" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10944223">Jurkat-Rott et al. (2000)</a> identified 2 heterozygous disease-causing missense mutations in the SCN4A gene (<a href="#0016">603967.0016</a>-<a href="#0017">603967.0017</a>). This form of HOKPP did not differ clinically from the form of the disorder due to mutations in the gene for CACNL1A3. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10599760+10944223" 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="#58" class="mim-tip-reference" title="Sokolov, S., Scheuer, T., Catterall, W. A. <strong>Gating pore current in an inherited ion channelopathy.</strong> Nature 446: 76-78, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17330043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17330043</a>] [<a href="https://doi.org/10.1038/nature05598" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17330043">Sokolov et al. (2007)</a> showed that, in contrast with the well-established paradigm in which alterations in control of ion conductance through the central pore of ion channels impair cell function, 3 mutations in gating charge-carrying arginine residues in an S4 segment that cause hypokalemic periodic paralysis (HOKPP) induce a hyperpolarization-activated cationic leak through the voltage sensor of the skeletal muscle Nav1.4 channel. This gating pore current is active at the resting membrane potential and closed by depolarizations that activate the voltage sensor. It has similar permeability to sodium, potassium, and cesium ions, but the organic monovalent cations tetraethylammonium and N-methyl-D-glucamine are much less permeant. The inorganic divalent cations barium, calcium, and zinc are not detectably permeant and block the gating pore at millimolar concentrations. <a href="#58" class="mim-tip-reference" title="Sokolov, S., Scheuer, T., Catterall, W. A. <strong>Gating pore current in an inherited ion channelopathy.</strong> Nature 446: 76-78, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17330043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17330043</a>] [<a href="https://doi.org/10.1038/nature05598" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17330043">Sokolov et al. (2007)</a> concluded that their results revealed gating pore current in naturally occurring disease mutations of an ion channel and showed a clear correlation between mutations that cause gating pore current and hypokalemic periodic paralysis. This gain-of-function gating pore current would contribute in an important way to the dominantly inherited membrane depolarization, action potential failure, flaccid paralysis, and cytopathology that are characteristic of hypokalemic periodic paralysis. <a href="#58" class="mim-tip-reference" title="Sokolov, S., Scheuer, T., Catterall, W. A. <strong>Gating pore current in an inherited ion channelopathy.</strong> Nature 446: 76-78, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17330043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17330043</a>] [<a href="https://doi.org/10.1038/nature05598" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17330043">Sokolov et al. (2007)</a> postulated that their observations might be generalizable to other ion channelopathies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17330043" 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="#36" class="mim-tip-reference" title="Matthews, E., Labrum, R., Sweeney, M. G., Sud, R., Haworth, A., Chinnery, P. F., Meola, G., Schorge, S., Kullmann, D. M., Davis, M. B., Hanna, M. G. <strong>Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis.</strong> Neurology 72: 1544-1547, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19118277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19118277</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19118277[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/10.1212/01.wnl.0000342387.65477.46" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19118277">Matthews et al. (2009)</a> identified mutations in the CACNA1S (<a href="/entry/114208">114208</a>) or SCN4A gene in 74 (almost 90%) of 83 patients with HOKPP. All of the mutations, including 3 novel mutations, affected arginine residues in the S4 voltage sensing region in 1 of the transmembrane domains of each gene. The most common CACNA1S mutations affected residues arg528 (25 cases) and arg1239 (39 cases) (see, e.g., R1239H; <a href="/entry/114208#0001">114208.0001</a> and R528H; <a href="/entry/114208#0003">114208.0003</a>). The most common SCN4A mutations affected residues arg672 (see, e.g., <a href="#0016">603967.0016</a>) and arg1132. The findings supported the hypothesis that loss of positive charge in S4 voltage sensors is important to the pathogenesis of this disorder. (<a href="#58" class="mim-tip-reference" title="Sokolov, S., Scheuer, T., Catterall, W. A. <strong>Gating pore current in an inherited ion channelopathy.</strong> Nature 446: 76-78, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17330043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17330043</a>] [<a href="https://doi.org/10.1038/nature05598" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17330043">Sokolov et al., 2007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19118277+17330043" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Francis, D. G., Rybalchenko, V., Struyk, A., Cannon, S. C. <strong>Leaky sodium channels from voltage sensor mutations in periodic paralysis, but not paramyotonia.</strong> Neurology 76: 1635-1641, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21490317/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21490317</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21490317[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.0b013e318219fb57" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21490317">Francis et al. (2011)</a> demonstrated that an R1132Q mutation (<a href="#0030">603967.0030</a>) in the domain III voltage sensor domain of SCN4A found in a family with HOKPP created an anomalous gating pore current similar to that observed by <a href="#58" class="mim-tip-reference" title="Sokolov, S., Scheuer, T., Catterall, W. A. <strong>Gating pore current in an inherited ion channelopathy.</strong> Nature 446: 76-78, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17330043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17330043</a>] [<a href="https://doi.org/10.1038/nature05598" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17330043">Sokolov et al. (2007)</a>. This current is sufficient to depolarize and render the muscle fiber inexcitable particularly during low external potassium. The findings suggested a mechanism for loss of sarcolemmal excitability during attacks of weakness in HOKPP. In contrast, the R1148C mutation (<a href="#0003">603967.0003</a>) causing PMC does not result in gating pore abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21490317+17330043" 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>Congenital Myasthenic Syndrome 16</em></strong></p><p>
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In a patient with congenital myasthenic syndrome-16 (CMS16; <a href="/entry/614198">614198</a>) associated with fatigable generalized weakness and recurrent attacks of respiratory and bulbar paralysis since birth, <a href="#62" class="mim-tip-reference" title="Tsujino, A., Maertens, C., Ohno, K., Shen, X.-M., Fukuda, T., Harper, C. M., Cannon, S. C., Engel, A. G. <strong>Myasthenic syndrome caused by mutation of the SCN4A sodium channel.</strong> Proc. Nat. Acad. Sci. 100: 7377-7382, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12766226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12766226</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12766226[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.1230273100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12766226">Tsujino et al. (2003)</a> identified compound heterozygous variants in the SCN4A gene (V1442E, <a href="#0018">603967.0018</a> and S246L, <a href="#0031">603967.0031</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12766226" 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 57-year-old woman, born of consanguineous parents, with CMS16, <a href="#2" class="mim-tip-reference" title="Arnold, W. D., Feldman, D. H., Ramirez, S., He, L., Kassar, D., Quick, A., Klassen, T. L., Lara, M., Nguyen, J., Kissel, J. T., Lossin, C., Maselli, R. A. <strong>Defective fast inactivation recovery of Na(v)1.4 in congenital myasthenic syndrome.</strong> Ann. Neurol. 77: 840-850, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25707578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25707578</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25707578[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/10.1002/ana.24389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25707578">Arnold et al. (2015)</a> identified a homozygous missense mutation in the SCN4A gene (R1457H; <a href="#0032">603967.0032</a>). In vitro electrophysiologic studies showed that the mutation caused a 25-mV hyperpolarizing shift in the voltage dependence of inactivation, resulting in enhanced fast inactivation as well as slowed recovery from fast inactivation. In addition, repetitive stimuli elicited markedly weaker current responses. These changes resulted in reduced channel availability, which could explain the patient's muscle weakness. The unaffected parents and sibs were heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25707578" 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 26-year-old Lebanese woman, born of consanguineous parents, with CMS16 and features of normokalemic periodic paralysis, <a href="#23" class="mim-tip-reference" title="Habbout, K., Poulin, H., Rivier, F., Giuliano, S., Sternberg, D., Fontaine, B., Eymard, B., Morales, R. J., Echenne, B., King, L., Hanna, M. G., Mannikko, R., Chahine, M., Nicole, S., Bendahhou, S. <strong>A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with periodic paralysis.</strong> Neurology 86: 161-169, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26659129/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26659129</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26659129[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.0000000000002264" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26659129">Habbout et al. (2016)</a> identified a homozygous missense mutation in the SCN4A gene (R1454W; <a href="#0041">603967.0041</a>). Each unaffected parent was heterozygous for the mutation. In vitro functional expression studies showed that the mutation resulted in a loss-of-function effect, with slowed current decay, slowed fast inactivation, and increased activation time compared to wildtype. Slowed inactivation was also disturbed. Current density was not affected, but there was a decrease in current amplitude in response to repetitive stimulation above 10 Hz. The findings thus showed a combination of gating behaviors that favor the inactivation state; defective inactivation may induce fatigable weakness during muscle firing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26659129" 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>Congenital Myopathy 22A, Classic</em></strong></p><p>
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In 8 patients from 4 unrelated families (families 1-4) with classic congenital myopathy-22A (CMYO22A; <a href="/entry/620351">620351</a>), <a href="#69" class="mim-tip-reference" title="Zaharieva, I. T., Thor, M. G., Oates, E. C., van Karnebeek, C., Hendson, G., Blom, E., Witting, N., Rasmussen, M., Gabbett, M. T., Ravenscroft, G., Sframeli, M., Suetterlin, K., and 28 others. <strong>Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy.</strong> Brain 139: 674-691, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26700687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26700687</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26700687[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/awv352" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26700687">Zaharieva et al. (2016)</a> identified homozygous or compound heterozygous mutations in the SCN4A gene (see, e.g., <a href="#0034">603967.0034</a>-<a href="#0035">603967.0035</a>). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in all families. There were missense, nonsense, frameshift, and splice site mutations distributed throughout the gene. Electrophysiologic studies of the missense variants in HEK293 cells showed that they caused a loss-of-function effect of varying degrees. All patients carried 1 mutation that resulted in a completely nonfunctional channel in combination with a hypomorphic allele. None of the carrier parents was affected, indicating that loss of function in only 1 SCN4A allele is insufficient to cause a clinical phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26700687" 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 2 brothers, born of unrelated parents of East Indian descent, with CMYO22A, <a href="#22" class="mim-tip-reference" title="Gonorazky, H. D., Marshall, C. R., Al-Murshed, M., Hazrati, L. N., Thor, M. G., Hanna, M. G., Mannikko, R., Ray, P. N., Yoon, G. <strong>Congenital myopathy with "corona" fibres, selective muscle atrophy, and craniosynostosis associated with novel recessive mutations in SCN4A.</strong> Neuromusc. Disord. 27: 574-580, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28262468/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28262468</a>] [<a href="https://doi.org/10.1016/j.nmd.2017.02.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28262468">Gonorazky et al. (2017)</a> identified compound heterozygous missense mutations in the SCN4A gene (C375R, <a href="#0039">603967.0039</a> and R1142Q, <a href="#0040">603967.0040</a>). The mutations, which were found by exome sequencing, segregated with the disorder in the family. In vitro electrophysiologic studies in HEK293 cells showed that the C375R mutation abolished sodium activity and caused a complete loss of SCN4A function, whereas the R1142Q mutation was hypomorphic with reduced peak current densities due to a 4-mV depolarizing shift of activation. Fast inactivation properties of the R1142Q mutant channel were also mildly affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28262468" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In an 18-year-old girl, born of unrelated parents, with CMYO22A, <a href="#6" class="mim-tip-reference" title="Berghold, V. M., Koko, M., Berutti, R., Plecko, B. <strong>Novel SCN4A variant associated with a severe congenital myasthenic syndrome/myopathy phenotype.</strong> Front. Pediat. 10: 944784, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36090556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36090556</a>] [<a href="https://doi.org/10.3389/fped.2022.944784" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36090556">Berghold et al. (2022)</a> identified compound heterozygous missense mutations in the SCN4A gene (R1454W, <a href="#0041">603967.0041</a> and N1205K, <a href="#0042">603967.0042</a>). The mutations, which were found by whole-exome sequencing, were inherited from the unaffected parents. R1454W, located in the voltage sensor of domain IV, had been demonstrated to be a loss-of-function variant by <a href="#23" class="mim-tip-reference" title="Habbout, K., Poulin, H., Rivier, F., Giuliano, S., Sternberg, D., Fontaine, B., Eymard, B., Morales, R. J., Echenne, B., King, L., Hanna, M. G., Mannikko, R., Chahine, M., Nicole, S., Bendahhou, S. <strong>A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with periodic paralysis.</strong> Neurology 86: 161-169, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26659129/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26659129</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26659129[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.0000000000002264" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26659129">Habbout et al. (2016)</a>. The N1205K, located in a region forming the channel pore, was a novel variant. Functional studies of N1205K were not performed, but it was predicted to cause a loss of function based on studies of paralogous variants in other SCNA genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=26659129+36090556" 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>Congenital Myopathy 22B, Severe Fetal</em></strong></p><p>
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In 6 patients from 2 unrelated families (families 5 and 6) with severe fetal congenital myopathy-22B (CMYO22B; <a href="/entry/620369">620369</a>) resulting in death in utero or in the perinatal period, <a href="#69" class="mim-tip-reference" title="Zaharieva, I. T., Thor, M. G., Oates, E. C., van Karnebeek, C., Hendson, G., Blom, E., Witting, N., Rasmussen, M., Gabbett, M. T., Ravenscroft, G., Sframeli, M., Suetterlin, K., and 28 others. <strong>Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy.</strong> Brain 139: 674-691, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26700687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26700687</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26700687[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/awv352" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26700687">Zaharieva et al. (2016)</a> identified homozygous or compound heterozygous mutations in the SCN4A gene. Three sibs in family 5 carried a homozygous missense mutation (P382T; <a href="#0036">603967.0036</a>) that was demonstrated to result in a complete loss of function with no detectable sodium current when expressed in HEK293 cells. Three sibs in family 6 were compound heterozygous for a missense mutation (M203K; <a href="#0037">603967.0037</a>) that was demonstrated to have a hypomorphic effect on channel function, and a nonsense mutation (Y1593X; <a href="#0038">603967.0038</a>) that was predicted to result in a complete loss of channel function. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in all families. None of the carrier parents was affected, indicating that loss of function in only 1 SCN4A allele is insufficient to cause a clinical phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26700687" 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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For discussion of a possible association between essential tremor (see, e.g., ETM1, <a href="/entry/190300">190300</a>) and variation in the SCN4A gene, see <a href="#0033">603967.0033</a>.</p>
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<p>Rudolph et al. (<a href="#54" class="mim-tip-reference" title="Rudolph, J. A., Spier, S. J., Byrns, G., Hoffman, E. P. <strong>Linkage of hyperkalaemic periodic paralysis in Quarter horses to the horse adult skeletal muscle sodium channel gene.</strong> Anim. Genet. 23: 241-250, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1323940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1323940</a>] [<a href="https://doi.org/10.1111/j.1365-2052.1992.tb00136.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1323940">1992</a>, <a href="#55" class="mim-tip-reference" title="Rudolph, J. A., Spier, S. J., Byrns, G., Rojas, C. V., Bernoco, D., Hoffman, E. P. <strong>Periodic paralysis in Quarter horses: a sodium channel mutation disseminated by selective breeding.</strong> Nature Genet. 2: 144-147, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1338908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1338908</a>] [<a href="https://doi.org/10.1038/ng1092-144" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1338908">1992</a>) identified a mutation in the SCN4A gene in Quarter horses with HYPP (see <a href="/entry/170500">170500</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1323940+1338908" 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="#24" class="mim-tip-reference" title="Hayward, L. J., Kim, J. S., Lee, M.-Y., Zhou, H., Kim, J. W., Misra, K., Salajegheh, M., Wu, F., Matsuda, C., Reid, V., Cros, D., Hoffman, E. P., Renaud, J.-M., Cannon, S. C., Brown, R. H., Jr. <strong>Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and potassium-sensitive weakness.</strong> J. Clin. Invest. 118: 1437-1449, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18317596/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18317596</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18317596[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/JCI32638" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18317596">Hayward et al. (2008)</a> introduced a missense substitution corresponding to the human M1592V mutation into the mouse Scn4a gene and found that few homozygous mutant (m/m) mice survived and those that did showed fixed limb weakness, muscle atrophy, and abnormal muscle morphology. Heterozygous (+/m) mice showed only a mild myopathy at 4 months of age, but myopathic changes developed with age and included electrical myotonia, fiber type switching to a more oxidative type, size variation, and internalized nuclei, and +/m muscle developed less tetanic force and exhibited slower relaxation compared with muscle from wildtype controls. Rapid and sustained weakness of isolated mutant muscle was induced when the extracellular K+ concentration was increased to that observed in exercising human muscle interstitium, and weakness was exacerbated by lowering extracellular Ca(2+) and by partial inhibition of the Na+/K+ pump. Mutant muscle recovered from stimulation-induced fatigue more slowly than did control muscle, particularly in the presence of high extracellular K+. <a href="#24" class="mim-tip-reference" title="Hayward, L. J., Kim, J. S., Lee, M.-Y., Zhou, H., Kim, J. W., Misra, K., Salajegheh, M., Wu, F., Matsuda, C., Reid, V., Cros, D., Hoffman, E. P., Renaud, J.-M., Cannon, S. C., Brown, R. H., Jr. <strong>Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and potassium-sensitive weakness.</strong> J. Clin. Invest. 118: 1437-1449, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18317596/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18317596</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18317596[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/JCI32638" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18317596">Hayward et al. (2008)</a> concluded that this myotonia is consistent with persistent Na+ influx through the noninactivating mutant Na+ channel that mildly depolarizes the membrane and thereby increases excitability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18317596" 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="#67" class="mim-tip-reference" title="Wu, F., Mi, W., Fu, Y., Struyk, A., Cannon, S. C. <strong>Mice with an NaV1.4 sodium channel null allele have latent myasthenia, without susceptibility to periodic paralysis.</strong> Brain 139: 1688-1699, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27048647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27048647</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27048647[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/aww070" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27048647">Wu et al. (2016)</a> found that mice homozygous for a null Scn4a allele (exon 12 deletion) did not survive beyond postnatal day 2. Heterozygous mutant mice showed no gross motor deficits. Electrophysiologic studies in heterozygous mice showed that the sodium current amplitude was decreased about 2-fold and subtle myasthenic features were observed on repetitive stimulation at high frequencies. The myasthenic features were termed 'pseudo-myasthenic' because the defect resided in the intrinsic excitability of the muscle fiber rather than at the postsynaptic endplate potential. Heterozygosity for the loss-of-function allele was not sufficient to cause hypokalemic periodic paralysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27048647" 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">rs80338957 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338957;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=rs80338957" 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=rs80338957" 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=RCV000006254 OR RCV000006255 OR RCV000255373 OR RCV000763020 OR RCV002291266 OR RCV003231090 OR RCV004532296" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006254, RCV000006255, RCV000255373, RCV000763020, RCV002291266, RCV003231090, RCV004532296" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006254...</a>
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<p>In 3 of 7 unrelated patients with hyperkalemic periodic paralysis (HYPP; <a href="/entry/170500">170500</a>), <a href="#46" class="mim-tip-reference" title="Ptacek, L. J., George, A. L., Jr., Griggs, R. C., Tawil, R., Kallen, R. G., Barchi, R. L., Robertson, M., Leppert, M. F. <strong>Identification of a mutation in the gene causing hyperkalemic periodic paralysis.</strong> Cell 67: 1021-1027, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1659948/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1659948</a>] [<a href="https://doi.org/10.1016/0092-8674(91)90374-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1659948">Ptacek et al. (1991)</a> identified a heterozygous C-to-T change at a CpG dimer in the SCN4A gene, resulting in a thr704-to-met (T704M) substitution in S5 of domain II in the membrane-spanning segment of the sodium channel protein. All 3 patients had prominent fixed muscle weakness, whereas the remaining 4 did not. In 2 of the families, the mutation cosegregated with HYPP; in the third it appeared to be a de novo mutation. The authors noted that threonine-704 is absolutely conserved in sodium channel genes across highly divergent species. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1659948" 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="#57" class="mim-tip-reference" title="Sillen, A., Wadelius, C., Sundvall, M., Ahlsten, G., Gustavson, K. H. <strong>Hyperkalemic periodic paralysis caused by recurring mutation in the adult muscle sodium channel alpha-subunit gene.</strong> Genet. Counsel. 7: 267-275, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8985730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8985730</a>]" pmid="8985730">Sillen et al. (1996)</a> found the T704M mutation in 2 Swedish families with HYPP. The mutation was linked to different microsatellite alleles, suggesting that the mutation may have arisen independently in the 2 families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8985730" 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 with features of both HYPP and paramyotonia congenita (PMC; <a href="/entry/168300">168300</a>), which the authors termed 'paralysis periodica paramyotonica,' <a href="#30" class="mim-tip-reference" title="Kim, J., Hahn, Y., Sohn, E. H., Lee, Y. J., Yun, J. H., Kim, J. M., Chung, J. H. <strong>Phenotypic variation of a thr704met mutation in skeletal sodium channel gene in a family with paralysis periodica paramyotonica.</strong> J. Neurol. Neurosurg. Psychiat. 70: 618-623, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11309455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11309455</a>] [<a href="https://doi.org/10.1136/jnnp.70.5.618" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11309455">Kim et al. (2001)</a> identified the T704M mutation. Both exercise sensitivity and temperature sensitivity were present, and the authors commented on the phenotypic variation resulting from this mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11309455" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In an Italian kindred in which 9 members were affected with a severe form of HYPP/PMC, <a href="#7" class="mim-tip-reference" title="Brancati, F., Valente, E. M., Davies, N. P., Sarkozy, A., Sweeney, M. G., LoMonaco, M., Pizzuti, A., Hanna, M. G., Dallapiccola, B. <strong>Severe infantile hyperkalaemic periodic paralysis and paramyotonia congenita: broadening the clinical spectrum associated with the T704M mutation in SCN4A.</strong> J. Neurol. Neurosurg. Psychiat. 74: 1339-1341, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12933953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12933953</a>] [<a href="https://doi.org/10.1136/jnnp.74.9.1339" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12933953">Brancati et al. (2003)</a> found the T704M mutation. Onset of the disorder was in the first months of life in all affected patients and the episodes of paralysis increased in severity and frequency, sometimes up to several times a day, with age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12933953" 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="#42" class="mim-tip-reference" title="Miller, T. M., Dias da Silva, M. R., Miller, H. A., Kwiecinski, H., Mendell, J. R., Tawil, R., McManis, P., Griggs, R. C., Angelini, C., Servidei, S., Petajan, J., Dalakas, M. C., Ranum, L. P. W., Fu, Y. H., Ptacek, L. J. <strong>Correlating phenotype and genotype in the periodic paralyses.</strong> Neurology 63: 1647-1655, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15534250/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15534250</a>] [<a href="https://doi.org/10.1212/01.wnl.0000143383.91137.00" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15534250">Miller et al. (2004)</a> identified the T704M mutation in affected members of 10 kindreds with HYPP. All patients had onset before 1 year of age and overall showed only a 50% chance of favorable response to acetazolamide. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15534250" 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="#26" class="mim-tip-reference" title="Hisama, F. M. <strong>Familial periodic paralysis and Charcot-Marie-Tooth disease in a 7-generation family.</strong> Arch. Neurol. 62: 135-138, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15642860/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15642860</a>] [<a href="https://doi.org/10.1001/archneur.62.1.135" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15642860">Hisama (2005)</a> described a 7-generation family in which multiple members were affected with a complicated neurologic phenotype including variable features of neuropathy, myotonia, and periodic paralysis. The same family had been described in the medical literature since 1934. The proband had late-onset demyelinating Charcot-Marie-Tooth disease (CMT1B; <a href="/entry/118200">118200</a>), muscle cramping, and myotonia. His sister had HYPP, and his father had severe childhood-onset CMT and periodic paralysis. Multiple other relatives had similar features of 1 or both disorders. Molecular analysis identified a missense mutation in the MPZ gene (<a href="/entry/159440">159440</a>) in the proband and the SCN4A T704M mutation in the sister; the father was deceased. One other family member tested had the MPZ mutation, and 4 other family members had the SCN4A mutation. <a href="#26" class="mim-tip-reference" title="Hisama, F. M. <strong>Familial periodic paralysis and Charcot-Marie-Tooth disease in a 7-generation family.</strong> Arch. Neurol. 62: 135-138, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15642860/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15642860</a>] [<a href="https://doi.org/10.1001/archneur.62.1.135" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15642860">Hisama (2005)</a> commented on the unusual occurrence of 2 genetically unlinked neurologic disorders in this family and emphasized the diagnostic difficulties. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15642860" 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">rs80338962 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338962;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=rs80338962" 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=rs80338962" 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=RCV000006256 OR RCV000006257 OR RCV000516497 OR RCV000763018 OR RCV005016245" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006256, RCV000006257, RCV000516497, RCV000763018, RCV005016245" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006256...</a>
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<p>In a patient with familial hyperkalemic periodic paralysis (HYPP; <a href="/entry/170500">170500</a>), <a href="#50" class="mim-tip-reference" title="Rojas, C. V., Wang, J., Schwartz, L. S., Hoffman, E. P., Powell, B. R., Brown, R. H., Jr. <strong>A met-to-val mutation in the skeletal muscle Na+ channel alpha-subunit in hyperkalaemic periodic paralysis.</strong> Nature 354: 387-389, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1659668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1659668</a>] [<a href="https://doi.org/10.1038/354387a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1659668">Rojas et al. (1991)</a> identified a heterozygous A-to-G transition in the SCN4A gene, resulting in a met-to-val substitution in a highly conserved region of the alpha subunit, predicted to be in S6 of transmembrane domain IV. The same change was found as a new mutation in a sporadic case. <a href="#51" class="mim-tip-reference" title="Rojas, C. V. <strong>Personal Communication.</strong> Pittsburgh, Pa. 2/6/1992."None>Rojas (1992)</a> stated that the transition occurred at nucleotide 4774 and changed met to val at residue 1592 (M1592V). <a href="#25" class="mim-tip-reference" title="Heine, R., Pika, U., Lehmann-Horn, F. <strong>A novel SCN4A mutation causing myotonia aggravated by cold and potassium.</strong> Hum. Molec. Genet. 2: 1349-1353, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8242056/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8242056</a>] [<a href="https://doi.org/10.1093/hmg/2.9.1349" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8242056">Heine et al. (1993)</a> found the M1592V mutation in 6 families with a myotonic, nondystrophic form of HYPP. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8242056+1659668" 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="Kelly, P., Yang, W. S., Costigan, D., Farrell, M. A., Murphy, S., Hardiman, O. <strong>Paramyotonia congenita and hyperkalemic periodic paralysis associated with a met1592-to-val substitution in the skeletal muscle sodium channel alpha subunit--a large kindred with a novel phenotype.</strong> Neuromusc. Disord. 7: 105-111, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9131651/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9131651</a>] [<a href="https://doi.org/10.1016/s0960-8966(96)00429-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9131651">Kelly et al. (1997)</a> described a large kindred in which affected members were phenotypically heterogeneous with episodic potassium-sensitive paralysis as well as stiffness and weakness induced by exercise and cold, suggesting a combined paramyotonia congenita (PMC; <a href="/entry/168300">168300</a>)/HYPP phenotype. Affected members had a heterozygous M1592V mutation, and the authors commented on the phenotypic variation associated with this mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9131651" 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">rs121908544 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908544;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=rs121908544" 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=rs121908544" 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=RCV000006258 OR RCV000206951 OR RCV000255921 OR RCV001813736 OR RCV003989102" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006258, RCV000206951, RCV000255921, RCV001813736, RCV003989102" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006258...</a>
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<p>In a family with paramyotonia congenita (PMC; <a href="/entry/168300">168300</a>), <a href="#45" class="mim-tip-reference" title="Ptacek, L. J., George, A. L., Jr., Barchi, R. L., Griggs, R. C., Riggs, J. E., Robertson, M., Leppert, M. F. <strong>Mutations in an S4 segment of the adult skeletal muscle sodium channel cause paramyotonia congenita.</strong> Neuron 8: 891-897, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1316765/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1316765</a>] [<a href="https://doi.org/10.1016/0896-6273(92)90203-p" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1316765">Ptacek et al. (1992)</a> identified a heterozygous mutation in the SCN4A gene, resulting in an arg1448-to-cys (R1448C) substitution. This codon is a highly conserved residue in the S4 helix of domain IV in the adult skeletal muscle sodium channel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1316765" 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 2 other families with PMC, <a href="#45" class="mim-tip-reference" title="Ptacek, L. J., George, A. L., Jr., Barchi, R. L., Griggs, R. C., Riggs, J. E., Robertson, M., Leppert, M. F. <strong>Mutations in an S4 segment of the adult skeletal muscle sodium channel cause paramyotonia congenita.</strong> Neuron 8: 891-897, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1316765/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1316765</a>] [<a href="https://doi.org/10.1016/0896-6273(92)90203-p" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1316765">Ptacek et al. (1992)</a> found a heterozygous mutation in the same codon, resulting in an arg1448-to-his (R1448H) substitution (see <a href="#0004">603967.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1316765" 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 PARAMYOTONIA CONGENITA</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">rs121908545 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908545;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=rs121908545" 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=rs121908545" 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=RCV000006259 OR RCV000206992 OR RCV000517055 OR RCV000662289 OR RCV001775065 OR RCV002267600 OR RCV002288469 OR RCV003483425 OR RCV004734499" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006259, RCV000206992, RCV000517055, RCV000662289, RCV001775065, RCV002267600, RCV002288469, RCV003483425, RCV004734499" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006259...</a>
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<p>In 2 families with paramyotonia congenita (PMC; <a href="/entry/168300">168300</a>), <a href="#45" class="mim-tip-reference" title="Ptacek, L. J., George, A. L., Jr., Barchi, R. L., Griggs, R. C., Riggs, J. E., Robertson, M., Leppert, M. F. <strong>Mutations in an S4 segment of the adult skeletal muscle sodium channel cause paramyotonia congenita.</strong> Neuron 8: 891-897, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1316765/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1316765</a>] [<a href="https://doi.org/10.1016/0896-6273(92)90203-p" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1316765">Ptacek et al. (1992)</a> found a heterozygous mutation in the SCN4A gene, resulting in an arg1448-to-his (R1448H) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1316765" 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="#41" class="mim-tip-reference" title="Meyer-Kleine, C., Otto, M., Zoll, B., Koch, M. C. <strong>Molecular and genetic characterization of German families with paramyotonia congenita and demonstration of founder effect in the Ravensberg families.</strong> Hum. Genet. 93: 707-710, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8005599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8005599</a>] [<a href="https://doi.org/10.1007/BF00201577" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8005599">Meyer-Kleine et al. (1994)</a> found that the R1448H mutation is exceptionally frequent in the Ravensberger Land region of northwest Germany, where it exists on a specific SCN4A microsatellite haplotype, indicating a founder effect within this subpopulation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8005599" 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 PARAMYOTONIA CONGENITA/HYPERKALEMIC PERIODIC PARALYSIS</strong>
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SCN4A, ALA1156THR
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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> rs80338958 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338958;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/rs80338958?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=rs80338958" 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=rs80338958" 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=RCV000006260 OR RCV000020271 OR RCV000516392 OR RCV001004616 OR RCV002496281 OR RCV003162214 OR RCV004545720 OR RCV004595874" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006260, RCV000020271, RCV000516392, RCV001004616, RCV002496281, RCV003162214, RCV004545720, RCV004595874" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006260...</a>
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<p>In a family of Finnish extraction whose affected members displayed an unusual mixture of clinical features of both paramyotonia congenita (PMC; <a href="/entry/168300">168300</a>) and hyperkalemic periodic paralysis (HYPP; <a href="/entry/170500">170500</a>), <a href="#39" class="mim-tip-reference" title="McClatchey, A. I., McKenna-Yasek, D., Cros, D., Worthen, H. G., Kuncl, R. W., DeSilva, S. M., Cornblath, D. R., Gusella, J. F., Brown, R. H., Jr. <strong>Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel.</strong> Nature Genet. 2: 148-152, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1338909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1338909</a>] [<a href="https://doi.org/10.1038/ng1092-148" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1338909">McClatchey et al. (1992)</a> identified a heterozygous c.3466G-A transition in the SCN4A gene, resulting in an ala1156-to-thr (A1156T) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1338909" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 PARAMYOTONIA CONGENITA/MYOTONIA CONGENITA</strong>
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MYOTONIA FLUCTUANS, INCLUDED
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SCN4A, SER804PHE
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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> rs121908546 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908546;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/rs121908546?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=rs121908546" 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=rs121908546" 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=RCV000006261 OR RCV000489309 OR RCV001799586 OR RCV003505081" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006261, RCV000489309, RCV001799586, RCV003505081" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006261...</a>
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<p>In affected members of an Italian family with features of both paramyotonia congenita (PMC; <a href="/entry/168300">168300</a>) and myotonia congenita (see <a href="/entry/608390">608390</a>), <a href="#39" class="mim-tip-reference" title="McClatchey, A. I., McKenna-Yasek, D., Cros, D., Worthen, H. G., Kuncl, R. W., DeSilva, S. M., Cornblath, D. R., Gusella, J. F., Brown, R. H., Jr. <strong>Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel.</strong> Nature Genet. 2: 148-152, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1338909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1338909</a>] [<a href="https://doi.org/10.1038/ng1092-148" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1338909">McClatchey et al. (1992)</a> identified a heterozygous c.2411C-T transition in the SCN4A gene, resulting in a ser804-to-phe (S804F) substitution predicted to be in the cytoplasmic face of the sixth transmembrane segment of domain II. A serine had been present at this position in all sodium channels sequenced to that date. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1338909" 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="#49" class="mim-tip-reference" title="Ricker, K., Moxley, R. T., III, Heine, R., Lehmann-Horn, F. <strong>Myotonia fluctuans: a third type of muscle sodium channel disease.</strong> Arch. Neurol. 51: 1095-1102, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7980103/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7980103</a>] [<a href="https://doi.org/10.1001/archneur.1994.00540230033009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7980103">Ricker et al. (1994)</a> found the S804F mutation in a family with the 'myotonia fluctuans' (<a href="/entry/608390">608390</a>) phenotype. See also <a href="#0012">603967.0012</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7980103" 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 PARAMYOTONIA CONGENITA</strong>
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MYOTONIA, POTASSIUM-AGGRAVATED, INCLUDED
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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> rs80338792 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338792;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/rs80338792?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=rs80338792" 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=rs80338792" 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=RCV000006264 OR RCV000006265 OR RCV000479620 OR RCV000690377 OR RCV002267601 OR RCV005016246" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006264, RCV000006265, RCV000479620, RCV000690377, RCV002267601, RCV005016246" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006264...</a>
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<p>In a Belgian family with paramyotonia congenita (PMC; <a href="/entry/168300">168300</a>), <a href="#40" class="mim-tip-reference" title="McClatchey, A. I., Van den Bergh, P., Pericak-Vance, M. A., Raskind, W., Verellen, C., McKenna-Yasek, D., Rao, K., Haines, J. L., Bird, T., Brown, R. H., Jr., Gusella, J. F. <strong>Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita.</strong> Cell 68: 769-774, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1310898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1310898</a>] [<a href="https://doi.org/10.1016/0092-8674(92)90151-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1310898">McClatchey et al. (1992)</a> identified a heterozygous c.3917G-T transversion in the SCN4A gene, resulting in a gly1306-to-val (G1306V) substitution. The mutation affected a highly conserved residue in the III-IV cytoplasmic loop, a portion of the sodium channel thought to pivot in response to membrane depolarization, thereby blocking and inactivating the channel. Muscle weakness was not reported. The authors suggested that this is a temperature-sensitive mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1310898" 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="Lerche, H., Heine, R., Pika, U., George, A. L., Jr., Mitrovic, N., Browatzki, M., Weiss, T., Rivet-Bastide, M., Franke, C., Lomonaco, M., Ricker, K., Lehmann-Horn, F. <strong>Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III-IV linker.</strong> J. Physiol. 470: 13-22, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8308722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8308722</a>] [<a href="https://doi.org/10.1113/jphysiol.1993.sp019843" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8308722">Lerche et al. (1993)</a> identified a heterozygous G1306V substitution in a mother and son with potassium-aggravated myotonia (<a href="/entry/608390">608390</a>). Muscle stiffness in these individuals was also aggravated by exercise, but not by cold. Muscle weakness was not reported. Patch-clamp recordings on patient muscle samples showed slower sodium fast channel inactivation and an increase in late channel opening, resulting in a steady-state inward current, sustained muscle depolarization, and muscle fiber hyperexcitability. <a href="#34" class="mim-tip-reference" title="Lerche, H., Heine, R., Pika, U., George, A. L., Jr., Mitrovic, N., Browatzki, M., Weiss, T., Rivet-Bastide, M., Franke, C., Lomonaco, M., Ricker, K., Lehmann-Horn, F. <strong>Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III-IV linker.</strong> J. Physiol. 470: 13-22, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8308722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8308722</a>] [<a href="https://doi.org/10.1113/jphysiol.1993.sp019843" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8308722">Lerche et al. (1993)</a> identified different pathogenic mutations in the same codon (G1306A; <a href="#0012">603967.0012</a> and G1306E; <a href="#0025">603967.0025</a>) in other families with similar disorders, indicating that residue 1306 is important for sodium channel inactivation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8308722" 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="#14" 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> reported French Canadian patients with myotonia associated with the G1306V mutation. They had moderate myotonia with mild muscle hypertrophy. They noted exacerbation of symptoms with cold temperatures but no paradoxical myotonia. Female patients showed dramatic symptom improvement after menopause. <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>.0008 PARAMYOTONIA CONGENITA</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> rs121908547 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908547;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/rs121908547?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=rs121908547" 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=rs121908547" 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=RCV000006266 OR RCV000414134 OR RCV000540455 OR RCV000763019 OR RCV002267602 OR RCV003455986 OR RCV004532297 OR RCV004786239" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006266, RCV000414134, RCV000540455, RCV000763019, RCV002267602, RCV003455986, RCV004532297, RCV004786239" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006266...</a>
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<p>In a family with paramyotonia congenita (PMC; <a href="/entry/168300">168300</a>) living in North America, <a href="#40" class="mim-tip-reference" title="McClatchey, A. I., Van den Bergh, P., Pericak-Vance, M. A., Raskind, W., Verellen, C., McKenna-Yasek, D., Rao, K., Haines, J. L., Bird, T., Brown, R. H., Jr., Gusella, J. F. <strong>Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita.</strong> Cell 68: 769-774, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1310898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1310898</a>] [<a href="https://doi.org/10.1016/0092-8674(92)90151-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1310898">McClatchey et al. (1992)</a> identified a heterozygous C-to-T transition in the SCN4A gene, resulting in a thr1313-to-met (T1313M) substitution. The mutation affected a highly conserved residue in the III-IV cytoplasmic loop of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1310898" 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="#61" class="mim-tip-reference" title="Tahmoush, A. J., Schaller, K. L., Zhang, P., Hyslop, T., Heiman-Patterson, T., Caldwell, J. H. <strong>Muscle sodium channel inactivation defect in paramyotonia congenita with the thr1313-to-met mutation.</strong> Neuromusc. Disord. 4: 447-454, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7533571/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7533571</a>] [<a href="https://doi.org/10.1016/0960-8966(94)90083-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7533571">Tahmoush et al. (1994)</a> identified the T1313M mutation in a 3-generation paramyotonia congenita family with 5 affected individuals. Single-channel recordings of normal and abnormal sodium channels in myotubes in tissue-cultured muscles derived from the proband showed that abnormal sodium channels at 22 degrees centigrade exhibited long duration and late openings. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7533571" 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="#68" class="mim-tip-reference" title="Yamada, T., Ochi, H., Hara, H., Yoshimura, T., Kobayashi T. <strong>A skeletal muscle sodium channel mutation in a Japanese family with paramyotonia congenita.</strong> J. Neurol. Sci. 133: 192-193, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8583225/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8583225</a>] [<a href="https://doi.org/10.1016/0022-510x(95)00166-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8583225">Yamada et al. (1995)</a> found the same mutation in a Japanese woman and her son who had PMC manifested by difficulty in closure of eyelids or chewing, and stiffness and weakness in hands aggravated by cold beginning at about 7 years of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8583225" 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="#37" class="mim-tip-reference" title="Matthews, E., Manzur, A. Y., Sud, R., Muntoni, F., Hanna, M. G. <strong>Stridor as a neonatal presentation of skeletal muscle sodium channelopathy.</strong> Arch. Neurol. 68: 127-129, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21220685/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21220685</a>] [<a href="https://doi.org/10.1001/archneurol.2010.347" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21220685">Matthews et al. (2011)</a> reported a family with PMC due to the heterozygous T1313M mutation. Before correct diagnosis, the youngest affected individual presented with neonatal inspiratory stridor and poor feeding. Laryngoscopy showed findings consistent with laryngomalacia. He continued to have stridor for the first 6 months of life, and later motor milestones were mildly delayed. In early childhood, he was noted to have frequent episodic muscle weakness and stiffness associated with cold weather. At age 4 years, he continued to have episodes of inspiratory stridor exacerbated by viral illness, cold weather, and prolonged laughing or crying. His mother, grandfather, and great-uncle reported similar episodes of muscle stiffness and weakness exacerbated by cold and exercise. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21220685" 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, POTASSIUM-AGGRAVATED</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">rs121908548 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908548;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=rs121908548" 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=rs121908548" 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=RCV000006267 OR RCV000006268 OR RCV000518064 OR RCV000800365 OR RCV001849259" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006267, RCV000006268, RCV000518064, RCV000800365, RCV001849259" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006267...</a>
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<p>In a father and daughter (family SCM8) with potassium-aggravated myotonia (<a href="/entry/608390">608390</a>) without muscle weakness, <a href="#25" class="mim-tip-reference" title="Heine, R., Pika, U., Lehmann-Horn, F. <strong>A novel SCN4A mutation causing myotonia aggravated by cold and potassium.</strong> Hum. Molec. Genet. 2: 1349-1353, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8242056/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8242056</a>] [<a href="https://doi.org/10.1093/hmg/2.9.1349" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8242056">Heine et al. (1993)</a> identified a heterozygous c.4765G-A transition in exon 24 of the SCN4A gene, predicted to result in a val1589-to-met (V1589M) substitution. The family had previously been reported by <a href="#27" class="mim-tip-reference" title="Iaizzo, P. A., Franke, C., Hatt, H., Spittelmeister, W., Ricker, K., Rudel, R., Lehmann-Horn, F. <strong>Altered sodium channel behaviour causes myotonia in autosomal dominantly inherited myotonia congenita.</strong> Neuromusc. Disord. 1: 47-53, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1668369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1668369</a>] [<a href="https://doi.org/10.1016/0960-8966(91)90042-q" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1668369">Iaizzo et al. (1991)</a> as family MyC2. The myotonia in this family was aggravated by both cold and potassium loading, similar to paramyotonia congenita (PMC; <a href="/entry/168300">168300</a>). The mutation is located within transmembrane segment S6 of channel repeat IV close to the cytoplasmic surface, a region thought to act as acceptor of the inactivation gate of the channel. An increase in the number of noninactivating sodium channels had been demonstrated in earlier electrophysiologic studies on excised muscle from the index patient. The nearby M1592V (<a href="#0002">603967.0002</a>) mutation causes hyperkalemic periodic paralysis (<a href="/entry/170500">170500</a>) of the myotonic, nondystrophic form. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1668369+8242056" 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="#43" class="mim-tip-reference" title="Orrell, R. W., Jurkat-Rott, K., Lehmann-Horn, F., Lane, R. J. M. <strong>Familial cramp due to potassium-aggravated myotonia.</strong> J. Neurol. Neurosurg. Psychiat. 65: 569-572, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9771789/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9771789</a>] [<a href="https://doi.org/10.1136/jnnp.65.4.569" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9771789">Orrell et al. (1998)</a> identified the V1589M mutation in a family in which 9 members spanning 4 generations had cramps in the fingers, toes, and eyelids, consistent with potassium-aggravated myotonia. A reduction in amplitude of compound muscle action potential on cooling and administration of potassium was demonstrated. The authors noted that the phenotype in this family was milder than that in the family reported by <a href="#25" class="mim-tip-reference" title="Heine, R., Pika, U., Lehmann-Horn, F. <strong>A novel SCN4A mutation causing myotonia aggravated by cold and potassium.</strong> Hum. Molec. Genet. 2: 1349-1353, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8242056/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8242056</a>] [<a href="https://doi.org/10.1093/hmg/2.9.1349" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8242056">Heine et al. (1993)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9771789+8242056" 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">rs121908549 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908549;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=rs121908549" 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=rs121908549" 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=RCV000006269 OR RCV000497702 OR RCV003505082" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006269, RCV000497702, RCV003505082" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006269...</a>
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<p>In a patient with acetazolamide-responsive myotonia congenita without periodic paralysis (see <a href="/entry/608390">608390</a>), <a href="#48" class="mim-tip-reference" title="Ptacek, L. J., Tawil, R., Griggs, R. C., Meola, G., McManis, P., Barohn, R. J., Mendell, J. R., Harris, C., Spitzer, R., Santiago, F., Leppert, M. F. <strong>Sodium channel mutations in acetazolamide-responsive myotonia congenita, paramyotonia congenita, and hyperkalemic periodic paralysis.</strong> Neurology 44: 1500-1503, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8058156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8058156</a>] [<a href="https://doi.org/10.1212/wnl.44.8.1500" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8058156">Ptacek et al. (1994)</a> identified a heterozygous c.3555A-G transition in the SCN4A gene, predicted to result in an ile1160-to-val (I1160V) substitution. This isoleucine is a highly conserved residue, cosegregated with the disease phenotype in one studied kindred, and was not present in samples from 100 unrelated unaffected individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8058156" 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 PARAMYOTONIA CONGENITA</strong>
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SCN4A, LEU1433ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908550 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908550;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=rs121908550" 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=rs121908550" 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=RCV000006270 OR RCV002267603" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006270, RCV002267603" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006270...</a>
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<p><a href="#47" class="mim-tip-reference" title="Ptacek, L. J., Gouw, L., Kwiencinski, H., McManis, P., Mendell, J. R., Barohn, A. L., Jr., Robertson, M., Leppert, M. F. <strong>Sodium channel mutations in paramyotonia congenita and hyperkalemic periodic paralysis.</strong> Ann. Neurol. 33: 300-307, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8388676/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8388676</a>] [<a href="https://doi.org/10.1002/ana.410330312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8388676">Ptacek et al. (1993)</a> reported that a heterozygous leu-to-arg (L1433R) change in the SCN4A gene results in the paramyotonia congenita (PMC; <a href="/entry/168300">168300</a>) phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8388676" 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="0012" class="mim-anchor"></a>
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<strong>.0012 MYOTONIA FLUCTUANS</strong>
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SCN4A, GLY1306ALA
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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> rs80338792 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338792;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/rs80338792?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=rs80338792" 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=rs80338792" 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=RCV000153907 OR RCV000525753 OR RCV001535772 OR RCV001799587 OR RCV002288470" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000153907, RCV000525753, RCV001535772, RCV001799587, RCV002288470" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000153907...</a>
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<p>In affected members of 3 families with a muscle sodium channel disorder termed 'myotonia fluctuans' (see <a href="/entry/608390">608390</a>), <a href="#49" class="mim-tip-reference" title="Ricker, K., Moxley, R. T., III, Heine, R., Lehmann-Horn, F. <strong>Myotonia fluctuans: a third type of muscle sodium channel disease.</strong> Arch. Neurol. 51: 1095-1102, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7980103/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7980103</a>] [<a href="https://doi.org/10.1001/archneur.1994.00540230033009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7980103">Ricker et al. (1994)</a> identified a heterozygous c.3917G-C transversion in exon 22 of the SCN4A gene, resulting in a gly1306-to-ala (G1306A) substitution. The mutation resides in the region of the sodium channel protein containing the cytoplasmic loop between domains 3 and 4. The phenotype consists of fluctuating myotonia of varying severity, a warm-up phenomenon, worsening of myotonia after potassium loading, increased myotonia of delayed onset following exercise, and no significant increase of myotonia following exposure to cold. Muscle weakness did not occur. One other family with the same phenotype had a previously described mutation of the sodium channel (<a href="#0006">603967.0006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7980103" 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="Lerche, H., Heine, R., Pika, U., George, A. L., Jr., Mitrovic, N., Browatzki, M., Weiss, T., Rivet-Bastide, M., Franke, C., Lomonaco, M., Ricker, K., Lehmann-Horn, F. <strong>Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III-IV linker.</strong> J. Physiol. 470: 13-22, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8308722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8308722</a>] [<a href="https://doi.org/10.1113/jphysiol.1993.sp019843" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8308722">Lerche et al. (1993)</a> identified the G1306A mutation in a patient with myotonia fluctuans. Patch-clamp recordings on patient muscle samples showed slower sodium fast channel inactivation and an increase in late channel opening, resulting in a steady-state inward current, sustained muscle depolarization, and muscle fiber hyperexcitability. <a href="#34" class="mim-tip-reference" title="Lerche, H., Heine, R., Pika, U., George, A. L., Jr., Mitrovic, N., Browatzki, M., Weiss, T., Rivet-Bastide, M., Franke, C., Lomonaco, M., Ricker, K., Lehmann-Horn, F. <strong>Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III-IV linker.</strong> J. Physiol. 470: 13-22, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8308722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8308722</a>] [<a href="https://doi.org/10.1113/jphysiol.1993.sp019843" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8308722">Lerche et al. (1993)</a> identified different pathogenic mutations in the same codon (G1306V; <a href="#0007">603967.0007</a> and G1306E; <a href="#0025">603967.0025</a>) in other families with similar disorders, indicating that residue 1306 is important for sodium channel inactivation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8308722" 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="0013" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0013 PARAMYOTONIA CONGENITA</strong>
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SCN4A, VAL1293ILE
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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> rs121908551 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908551;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/rs121908551?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=rs121908551" 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=rs121908551" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006272 OR RCV000396578 OR RCV000509130 OR RCV000654659" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006272, RCV000396578, RCV000509130, RCV000654659" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006272...</a>
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<p>In 3 unrelated 3-generation families segregating paramyotonia without cold paralysis (see <a href="/entry/168300">168300</a>) as an autosomal dominant trait, <a href="#31" class="mim-tip-reference" title="Koch, M. C., Baumbach, K., George, A. L., Ricker, K. <strong>Paramyotonia congenita without paralysis on exposure to cold: a novel mutation in the SCN4A gene (val1293ile).</strong> Neuroreport 6: 2001-2004, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8580427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8580427</a>] [<a href="https://doi.org/10.1097/00001756-199510010-00012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8580427">Koch et al. (1995)</a> identified a heterozygous c.3877G-A transition in exon 21 of the SCN4A gene, resulting in a val1293-to-ile (V1293I) substitution. The amino acid alteration was not found to be a mild polymorphism in their survey of 200 chromosomes from the German population. The predicted mutation was located at the intracellular phase of segment S6 in domain III of the channel protein. Val1293 is conserved in human, rat, and eel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8580427" 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="0014" class="mim-anchor"></a>
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<strong>.0014 MYOTONIA CONGENITA, ATYPICAL</strong>
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SCN4A, VAL445MET
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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> rs121908552 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908552;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/rs121908552?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=rs121908552" 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=rs121908552" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006273 OR RCV000255075 OR RCV000544236 OR RCV000763021 OR RCV002267604" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006273, RCV000255075, RCV000544236, RCV000763021, RCV002267604" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006273...</a>
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<p><a href="#52" class="mim-tip-reference" title="Rosenfeld, J., Sloan-Brown, K., George, A. L., Jr. <strong>A novel muscle sodium channel mutation causes painful congenital myotonia.</strong> Ann. Neurol. 42: 811-814, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9392583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9392583</a>] [<a href="https://doi.org/10.1002/ana.410420520" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9392583">Rosenfeld et al. (1997)</a> reported the first known mutation in the first repeat domain (D1) of the SCN4A gene. The previous conspicuous absence of mutations in this region fueled speculation that mutations in this domain were either inconsequential or possibly lethal. The heterozygous mutation, val445-to-met (V445M), was associated with an unusual form of painful congenital myotonia (see <a href="/entry/608390">608390</a>). The distinctive phenotype suggested that the pattern of sodium channel dysfunction might also be unique. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9392583" 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="#65" class="mim-tip-reference" title="Wang, D. W., VanDeCarr, D., Ruben, P. C., George, A. L., Jr., Bennett, P. B. <strong>Functional consequences of a domain 1/S6 segment sodium channel mutation associated with painful congenital myotonia.</strong> FEBS Lett. 448: 231-234, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10218481/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10218481</a>] [<a href="https://doi.org/10.1016/s0014-5793(99)00338-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10218481">Wang et al. (1999)</a> characterized the V445M mutation using heterologous expression of recombinant mutant and wildtype skeletal muscle sodium channel alpha subunits. Their findings established that the mutation causes a defect in sodium channel gating that is compatible with a myotonia-producing lesion. The pattern of dysfunction was distinct from other muscle sodium channel mutations, supporting the notion that D1 sodium channel mutations may be associated with unusual phenotypes. They also demonstrated that flecainide effectively suppressed the abnormal channel behavior, consistent with the observed clinical efficacy of the drug in treating the unusual form of myotonia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10218481" 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="#14" 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> reported French Canadian patients with the V445M mutation. The phenotype was characterized by severe and painful generalized myotonia and severe muscle hypertrophy. Ethanol or mexiletine significantly alleviated myotonia in 1 patient. <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"><span class="text-primary">●</span> rs80338784 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338784;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/rs80338784?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=rs80338784" 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=rs80338784" 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=RCV000006274 OR RCV000206926 OR RCV003482224 OR RCV005016247" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006274, RCV000206926, RCV003482224, RCV005016247" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006274...</a>
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<p><a href="#8" class="mim-tip-reference" title="Bulman, D. E., Scoggan, K. A., van Oene, M. D., Nicolle, M. W., Hahn, A. F., Tollar, L. L., Ebers, G. C. <strong>A novel sodium channel mutation in a family with hypokalemic periodic paralysis.</strong> Neurology 53: 1932-1936, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10599760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10599760</a>] [<a href="https://doi.org/10.1212/wnl.53.9.1932" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10599760">Bulman et al. (1999)</a> found a heterozygous arg669-to-his (R669H) mutation in the SCN4A gene in a family in which 4 members had hypokalemic periodic paralysis type 2 (HOKPP2; <a href="/entry/613345">613345</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10599760" 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 in vitro studies, <a href="#32" class="mim-tip-reference" title="Kuzmenkin, A., Muncan, V., Jurkat-Rott, K., Hang, C., Lerche, H., Lehmann-Horn, F., Mitrovic, N. <strong>Enhanced inactivation and pH sensitivity of Na+ channel mutations causing hypokalemic periodic paralysis type II.</strong> Brain 125: 835-843, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11912116/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11912116</a>] [<a href="https://doi.org/10.1093/brain/awf071" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11912116">Kuzmenkin et al. (2002)</a> showed that the R669H mutation caused enhanced fast and slow inactivation of the SCN4A sodium channel. The inactivation defect could be alleviated by decreased pH, which may explain why some patients have relief by some physical exercise. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11912116" 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> rs80338788 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338788;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/rs80338788?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=rs80338788" 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=rs80338788" 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=RCV000006275 OR RCV000206975 OR RCV001532353 OR RCV002490327 OR RCV003387718 OR RCV004798719" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006275, RCV000206975, RCV001532353, RCV002490327, RCV003387718, RCV004798719" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006275...</a>
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<p>In affected members of 3 unrelated families (HypoPP29, HypoPP18, and HypoPP105) with hypokalemic periodic paralysis type 2 (HOKPP2; <a href="/entry/613345">613345</a>), <a href="#28" class="mim-tip-reference" title="Jurkat-Rott, K., Mitrovic, N., Hang, C., Kouzmekine, A., Iaizzo, P., Herzog, J., Lerche, H., Nicole, S., Vale-Santos, J., Chauveau, D., Fontaine, B., Lehmann-Horn, F. <strong>Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current.</strong> Proc. Nat. Acad. Sci. 97: 9549-9554, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10944223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10944223</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10944223[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.97.17.9549" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10944223">Jurkat-Rott et al. (2000)</a> identified a heterozygous c.2016G-A transition in exon 12 of the SCN4A gene, resulting in an arg672-to-his (R672H) substitution in the voltage sensor of domain-2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10944223" 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 in vitro studies in HEK293 cells, <a href="#32" class="mim-tip-reference" title="Kuzmenkin, A., Muncan, V., Jurkat-Rott, K., Hang, C., Lerche, H., Lehmann-Horn, F., Mitrovic, N. <strong>Enhanced inactivation and pH sensitivity of Na+ channel mutations causing hypokalemic periodic paralysis type II.</strong> Brain 125: 835-843, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11912116/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11912116</a>] [<a href="https://doi.org/10.1093/brain/awf071" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11912116">Kuzmenkin et al. (2002)</a> showed that the R672H mutation caused enhanced fast inactivation of the SCN4A sodium channel. The inactivation defect could be alleviated by decreased pH, which may explain why some patients have relief by some physical exercise. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11912116" 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 HYPOKALEMIC PERIODIC PARALYSIS, TYPE 2</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006276 OR RCV000020262 OR RCV000206901 OR RCV001092728" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006276, RCV000020262, RCV000206901, RCV001092728" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006276...</a>
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<p>In affected members of 2 multigenerational families (HypoPP106 and HypoPP6) with hypokalemic periodic paralysis type 2 (HOKPP2; <a href="/entry/613345">613345</a>), <a href="#28" class="mim-tip-reference" title="Jurkat-Rott, K., Mitrovic, N., Hang, C., Kouzmekine, A., Iaizzo, P., Herzog, J., Lerche, H., Nicole, S., Vale-Santos, J., Chauveau, D., Fontaine, B., Lehmann-Horn, F. <strong>Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current.</strong> Proc. Nat. Acad. Sci. 97: 9549-9554, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10944223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10944223</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10944223[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.97.17.9549" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10944223">Jurkat-Rott et al. (2000)</a> identified a heterozygous c.2015C-G transversion in the SCN4A gene, resulting in an arg672-to-gly (R672G) substitution in the voltage sensor of domain-2. Excised skeletal muscle fibers from a patient heterozygous for R672G displayed depolarization and weakness in low-potassium extracellular solution. Slowing and smaller size of action potentials were suggestive of excitability of the wildtype channel population only. Alterations found were decisive for the pathogenesis of episodic muscle weakness by reducing the number of excitable sodium channels, particularly at sustained membrane depolarization. This form of the disease was caused by enhanced channel inactivation and current reduction, and showed no myotonia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10944223" 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 in vitro studies in HEK293 cells, <a href="#32" class="mim-tip-reference" title="Kuzmenkin, A., Muncan, V., Jurkat-Rott, K., Hang, C., Lerche, H., Lehmann-Horn, F., Mitrovic, N. <strong>Enhanced inactivation and pH sensitivity of Na+ channel mutations causing hypokalemic periodic paralysis type II.</strong> Brain 125: 835-843, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11912116/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11912116</a>] [<a href="https://doi.org/10.1093/brain/awf071" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11912116">Kuzmenkin et al. (2002)</a> showed that the R672G mutation caused enhanced slow and fast inactivation of the SCN4A sodium channel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11912116" 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 MYASTHENIC SYNDROME, CONGENITAL, 16</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">rs121908553 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908553;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=rs121908553" 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=rs121908553" 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=RCV000006277 OR RCV000235023" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006277, RCV000235023" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006277...</a>
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<p>In a patient with a congenital myasthenic syndrome-16 (CMS16; <a href="/entry/614198">614198</a>) associated with fatigable generalized weakness and recurrent attacks of respiratory and bulbar paralysis since birth, <a href="#62" class="mim-tip-reference" title="Tsujino, A., Maertens, C., Ohno, K., Shen, X.-M., Fukuda, T., Harper, C. M., Cannon, S. C., Engel, A. G. <strong>Myasthenic syndrome caused by mutation of the SCN4A sodium channel.</strong> Proc. Nat. Acad. Sci. 100: 7377-7382, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12766226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12766226</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12766226[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.1230273100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12766226">Tsujino et al. (2003)</a> detected compound heterozygosity for 2 variants in the SCN4A gene involving conserved residues not present in 400 normal alleles: a c.4325T-A transversion, resulting in a val1442-to-glu (V1442E) substitution in the S3/S4 extracellular linker in domain IV, and a c.737C-T transition, resulting in a ser246-to-leu (S246L; <a href="#0031">603967.0031</a>) change in the S4/S5 cytoplasmic linker in domain I. The genetically engineered V1442E sodium channel expressed in cultured cells showed marked enhancement of fast inactivation close to the resting potential, and enhanced use-dependent inactivation on high-frequency stimulation. The proband's asymptomatic mother and sister were heterozygous for the S246L mutation. Paternal DNA was unavailable for analysis. The authors considered S246L likely to be a benign polymorphism, whereas the V1442E mutation defines a novel disease mechanism and a novel phenotype with myasthenic features. <a href="#62" class="mim-tip-reference" title="Tsujino, A., Maertens, C., Ohno, K., Shen, X.-M., Fukuda, T., Harper, C. M., Cannon, S. C., Engel, A. G. <strong>Myasthenic syndrome caused by mutation of the SCN4A sodium channel.</strong> Proc. Nat. Acad. Sci. 100: 7377-7382, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12766226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12766226</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12766226[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.1230273100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12766226">Tsujino et al. (2003)</a> concluded that the inheritance pattern of this congenital myasthenic syndrome could not be unambiguously established. They suggested that the more severe V1442E mutation may be dominant, but it could not be proven because the mutation was observed only in combination with S246L on the other chromosome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12766226" 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 PARAMYOTONIA CONGENITA</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">rs121908554 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908554;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=rs121908554" 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=rs121908554" 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=RCV000006278" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006278" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006278</a>
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<p>In a large Japanese family with paramyotonia congenita (PMC; <a href="/entry/168300">168300</a>), <a href="#56" class="mim-tip-reference" title="Sasaki, R., Takano, H., Kamakura, K., Kaida, K., Hirata, A., Saito, M., Tanaka, H., Kuzuhara, S., Tsuji, S. <strong>A novel mutation in the gene for the adult skeletal muscle sodium channel alpha-subunit (SCN4A) that causes paramyotonia congenita of von Eulenburg.</strong> Arch. Neurol. 56: 692-696, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369308/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369308</a>] [<a href="https://doi.org/10.1001/archneur.56.6.692" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10369308">Sasaki et al. (1999)</a> identified a heterozygous c.4367G-A change in exon 24 of the SCN4A gene, resulting in a gly1456-to-glu (G1456E) substitution in S4 of domain IV of the channel. Only 3 of 9 affected members reported episodes of severe generalized weakness, which were always after cold exposure. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10369308" 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 with PMC without periodic paralysis, which the authors termed 'pure paramyotonia,' <a href="#12" class="mim-tip-reference" title="Davies, N. P., Eunson, L. H., Gregory, R. P., Mills, K. R., Morrison, P. J., Hanna, M. G. <strong>Clinical, electrophysiological, and molecular genetic studies in a new family with paramyotonia congenita.</strong> J. Neurol. Neurosurg. Psychiat. 68: 504-507, 2000. Note: Erratum: J. Neurol. Neurosurg. Psychiat. 69: 139 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10727489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10727489</a>] [<a href="https://doi.org/10.1136/jnnp.68.4.504" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10727489">Davies et al. (2000)</a> identified the G1456E mutation. The authors predicted that the mutation would impair voltage sensing or channel inactivation in a temperature-dependent fashion and concluded that exon 24 is a hotspot for paramyotonia mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10727489" 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 HYPOKALEMIC PERIODIC PARALYSIS, TYPE 2</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">rs80338785 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338785;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=rs80338785" 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=rs80338785" 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=RCV000006279 OR RCV000206986 OR RCV003493408" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006279, RCV000206986, RCV003493408" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006279...</a>
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<p>In the proband of a family with hypokalemic periodic paralysis type 2 (HOKPP2; <a href="/entry/613345">613345</a>), <a href="#13" class="mim-tip-reference" title="Davies, N. P., Eunson, L. H., Samuel, M., Hanna, M. G. <strong>Sodium channel gene mutations in hypokalemic periodic paralysis: an uncommon cause in the UK.</strong> Neurology 57: 1323-1325, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11591859/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11591859</a>] [<a href="https://doi.org/10.1212/wnl.57.7.1323" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11591859">Davies et al. (2001)</a> identified a heterozygous c.2014C-A change in exon 12 of the SCN4A gene, resulting in an arg672-to-ser (R672S) substitution. The patient responded well to acetazolamide. The authors noted that 2 other mutations in the same codon had been reported in HOKPP (see <a href="#0016">603967.0016</a> and <a href="#0017">603967.0017</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11591859" 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>Functional expression studies of the R672S sodium channel by <a href="#3" class="mim-tip-reference" title="Bendahhou, S., Cummins, T. R., Griggs, R. C., Fu, Y.-H., Ptacek, L. J. <strong>Sodium channel inactivation defects are associated with acetazolamide-exacerbated hypokalemic periodic paralysis.</strong> Ann. Neurol. 50: 417-420, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11558801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11558801</a>] [<a href="https://doi.org/10.1002/ana.1144" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11558801">Bendahhou et al. (2001)</a> showed a small but significant hyperpolarizing shift in the steady-state fast inactivation, and a dramatic enhancement in channel slow inactivation. The defects are mainly due to a slow recovery of the mutant channels from inactivation. The authors noted that their patient with this mutation had shown a worsening of symptoms from acetazolamide. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11558801" 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="#63" class="mim-tip-reference" title="Venance, S. L., Jurkat-Rott, K., Lehmann-Horn, F., Tawil, R. <strong>SCN4A-associated hypokalemic periodic paralysis merits a trial of acetazolamide.</strong> Neurology 63: 1977 only, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15557532/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15557532</a>] [<a href="https://doi.org/10.1212/01.wnl.0000143068.99794.5b" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15557532">Venance et al. (2004)</a> reported a sporadic patient with HOKPP and the R672S mutation who responded well to acetazolamide. The authors noted the variability in response to the drug and suggested that carbonic anhydrase inhibitors should be considered in patients with HOKPP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15557532" 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>.0021 HYPOKALEMIC PERIODIC PARALYSIS, TYPE 2</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">rs121908555 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908555;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=rs121908555" 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=rs121908555" 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=RCV000006280 OR RCV000713100 OR RCV001210018 OR RCV002512825" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006280, RCV000713100, RCV001210018, RCV002512825" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006280...</a>
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<p>In a Japanese family with an unusual form of hypokalemic periodic paralysis type 2 (HOKPP2; <a href="/entry/613345">613345</a>), <a href="#59" class="mim-tip-reference" title="Sugiura, Y., Aoki, T., Sugiyama, Y., Hida, C., Ogata, M., Yamamoto, T. <strong>Temperature-sensitive sodium channelopathy with heat-induced myotonia and cold-induced paralysis.</strong> Neurology 54: 2179-2181, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10851391/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10851391</a>] [<a href="https://doi.org/10.1212/wnl.54.11.2179" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10851391">Sugiura et al. (2000)</a> identified a heterozygous c.3472C-T transition in exon 19 of the SCN4A gene, resulting in a pro1158-to-ser (P1158S) substitution between the fourth and fifth transmembrane segments of domain III. The phenotype in this family was unusual in that affected members showed heat-induced myotonia and cold-induced paralysis with hypokalemia. Myotonia lessened with exercise and was alleviated by cold, thus distinguishing the myotonia from paramyotonia congenita (PMC; <a href="/entry/168300">168300</a>). Treatment with acetazolamide alleviated the myotonia, but slightly worsened the paralysis. Patients showed seasonal swings with myotonia in the summer and paralysis in the winter, with hypokalemia during the paralytic attacks. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10851391" 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 studies, <a href="#60" class="mim-tip-reference" title="Sugiura, Y., Makita, N., Li, L., Noble, P. J., Kimura, J., Kumagai, Y., Soeda, T., Yamamoto, T. <strong>Cold induces shifts of voltage dependence in mutant SCN4A, causing hypokalemic periodic paralysis.</strong> Neurology 61: 914-918, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14557559/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14557559</a>] [<a href="https://doi.org/10.1212/01.wnl.0000086820.54065.a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14557559">Sugiura et al. (2003)</a> showed that the P1158S mutation exhibited temperature-dependent negative shifts in the voltage dependence of activation and inactivation as well as a slower rate of inactivation compared to wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14557559" 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 NORMOKALEMIC PERIODIC PARALYSIS, POTASSIUM-SENSITIVE</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> rs121908556 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908556;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/rs121908556?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=rs121908556" 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=rs121908556" 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=RCV000006281 OR RCV000206909 OR RCV001172114 OR RCV001813957" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006281, RCV000206909, RCV001172114, RCV001813957" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006281...</a>
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<p>In 5 affected members of a family with potassium-sensitive normokalemic periodic paralysis (see HYPP, <a href="/entry/170500">170500</a>), <a href="#64" class="mim-tip-reference" title="Vicart, S., Sternberg, D., Fournier, E., Ochsner, F., Laforet, P., Kuntzer, T., Eymard, B., Hainque, B., Fontaine, B. <strong>New mutations of SCN4A cause a potassium-sensitive normokalemic periodic paralysis.</strong> Neurology 63: 2120-2127, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15596759/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15596759</a>] [<a href="https://doi.org/10.1212/01.wnl.0000145768.09934.ec" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15596759">Vicart et al. (2004)</a> identified a heterozygous C-to-G transversion in exon 13 of the SCN4A gene, resulting in an arg675-to-gly (R675G) substitution within the membrane-spanning segment S4 of domain II of the protein, which is known to be involved in the voltage sensing of the channel. Acetazolamide therapy was effective in almost all patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15596759" 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="#64" class="mim-tip-reference" title="Vicart, S., Sternberg, D., Fournier, E., Ochsner, F., Laforet, P., Kuntzer, T., Eymard, B., Hainque, B., Fontaine, B. <strong>New mutations of SCN4A cause a potassium-sensitive normokalemic periodic paralysis.</strong> Neurology 63: 2120-2127, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15596759/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15596759</a>] [<a href="https://doi.org/10.1212/01.wnl.0000145768.09934.ec" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15596759">Vicart et al. (2004)</a> noted that mutations affecting codon 672--R672H (<a href="#0016">603967.0016</a>), R672G (<a href="#0017">603967.0017</a>), and R672S (<a href="#0020">603967.0020</a>)--and codon 669 (R669H; <a href="#0015">603967.0015</a>) affect 2 nearby arginines in segment S4 of domain II and lead to hypokalemic periodic paralysis type 2 (HOKPP2; <a href="/entry/613345">613345</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15596759" 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>.0023 NORMOKALEMIC PERIODIC PARALYSIS, POTASSIUM-SENSITIVE</strong>
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SCN4A, ARG675GLN
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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> rs121908557 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908557;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/rs121908557?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=rs121908557" 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=rs121908557" 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=RCV000006282 OR RCV000206996 OR RCV000516541 OR RCV000543491 OR RCV003147276 OR RCV003335018 OR RCV005025013" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006282, RCV000206996, RCV000516541, RCV000543491, RCV003147276, RCV003335018, RCV005025013" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006282...</a>
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<p>In affected members of a family with potassium-sensitive normokalemic periodic paralysis (see HYPP, <a href="/entry/170500">170500</a>), <a href="#64" class="mim-tip-reference" title="Vicart, S., Sternberg, D., Fournier, E., Ochsner, F., Laforet, P., Kuntzer, T., Eymard, B., Hainque, B., Fontaine, B. <strong>New mutations of SCN4A cause a potassium-sensitive normokalemic periodic paralysis.</strong> Neurology 63: 2120-2127, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15596759/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15596759</a>] [<a href="https://doi.org/10.1212/01.wnl.0000145768.09934.ec" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15596759">Vicart et al. (2004)</a> identified a heterozygous arg675-to-gln (R675Q) substitution in the SCN4A gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15596759" 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="0024" class="mim-anchor"></a>
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<strong>.0024 NORMOKALEMIC PERIODIC PARALYSIS, POTASSIUM-SENSITIVE</strong>
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SCN4A, ARG675TRP
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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> rs121908556 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908556;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/rs121908556?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=rs121908556" 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=rs121908556" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006263 OR RCV000206954 OR RCV000713092 OR RCV001254163" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006263, RCV000206954, RCV000713092, RCV001254163" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006263...</a>
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<p>In affected members of a family with potassium-sensitive normokalemic periodic paralysis (see HYPP, <a href="/entry/170500">170500</a>), <a href="#64" class="mim-tip-reference" title="Vicart, S., Sternberg, D., Fournier, E., Ochsner, F., Laforet, P., Kuntzer, T., Eymard, B., Hainque, B., Fontaine, B. <strong>New mutations of SCN4A cause a potassium-sensitive normokalemic periodic paralysis.</strong> Neurology 63: 2120-2127, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15596759/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15596759</a>] [<a href="https://doi.org/10.1212/01.wnl.0000145768.09934.ec" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15596759">Vicart et al. (2004)</a> identified a heterozygous arg675-to-trp (R675W) mutation in the SCN4A gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15596759" 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="0025" class="mim-anchor"></a>
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<strong>.0025 MYOTONIA PERMANENS</strong>
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SCN4A, GLY1306GLU
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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> rs80338792 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338792;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/rs80338792?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=rs80338792" 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=rs80338792" 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=RCV000489251 OR RCV000552020 OR RCV001799588 OR RCV001823093 OR RCV002225070 OR RCV002490328 OR RCV004786240" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000489251, RCV000552020, RCV001799588, RCV001823093, RCV002225070, RCV002490328, RCV004786240" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000489251...</a>
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<p>In a woman with severe myotonia permanens (<a href="/entry/608390">608390</a>), <a href="#34" class="mim-tip-reference" title="Lerche, H., Heine, R., Pika, U., George, A. L., Jr., Mitrovic, N., Browatzki, M., Weiss, T., Rivet-Bastide, M., Franke, C., Lomonaco, M., Ricker, K., Lehmann-Horn, F. <strong>Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III-IV linker.</strong> J. Physiol. 470: 13-22, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8308722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8308722</a>] [<a href="https://doi.org/10.1113/jphysiol.1993.sp019843" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8308722">Lerche et al. (1993)</a> identified a heterozygous c.3917G-A transition in the SCN4A gene, resulting in a gly1306-to-glu (G1306E) substitution in the III-IV linker region of the protein. Patch-clamp recordings on patient muscle samples showed slower sodium fast channel inactivation and an increase in late channel opening, resulting in a steady-state inward current, sustained muscle depolarization, and muscle fiber hyperexcitability. <a href="#34" class="mim-tip-reference" title="Lerche, H., Heine, R., Pika, U., George, A. L., Jr., Mitrovic, N., Browatzki, M., Weiss, T., Rivet-Bastide, M., Franke, C., Lomonaco, M., Ricker, K., Lehmann-Horn, F. <strong>Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III-IV linker.</strong> J. Physiol. 470: 13-22, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8308722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8308722</a>] [<a href="https://doi.org/10.1113/jphysiol.1993.sp019843" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8308722">Lerche et al. (1993)</a> identified different pathogenic mutations in the same codon (G1306V; <a href="#0007">603967.0007</a> and G1306A; <a href="#0012">603967.0012</a>) in other families with similar disorders, indicating that residue 1306 is important for sodium channel inactivation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8308722" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Colding-Jorgensen, E., Duno, M., Vissing, J. <strong>Autosomal dominant monosymptomatic myotonia permanens.</strong> Neurology 67: 153-155, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16832098/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16832098</a>] [<a href="https://doi.org/10.1212/01.wnl.0000223838.88872.da" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16832098">Colding-Jorgensen et al. (2006)</a> identified a heterozygous G1306E substitution in a father and son with myotonia permanens. The authors noted that the mutation may interfere with the channel voltage sensor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16832098" 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="0026" class="mim-anchor"></a>
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<strong>.0026 PARAMYOTONIA CONGENITA</strong>
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SCN4A, MET1476ILE
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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> rs121908559 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908559;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/rs121908559?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=rs121908559" 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=rs121908559" 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=RCV000006284 OR RCV001046179 OR RCV001781191 OR RCV003323353" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006284, RCV001046179, RCV001781191, RCV003323353" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006284...</a>
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<p>In 44 patients from 11 French Canadian families with a myotonia phenotype most consistent with paramyotonia congenita (PMC; <a href="/entry/168300">168300</a>), <a href="#53" class="mim-tip-reference" title="Rossignol, E., Mathieu, J., Thiffault, I., Tetreault, M., Dicaire, M.-J., Chrestian, N., Dupre, N., Puymirat, J., Brais, B. <strong>A novel founder SCN4A mutation causes painful cold-induced myotonia in French-Canadians.</strong> Neurology 69: 1937-1941, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17998485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17998485</a>] [<a href="https://doi.org/10.1212/01.wnl.0000290831.08585.2c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17998485">Rossignol et al. (2007)</a> identified a heterozygous 4428G-A transition in the SCN4A gene, resulting in a met1476-to-ile (M1476I) substitution in a highly conserved residue of the domain IV cytoplasmic loop, which is known to be involved in fast inactivation. The patients originated from the Saguenay-Lac-Saint-Jean region with notable clustering around Saint-Felicien. Haplotype analysis indicated a founder effect. The phenotype was quite variable, with age at onset ranging from 5 to 67 years (mean, 21 years) and mild to severe symptoms. Eleven (25%) patients were asymptomatic despite myotonic discharges on EMG. The most consistent features were cold-induced myotonia (41%) and painful myotonia (18%). Potassium challenge was not conducted. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17998485" 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>.0027 PARAMYOTONIA CONGENITA/HYPERKALEMIC PERIODIC PARALYSIS</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">rs121908560 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908560;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=rs121908560" 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=rs121908560" 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=RCV000006285 OR RCV003996078" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006285, RCV003996078" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006285...</a>
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<p>In a female infant with severe fatal neonatal nondystrophic myotonia with overlapping features of paramyotonia congenita (PMC; <a href="/entry/168300">168300</a>) and hyperkalemic periodic paralysis (HYPP; <a href="/entry/170500">170500</a>), <a href="#18" class="mim-tip-reference" title="Gay, S., Dupuis, D., Faivre, L., Masurel-Paulet, A., Labenne, M., Colombani, M., Soichot, P., Huet, F., Hainque, B., Sternberg, D., Fontaine, B., Gouyon, J.-B., Thauvin-Robinet, C. <strong>Severe neonatal non-dystrophic myotonia secondary to a novel mutation of the voltage-gated sodium channel (SCN4A) gene.</strong> Am. J. Med. Genet. 146A: 380-383, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18203179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18203179</a>] [<a href="https://doi.org/10.1002/ajmg.a.32141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18203179">Gay et al. (2008)</a> identified a de novo heterozygous 3891C-A transversion in exon 21 of the SCN4A gene, resulting in an asn1297-to-lys (N1297K) substitution in the interdomain loop III-IV. The mutation was not found in either parent or in 100 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18203179" 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>.0028 PARAMYOTONIA CONGENITA</strong>
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SCN4A, ILE693THR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80338956 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338956;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=rs80338956" 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=rs80338956" 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=RCV000006286 OR RCV000020266 OR RCV000485864 OR RCV002267605" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006286, RCV000020266, RCV000485864, RCV002267605" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006286...</a>
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<p>In 6 patients from 4 unrelated European families with paramyotonia congenita (PMC; <a href="/entry/168300">168300</a>), <a href="#35" class="mim-tip-reference" title="Matthews, E., Guet, A., Mayer, M., Vicart, S., Pemble, S., Sternberg, D., Fontaine, B., Hanna, M. G. <strong>Neonatal hypotonia can be a sodium channelopathy: recognition of a new phenotype.</strong> Neurology 71: 1740-1742, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19015492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19015492</a>] [<a href="https://doi.org/10.1212/01.wnl.0000335269.21550.0e" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19015492">Matthews et al. (2008)</a> identified a heterozygous mutation in the SCN4A gene, resulting in an ile693-to-thr (I693T) substitution in the domain II S4-5 cytoplasmic loop. All the patients presented with transient neonatal hypotonia, in some cases requiring feeding or respiratory assistance, and later developed classic PMC by age 5 years. Earlier generations of 3 of the families reported a history of PMC without neonatal hypotonia. The findings expanded the phenotypic spectrum of PMC to include neonatal hypotonia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19015492" 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="0029" class="mim-anchor"></a>
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<strong>.0029 PARAMYOTONIA CONGENITA</strong>
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SCN4A, ILE141VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908561 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908561;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=rs121908561" 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=rs121908561" 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=RCV000006287" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006287" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006287</a>
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<p>In affected members of a family with a phenotype consistent with paramyotonia congenita (PMC; <a href="/entry/168300">168300</a>), <a href="#44" class="mim-tip-reference" title="Petitprez, S., Tiab, L., Chen, L., Kappeler, L., Rosler, K. M., Schorderet, D., Abriel, H., Burgunder, J.-M. <strong>A novel dominant mutation of the Na(v)1.4 alpha-subunit domain I leading to sodium channel myotonia.</strong> Neurology 71: 1669-1675, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19015483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19015483</a>] [<a href="https://doi.org/10.1212/01.wnl.0000335168.86248.55" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19015483">Petitprez et al. (2008)</a> identified a heterozygous A-to-G transition in exon 4 of the SCN4A gene, resulting in an ile141-to-val (I141V) substitution in the first transmembrane segment of domain I. The patients had myotonia without muscle weakness. The mutation was not identified in unaffected family members and 100 control individuals. In vitro functional expression studies showed that the mutant protein resulted in a hyperpolarizing shift of the activation curve, with concomitant increase in window current amplitude, suggestive of a gain of function. The studies also showed enhanced slow inactivation, which may have prevented weakness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19015483" 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="0030" class="mim-anchor"></a>
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<strong>.0030 HYPOKALEMIC PERIODIC PARALYSIS, TYPE 2</strong>
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SCN4A, ARG1132GLN
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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> rs80338789 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338789;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/rs80338789?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=rs80338789" 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=rs80338789" 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=RCV000043510 OR RCV000517960 OR RCV000692011 OR RCV001174896" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000043510, RCV000517960, RCV000692011, RCV001174896" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000043510...</a>
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<p>In affected members of a 3-generation family with hypokalemic periodic paralysis type 2 (HOKPP2; <a href="/entry/613345">613345</a>), <a href="#10" class="mim-tip-reference" title="Carle, T., Lhuillier, L., Luce, S., Sternberg, D., Devuyst, O., Fontaine, B., Tabti, N. <strong>Gating defects of a novel Na+ channel mutant causing hypokalemic periodic paralysis.</strong> Biochem. Biophys. Res. Commun. 348: 653-661, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16890191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16890191</a>] [<a href="https://doi.org/10.1016/j.bbrc.2006.07.101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16890191">Carle et al. (2006)</a> identified a heterozygous 3395G-A transition in exon 18 of the SCN4A gene, resulting in an arg1132-to-gln (R1132Q) substitution in the voltage sensor S4 of domain III. The mutation, which segregated with the disorder in the family, was not found in 325 control individuals. In vitro functional expression studies in HEK cells showed that the mutation induced a depolarizing shift in the voltage dependence, as well as enhancement of both fast and slow inactivation. These results were consistent with a loss-of-function effect with reduced effectiveness of membrane excitability, resulting in muscle hypoexcitability. Sodium channel conductance was similar to wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16890191" 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 Xenopus oocytes, <a href="#17" class="mim-tip-reference" title="Francis, D. G., Rybalchenko, V., Struyk, A., Cannon, S. C. <strong>Leaky sodium channels from voltage sensor mutations in periodic paralysis, but not paramyotonia.</strong> Neurology 76: 1635-1641, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21490317/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21490317</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21490317[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.0b013e318219fb57" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21490317">Francis et al. (2011)</a> demonstrated that the R1132Q mutation caused an abnormal gating pore current with a sustained inward sodium flow, consistent with a leaky channel. This current is sufficient to depolarize and render the muscle fiber inexcitable particularly during low external potassium. The findings suggested a mechanism for loss of sarcolemmal excitability during attacks of weakness in HOKPP. In contrast, the R1148C mutation (<a href="#0003">603967.0003</a>) causing paramyotonia congenita did not result in gating pore abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21490317" 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>.0031 MYASTHENIC SYNDROME, CONGENITAL, 16</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">rs80338951 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338951;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=rs80338951" 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=rs80338951" 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=RCV000020280 OR RCV000201211 OR RCV000235040" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000020280, RCV000201211, RCV000235040" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000020280...</a>
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<p>For discussion of the ser246-to-leu (S246L) mutation in the SCN4A gene that was found in compound heterozygous state in a patient with congenital myasthenic syndrome-16 (CMS16; <a href="/entry/614198">614198</a>) by <a href="#62" class="mim-tip-reference" title="Tsujino, A., Maertens, C., Ohno, K., Shen, X.-M., Fukuda, T., Harper, C. M., Cannon, S. C., Engel, A. G. <strong>Myasthenic syndrome caused by mutation of the SCN4A sodium channel.</strong> Proc. Nat. Acad. Sci. 100: 7377-7382, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12766226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12766226</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12766226[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.1230273100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12766226">Tsujino et al. (2003)</a>, see <a href="#0018">603967.0018</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12766226" 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>.0032 MYASTHENIC SYNDROME, CONGENITAL, 16</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> rs863225046 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs863225046;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/rs863225046?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=rs863225046" 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=rs863225046" 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=RCV000201212 OR RCV001209122" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000201212, RCV001209122" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000201212...</a>
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<p>In a 57-year-old woman, born of consanguineous parents, with congenital myasthenic syndrome-16 (CMS16; <a href="/entry/614198">614198</a>), <a href="#2" class="mim-tip-reference" title="Arnold, W. D., Feldman, D. H., Ramirez, S., He, L., Kassar, D., Quick, A., Klassen, T. L., Lara, M., Nguyen, J., Kissel, J. T., Lossin, C., Maselli, R. A. <strong>Defective fast inactivation recovery of Na(v)1.4 in congenital myasthenic syndrome.</strong> Ann. Neurol. 77: 840-850, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25707578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25707578</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25707578[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/10.1002/ana.24389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25707578">Arnold et al. (2015)</a> identified a homozygous c.4370G-A transition (c.4370G-A, NM_000334.4) in exon 24 of the SCN4A gene, resulting in an arg1457-to-his (R1457H) substitution at a conserved residue in the voltage-sensing D4/S4 transmembrane domain. In vitro electrophysiologic studies showed that the mutation caused a 25-mV hyperpolarizing shift in the voltage dependence of inactivation, resulting in enhanced fast inactivation as well as slowed recovery from fast inactivation. In addition, repetitive stimuli elicited markedly weaker current responses. These changes resulted in reduced channel availability, which could explain the patient's muscle weakness. The unaffected parents and sibs were heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25707578" 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>.0033 VARIANT OF UNKNOWN SIGNIFICANCE</strong>
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SCN4A, GLY1537SER (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs571210585;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs571210585</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> rs571210585 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs571210585;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/rs571210585?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=rs571210585" 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=rs571210585" 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=RCV000207488 OR RCV000551049 OR RCV004530250 OR RCV005003560" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000207488, RCV000551049, RCV004530250, RCV005003560" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000207488...</a>
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<p>This variant is classified as a variant of unknown significance because its contribution to essential tremor (see, e.g., ETM1, <a href="/entry/190300">190300</a>) has not been confirmed.</p><p>In 5 individuals from a Spanish family with variable manifestations of essential tremor, <a href="#5" class="mim-tip-reference" title="Bergareche, A., Bednarz, M. Sanchez, E., Krebs, C. E., Ruiz-Martinez, J., De La Riva, P., Makarov, V., Gorostidi, A., Jurkat-Rott, K., Marti-Masso, J. F., Paisan-Ruiz, C. <strong>SCN4A pore mutation pathogenetically contributes to autosomal dominant essential tremor and may increase susceptibility to epilepsy.</strong> Hum. Molec. Genet. 24: 7111-7120, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26427606/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26427606</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26427606[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddv410" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26427606">Bergareche et al. (2015)</a> identified a heterozygous c.4609G-A transition in the SCN4A gene, resulting in a gly1537-to-ser (G1537S) substitution at a highly conserved residue in the portion of the IVS5-S6 loop that dips into the membrane and forms the lining of the pore, which is important for ion selectivity. The variant, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the phenotype and was not found in the dbSNP (build 137), 1000 Genomes Project, or Exome Variant Server databases, or in 188 ethnically matched control chromosomes. The authors noted that the variant was subsequently listed in the dbSNP database as <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs571210585;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs571210585</a> and at a low frequency (6.6 x 10(-5)) in the ExAC database. Whole-cell patch-clamp studies indicated that the variant channel had a tendency toward faster activation and significantly faster inactivation at near-threshold potentials compared to wildtype, which may gradually decrease the amplitude in repetitive action potential firing and facilitate oscillations associated with tremor. Monovalent ion selectivity studies showed that the variant channel had increased conductivity for ammonium and potassium, consistent with a gain of function. The phenotype in this family was heterogeneous: the age at onset of postural and/or action tremor ranged from the early twenties to early sixties. Two patients had tremor occurring in the hands and head, 2 had tremor of both hands, which progressed to head tremor in 1 patient and voice tremor in the other, and 1 patient showed only head tremor. In addition, 2 patients had generalized epilepsy with onset at ages 10 and 20 years, respectively. <a href="#5" class="mim-tip-reference" title="Bergareche, A., Bednarz, M. Sanchez, E., Krebs, C. E., Ruiz-Martinez, J., De La Riva, P., Makarov, V., Gorostidi, A., Jurkat-Rott, K., Marti-Masso, J. F., Paisan-Ruiz, C. <strong>SCN4A pore mutation pathogenetically contributes to autosomal dominant essential tremor and may increase susceptibility to epilepsy.</strong> Hum. Molec. Genet. 24: 7111-7120, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26427606/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26427606</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26427606[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddv410" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26427606">Bergareche et al. (2015)</a> concluded that the SCN4A variant contributed to tremor and increased the susceptibility to epilepsy in this family, and that essential tremor may result from a channelopathy in some cases. The G1537S variant was not detected in 76 sporadic and 25 familial Spanish patients with essential tremor, and other pathogenic SCN4A variants were not found in 22 additional cases with familial essential tremor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26427606" 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>.0034 CONGENITAL MYOPATHY 22A, CLASSIC</strong>
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PARAMYOTONIA CONGENITA, INCLUDED
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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> rs764718003 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs764718003;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/rs764718003?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=rs764718003" 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=rs764718003" 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=RCV001808030 OR RCV002267640 OR RCV002464491 OR RCV003227994 OR RCV003227995 OR RCV005023264" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001808030, RCV002267640, RCV002464491, RCV003227994, RCV003227995, RCV005023264" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001808030...</a>
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<p>In a 35-year-old Caucasian woman, born of unrelated parents (family 2), with classic congenital myopathy-22A (CMYO22A; <a href="/entry/620351">620351</a>), <a href="#69" class="mim-tip-reference" title="Zaharieva, I. T., Thor, M. G., Oates, E. C., van Karnebeek, C., Hendson, G., Blom, E., Witting, N., Rasmussen, M., Gabbett, M. T., Ravenscroft, G., Sframeli, M., Suetterlin, K., and 28 others. <strong>Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy.</strong> Brain 139: 674-691, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26700687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26700687</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26700687[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/awv352" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26700687">Zaharieva et al. (2016)</a> identified compound heterozygous mutations in the SCN4A gene: a c.673C-T transition, resulting in an arg225-to-trp (R225W) substitution, and a c.3628G-T transversion, resulting in a cys1209-to-phe (C1209F; <a href="#0035">603967.0035</a>) substitution. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Neither variant was present in the ExAC database. Electrophysiologic studies in HEK293 cells transfected with the mutations showed that R225W was a hypomorphic allele causing reduced current amplitude, whereas C1209F resulted in a complete loss of channel function. The patient showed moderate hypotonia at birth requiring early respiratory support, delayed motor milestones, and proximal muscle weakness, but she did not have limb contractures and was ambulatory with a slow waddling gait. Her motor skills improved during childhood, but began to deteriorate around age 30. Her carrier parents were clinically unaffected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26700687" 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="#69" class="mim-tip-reference" title="Zaharieva, I. T., Thor, M. G., Oates, E. C., van Karnebeek, C., Hendson, G., Blom, E., Witting, N., Rasmussen, M., Gabbett, M. T., Ravenscroft, G., Sframeli, M., Suetterlin, K., and 28 others. <strong>Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy.</strong> Brain 139: 674-691, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26700687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26700687</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26700687[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/awv352" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26700687">Zaharieva et al. (2016)</a> noted that <a href="#33" class="mim-tip-reference" title="Lee, S. C., Kim, H. S., Park, Y. E., Choi, Y. C., Park, K. H., Kim, D. S. <strong>Clinical diversity of SCN4A-mutation-associated skeletal muscle sodium channelopathy.</strong> J. Clin. Neurol. 5: 186-191, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20076800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20076800</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20076800[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/10.3988/jcn.2009.5.4.186" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20076800">Lee et al. (2009)</a> had identified a heterozygous R225W mutation in a 21-year-old Korean man (patient 3) with mild nonpainful paramyotonia congenita (PMC; <a href="/entry/168300">168300</a>). R225W is located at the cytoplasmic side of transmembrane S3 segment of domain I. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20076800+26700687" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV003227546" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003227546" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003227546</a>
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<p>For discussion of the c.3628G-T transversion in the SCN4A gene, resulting in a cys1209-to-phe (C1209F) substitution, that was found in compound heterozygous state in a patient with classic congenital myopathy-22A (CMYO22A; <a href="/entry/620351">620351</a>), by <a href="#69" class="mim-tip-reference" title="Zaharieva, I. T., Thor, M. G., Oates, E. C., van Karnebeek, C., Hendson, G., Blom, E., Witting, N., Rasmussen, M., Gabbett, M. T., Ravenscroft, G., Sframeli, M., Suetterlin, K., and 28 others. <strong>Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy.</strong> Brain 139: 674-691, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26700687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26700687</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26700687[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/awv352" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26700687">Zaharieva et al. (2016)</a>, see <a href="#0034">603967.0034</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26700687" 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>.0036 CONGENITAL MYOPATHY 22B, SEVERE FETAL</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV003227547" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003227547" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003227547</a>
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<p>In 3 affected sibs from a consanguineous Sudanese family (family 5) with severe fetal congenital myopathy-22B (CMYO22B; <a href="/entry/620369">620369</a>), <a href="#69" class="mim-tip-reference" title="Zaharieva, I. T., Thor, M. G., Oates, E. C., van Karnebeek, C., Hendson, G., Blom, E., Witting, N., Rasmussen, M., Gabbett, M. T., Ravenscroft, G., Sframeli, M., Suetterlin, K., and 28 others. <strong>Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy.</strong> Brain 139: 674-691, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26700687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26700687</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26700687[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/awv352" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26700687">Zaharieva et al. (2016)</a> identified a homozygous c.1144C-A transversion in the SCN4A gene, resulting in a pro382-to-thr (P382T) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The mutation was not present in the ExAC database. Electrophysiologic studies in HEK293 cells transfected with the mutation showed that it resulted in a complete loss of channel function. All 3 patients died prior to delivery or shortly after birth. They had contractures, muscle hypoplasia, and hydrops with pulmonary hypoplasia. The carrier parents were clinically unaffected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26700687" 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> rs933258893 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs933258893;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/rs933258893?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=rs933258893" 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=rs933258893" 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=RCV001387955 OR RCV003227973" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001387955, RCV003227973" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001387955...</a>
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<p>In 3 sibs, born of unrelated Australian parents (family 6), with severe fetal congenital myopathy-22B (CMYO22B; <a href="/entry/620369">620369</a>), <a href="#69" class="mim-tip-reference" title="Zaharieva, I. T., Thor, M. G., Oates, E. C., van Karnebeek, C., Hendson, G., Blom, E., Witting, N., Rasmussen, M., Gabbett, M. T., Ravenscroft, G., Sframeli, M., Suetterlin, K., and 28 others. <strong>Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy.</strong> Brain 139: 674-691, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26700687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26700687</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26700687[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/awv352" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26700687">Zaharieva et al. (2016)</a> identified compound heterozygous mutations in the SCN4A gene: a c.608T-A transversion, resulting in a met203-to-lys (M203K) substitution, and a c.4779C-A transversion, resulting in a tyr1593-to-ter (Y1593X; <a href="#0038">603967.0038</a>) substitution. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Neither mutation was present in the ExAC database. Electrophysiologic studies in HEK293 cells transfected with the M203K mutation showed that it was a hypomorphic allele causing reduced current amplitude; the voltage dependence of activation and fast inactivation was shifted in the depolarizing direction. The Y1593X nonsense mutation was predicted to cause nonsense-mediated mRNA decay and a complete loss of channel function. All patients died in utero or shortly after birth. They had muscle hypoplasia, contractures, and hydrops with pulmonary hypoplasia. The carrier parents were clinically unaffected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26700687" 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>.0038 CONGENITAL MYOPATHY 22B, SEVERE FETAL</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV003227549" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003227549" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003227549</a>
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<p>For discussion of the c.4779C-A transversion in the SCN4A gene, resulting in a tyr1593-to-ter (Y1593X) substitution, that was found in compound heterozygous state in 3 sibs with severe fetal congenital myopathy-22B (CMYO22B; <a href="/entry/620369">620369</a>) by <a href="#69" class="mim-tip-reference" title="Zaharieva, I. T., Thor, M. G., Oates, E. C., van Karnebeek, C., Hendson, G., Blom, E., Witting, N., Rasmussen, M., Gabbett, M. T., Ravenscroft, G., Sframeli, M., Suetterlin, K., and 28 others. <strong>Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy.</strong> Brain 139: 674-691, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26700687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26700687</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26700687[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/awv352" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26700687">Zaharieva et al. (2016)</a>, see <a href="#0037">603967.0037</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26700687" 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>.0039 CONGENITAL MYOPATHY 22A, CLASSIC</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV003227550" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003227550" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003227550</a>
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<p>In 2 brothers, born of unrelated parents of East Indian descent, with classic congenital myopathy-22A (CMYO22A; <a href="/entry/620351">620351</a>), <a href="#22" class="mim-tip-reference" title="Gonorazky, H. D., Marshall, C. R., Al-Murshed, M., Hazrati, L. N., Thor, M. G., Hanna, M. G., Mannikko, R., Ray, P. N., Yoon, G. <strong>Congenital myopathy with "corona" fibres, selective muscle atrophy, and craniosynostosis associated with novel recessive mutations in SCN4A.</strong> Neuromusc. Disord. 27: 574-580, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28262468/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28262468</a>] [<a href="https://doi.org/10.1016/j.nmd.2017.02.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28262468">Gonorazky et al. (2017)</a> identified compound heterozygous missense mutations in the SCN4A gene: a c.1123T-C transition (c.1123T-C, NM_000334.4), resulting in a cys375-to-arg (C375R) substitution, and a c.3425G-A transition, resulting in an arg1142-to-gln (R1142Q; <a href="#0040">603967.0040</a>) substitution. The mutations, which were found by exome sequencing, segregated with the disorder in the family. In vitro electrophysiologic studies in HEK293 cells showed that the C375R mutation abolished sodium activity and caused a complete loss of SCN4A function, whereas the R1142Q mutation was hypomorphic with reduced peak current densities due to a 4-mV depolarizing shift of activation. Fast inactivation properties of the R1142Q mutant channel were also mildly affected. The patients, who were 21 and 18 years of age, showed hypotonia at birth, proximal muscle weakness of the upper and lower limbs, difficulty walking, and facial muscle weakness. Both also had scaphocephaly due to synostosis of the sagittal and metopic sutures. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28262468" 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> rs780703403 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs780703403;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/rs780703403?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=rs780703403" 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=rs780703403" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the c.3425G-A transition (c.3425G-A, NM_000334.4) in the SCN4A gene, resulting in an arg1142-to-gln (R1142Q) substitution, that was found in compound heterozygous state in 2 sibs with classic congenital myopathy-22A (CMYO22A; <a href="/entry/620351">620351</a>) by <a href="#22" class="mim-tip-reference" title="Gonorazky, H. D., Marshall, C. R., Al-Murshed, M., Hazrati, L. N., Thor, M. G., Hanna, M. G., Mannikko, R., Ray, P. N., Yoon, G. <strong>Congenital myopathy with "corona" fibres, selective muscle atrophy, and craniosynostosis associated with novel recessive mutations in SCN4A.</strong> Neuromusc. Disord. 27: 574-580, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28262468/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28262468</a>] [<a href="https://doi.org/10.1016/j.nmd.2017.02.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28262468">Gonorazky et al. (2017)</a>, see <a href="#0039">603967.0039</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28262468" 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> rs879253789 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs879253789;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/rs879253789?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=rs879253789" 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=rs879253789" 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=RCV000235032 OR RCV001056500 OR RCV002512068 OR RCV003227471" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000235032, RCV001056500, RCV002512068, RCV003227471" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000235032...</a>
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<p><strong><em>Congenital Myasthenic Syndrome 16</em></strong></p><p>
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In a 26-year-old Lebanese woman, born of consanguineous parents, with congenital myasthenic syndrome-16 (CMS16; <a href="/entry/614198">614198</a>), <a href="#23" class="mim-tip-reference" title="Habbout, K., Poulin, H., Rivier, F., Giuliano, S., Sternberg, D., Fontaine, B., Eymard, B., Morales, R. J., Echenne, B., King, L., Hanna, M. G., Mannikko, R., Chahine, M., Nicole, S., Bendahhou, S. <strong>A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with periodic paralysis.</strong> Neurology 86: 161-169, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26659129/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26659129</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26659129[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.0000000000002264" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26659129">Habbout et al. (2016)</a> identified a homozygous c.4360C-T transition (c.4360C-T, NM_000334.4) in exon 24 of the SCN4A gene, resulting in an arg1454-to-trp (R1454W) substitution in the DIVS4 domain. Each unaffected parent was heterozygous for the mutation. In vitro functional expression studies showed that the mutation resulted in a loss-of-function effect, with slowed current decay, slowed fast inactivation, and increased activation time compared to wildtype. Slowed inactivation was also disturbed. Current density was not affected, but there was a decrease in current amplitude in response to repetitive stimulation above 10 Hz. The findings thus showed a combination of gating behaviors that favor the inactivation state; defective inactivation may induce fatigable weakness during muscle firing. The phenotype in this patient comprised both CMS and normokalemic periodic paralysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26659129" 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>Classic Congenital Myopathy 22A</em></strong></p><p>
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For discussion of the c.4360C-T transition in the SCN4A gene, resulting in an R1454W mutation, that was found in compound heterozygous state in a patient with classic congenital myopathy-22A (CMYO22A; <a href="/entry/620351">620351</a>) by <a href="#6" class="mim-tip-reference" title="Berghold, V. M., Koko, M., Berutti, R., Plecko, B. <strong>Novel SCN4A variant associated with a severe congenital myasthenic syndrome/myopathy phenotype.</strong> Front. Pediat. 10: 944784, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36090556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36090556</a>] [<a href="https://doi.org/10.3389/fped.2022.944784" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36090556">Berghold et al. (2022)</a>, see <a href="#0042">603967.0042</a>. <a href="#6" class="mim-tip-reference" title="Berghold, V. M., Koko, M., Berutti, R., Plecko, B. <strong>Novel SCN4A variant associated with a severe congenital myasthenic syndrome/myopathy phenotype.</strong> Front. Pediat. 10: 944784, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36090556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36090556</a>] [<a href="https://doi.org/10.3389/fped.2022.944784" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36090556">Berghold et al. (2022)</a> noted that the R1454W variant was present at a low frequency (1.6 x 10(-5)) in heterozygous state in the gnomAD database. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36090556" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001065707 OR RCV002512136 OR RCV003227512 OR RCV004792710" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001065707, RCV002512136, RCV003227512, RCV004792710" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001065707...</a>
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<p>In an 18-year-old girl, born of unrelated parents, with classic congenital myopathy-22A (CMYO22A; <a href="/entry/620351">620351</a>), <a href="#6" class="mim-tip-reference" title="Berghold, V. M., Koko, M., Berutti, R., Plecko, B. <strong>Novel SCN4A variant associated with a severe congenital myasthenic syndrome/myopathy phenotype.</strong> Front. Pediat. 10: 944784, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36090556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36090556</a>] [<a href="https://doi.org/10.3389/fped.2022.944784" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36090556">Berghold et al. (2022)</a> identified compound heterozygous missense mutations in the SCN4A gene: a c.3615C-G transversion (c.3615C-G, NM_000334.4), resulting in an asn1205-to-lys (N1205K) substitution at a conserved region in domain III, and R1454W (<a href="#0041">603967.0041</a>). The mutations, which were found by whole-exome sequencing, were inherited from the unaffected parents. R1454W, located in the voltage sensor of domain IV, had been demonstrated to be a loss-of-function variant by <a href="#23" class="mim-tip-reference" title="Habbout, K., Poulin, H., Rivier, F., Giuliano, S., Sternberg, D., Fontaine, B., Eymard, B., Morales, R. J., Echenne, B., King, L., Hanna, M. G., Mannikko, R., Chahine, M., Nicole, S., Bendahhou, S. <strong>A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with periodic paralysis.</strong> Neurology 86: 161-169, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26659129/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26659129</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26659129[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.0000000000002264" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26659129">Habbout et al. (2016)</a>. N1205K, located in a region forming the channel pore, was a novel variant. It was not present in the gnomAD database. Functional studies of N1205K were not performed, but it was predicted to cause a loss of function based on studies of paralogous variants in other SCNA genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=26659129+36090556" 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>Ion channels--basic science and clinical disease.</strong>
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New Eng. J. Med. 336: 1575-1586, 1997. Note: Erratum: New Eng. J. Med. 337: 579 only, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9164815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9164815</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9164815" 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/10.1056/NEJM199705293362207" target="_blank">Full Text</a>]
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Arnold, W. D., Feldman, D. H., Ramirez, S., He, L., Kassar, D., Quick, A., Klassen, T. L., Lara, M., Nguyen, J., Kissel, J. T., Lossin, C., Maselli, R. A.
|
|
<strong>Defective fast inactivation recovery of Na(v)1.4 in congenital myasthenic syndrome.</strong>
|
|
Ann. Neurol. 77: 840-850, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25707578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25707578</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25707578[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=25707578" 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/ana.24389" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Bendahhou2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bendahhou, S., Cummins, T. R., Griggs, R. C., Fu, Y.-H., Ptacek, L. J.
|
|
<strong>Sodium channel inactivation defects are associated with acetazolamide-exacerbated hypokalemic periodic paralysis.</strong>
|
|
Ann. Neurol. 50: 417-420, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11558801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11558801</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11558801" 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/ana.1144" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Bennani-Baiti1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bennani-Baiti, I. M., Jones, B. K., Liebhaber, S. A., Cooke, N. E.
|
|
<strong>Physical linkage of the human growth hormone gene cluster and the skeletal muscle sodium channel alpha-subunit gene (SCN4A) on chromosome 17.</strong>
|
|
Genomics 29: 647-652, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8575757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8575757</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8575757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1995.9954" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Bergareche2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bergareche, A., Bednarz, M. Sanchez, E., Krebs, C. E., Ruiz-Martinez, J., De La Riva, P., Makarov, V., Gorostidi, A., Jurkat-Rott, K., Marti-Masso, J. F., Paisan-Ruiz, C.
|
|
<strong>SCN4A pore mutation pathogenetically contributes to autosomal dominant essential tremor and may increase susceptibility to epilepsy.</strong>
|
|
Hum. Molec. Genet. 24: 7111-7120, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26427606/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26427606</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26427606[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=26427606" 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/ddv410" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Berghold2022" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Berghold, V. M., Koko, M., Berutti, R., Plecko, B.
|
|
<strong>Novel SCN4A variant associated with a severe congenital myasthenic syndrome/myopathy phenotype.</strong>
|
|
Front. Pediat. 10: 944784, 2022.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36090556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36090556</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36090556" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.3389/fped.2022.944784" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Brancati2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brancati, F., Valente, E. M., Davies, N. P., Sarkozy, A., Sweeney, M. G., LoMonaco, M., Pizzuti, A., Hanna, M. G., Dallapiccola, B.
|
|
<strong>Severe infantile hyperkalaemic periodic paralysis and paramyotonia congenita: broadening the clinical spectrum associated with the T704M mutation in SCN4A.</strong>
|
|
J. Neurol. Neurosurg. Psychiat. 74: 1339-1341, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12933953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12933953</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12933953" 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/jnnp.74.9.1339" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Bulman1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bulman, D. E., Scoggan, K. A., van Oene, M. D., Nicolle, M. W., Hahn, A. F., Tollar, L. L., Ebers, G. C.
|
|
<strong>A novel sodium channel mutation in a family with hypokalemic periodic paralysis.</strong>
|
|
Neurology 53: 1932-1936, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10599760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10599760</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10599760" 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.53.9.1932" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Cannon2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cannon, S. C.
|
|
<strong>When all is lost...a severe myopathy with hypotonia from sodium channel mutations.</strong>
|
|
Brain 139: 642-644, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26917582/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26917582</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26917582" 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/awv400" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Carle2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Carle, T., Lhuillier, L., Luce, S., Sternberg, D., Devuyst, O., Fontaine, B., Tabti, N.
|
|
<strong>Gating defects of a novel Na+ channel mutant causing hypokalemic periodic paralysis.</strong>
|
|
Biochem. Biophys. Res. Commun. 348: 653-661, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16890191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16890191</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16890191" 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.bbrc.2006.07.101" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Colding-Jorgensen2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Colding-Jorgensen, E., Duno, M., Vissing, J.
|
|
<strong>Autosomal dominant monosymptomatic myotonia permanens.</strong>
|
|
Neurology 67: 153-155, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16832098/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16832098</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16832098" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000223838.88872.da" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Davies2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Davies, N. P., Eunson, L. H., Gregory, R. P., Mills, K. R., Morrison, P. J., Hanna, M. G.
|
|
<strong>Clinical, electrophysiological, and molecular genetic studies in a new family with paramyotonia congenita.</strong>
|
|
J. Neurol. Neurosurg. Psychiat. 68: 504-507, 2000. Note: Erratum: J. Neurol. Neurosurg. Psychiat. 69: 139 only, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10727489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10727489</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10727489" 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/jnnp.68.4.504" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Davies2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Davies, N. P., Eunson, L. H., Samuel, M., Hanna, M. G.
|
|
<strong>Sodium channel gene mutations in hypokalemic periodic paralysis: an uncommon cause in the UK.</strong>
|
|
Neurology 57: 1323-1325, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11591859/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11591859</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11591859" 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.57.7.1323" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" 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="15" class="mim-anchor"></a>
|
|
<a id="Feero1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Feero, W. G., Wang, J., Barany, F., Zhou, J., Todorovic, S. M., Conwit, R., Galloway, G., Hausmanowa-Petrusewicz, I., Fidzianska, A., Arahata, K., Wessel, H. B., Wadelius, C., Marks, H. G., Hartlage, P., Hayakawa, H., Hoffman, E. P.
|
|
<strong>Hyperkalemic periodic paralysis: rapid molecular diagnosis and relationship of genotype to phenotype in 12 families.</strong>
|
|
Neurology 43: 668-673, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8385748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8385748</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8385748" 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.43.4.668" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Fontaine1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fontaine, B., Khurana, T. S., Hoffman, E. P., Bruns, G. A. P., Haines, J. L., Trofatter, J. A., Hanson, M. P., Rich, J., McFarlane, H., Yasek, D. M., Romano, D., Gusella, J. F., Brown, R. H., Jr.
|
|
<strong>Hyperkalemic periodic paralysis and the adult muscle sodium channel alpha-subunit gene.</strong>
|
|
Science 250: 1000-1002, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2173143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2173143</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2173143" 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.2173143" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Francis2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Francis, D. G., Rybalchenko, V., Struyk, A., Cannon, S. C.
|
|
<strong>Leaky sodium channels from voltage sensor mutations in periodic paralysis, but not paramyotonia.</strong>
|
|
Neurology 76: 1635-1641, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21490317/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21490317</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21490317[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=21490317" 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.0b013e318219fb57" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Gay2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gay, S., Dupuis, D., Faivre, L., Masurel-Paulet, A., Labenne, M., Colombani, M., Soichot, P., Huet, F., Hainque, B., Sternberg, D., Fontaine, B., Gouyon, J.-B., Thauvin-Robinet, C.
|
|
<strong>Severe neonatal non-dystrophic myotonia secondary to a novel mutation of the voltage-gated sodium channel (SCN4A) gene.</strong>
|
|
Am. J. Med. Genet. 146A: 380-383, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18203179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18203179</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18203179" 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/ajmg.a.32141" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="George1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
George, A. L., Jr., Iyer, G. S., Kleinfield, R., Kallen, R. G., Barchi, R. L.
|
|
<strong>Genomic organization of the human skeletal muscle sodium channel gene.</strong>
|
|
Genomics 15: 598-606, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8385647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8385647</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8385647" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1993.1113" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="George1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
George, A. L., Jr., Komisarof, J., Kallen, R. G., Barchi, R. L.
|
|
<strong>Primary structure of the adult human skeletal muscle voltage-dependent sodium channel.</strong>
|
|
Ann. Neurol. 31: 131-137, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1315496/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1315496</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1315496" 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/ana.410310203" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="George1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
George, A. L., Jr., Ledbetter, D. H., Kallen, R. G., Barchi, R. L.
|
|
<strong>Assignment of a human skeletal muscle sodium channel alpha-subunit gene (SCN4A) to 17q23.1-25.3.</strong>
|
|
Genomics 9: 555-556, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1851726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1851726</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1851726" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(91)90425-e" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Gonorazky2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gonorazky, H. D., Marshall, C. R., Al-Murshed, M., Hazrati, L. N., Thor, M. G., Hanna, M. G., Mannikko, R., Ray, P. N., Yoon, G.
|
|
<strong>Congenital myopathy with "corona" fibres, selective muscle atrophy, and craniosynostosis associated with novel recessive mutations in SCN4A.</strong>
|
|
Neuromusc. Disord. 27: 574-580, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28262468/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28262468</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28262468" 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.2017.02.001" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Habbout2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Habbout, K., Poulin, H., Rivier, F., Giuliano, S., Sternberg, D., Fontaine, B., Eymard, B., Morales, R. J., Echenne, B., King, L., Hanna, M. G., Mannikko, R., Chahine, M., Nicole, S., Bendahhou, S.
|
|
<strong>A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with periodic paralysis.</strong>
|
|
Neurology 86: 161-169, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26659129/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26659129</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26659129[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=26659129" 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.0000000000002264" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Hayward2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hayward, L. J., Kim, J. S., Lee, M.-Y., Zhou, H., Kim, J. W., Misra, K., Salajegheh, M., Wu, F., Matsuda, C., Reid, V., Cros, D., Hoffman, E. P., Renaud, J.-M., Cannon, S. C., Brown, R. H., Jr.
|
|
<strong>Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and potassium-sensitive weakness.</strong>
|
|
J. Clin. Invest. 118: 1437-1449, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18317596/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18317596</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18317596[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=18317596" 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/JCI32638" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Heine1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Heine, R., Pika, U., Lehmann-Horn, F.
|
|
<strong>A novel SCN4A mutation causing myotonia aggravated by cold and potassium.</strong>
|
|
Hum. Molec. Genet. 2: 1349-1353, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8242056/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8242056</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8242056" 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/2.9.1349" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Hisama2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hisama, F. M.
|
|
<strong>Familial periodic paralysis and Charcot-Marie-Tooth disease in a 7-generation family.</strong>
|
|
Arch. Neurol. 62: 135-138, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15642860/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15642860</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15642860" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archneur.62.1.135" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Iaizzo1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Iaizzo, P. A., Franke, C., Hatt, H., Spittelmeister, W., Ricker, K., Rudel, R., Lehmann-Horn, F.
|
|
<strong>Altered sodium channel behaviour causes myotonia in autosomal dominantly inherited myotonia congenita.</strong>
|
|
Neuromusc. Disord. 1: 47-53, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1668369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1668369</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1668369" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0960-8966(91)90042-q" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Jurkat-Rott2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jurkat-Rott, K., Mitrovic, N., Hang, C., Kouzmekine, A., Iaizzo, P., Herzog, J., Lerche, H., Nicole, S., Vale-Santos, J., Chauveau, D., Fontaine, B., Lehmann-Horn, F.
|
|
<strong>Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current.</strong>
|
|
Proc. Nat. Acad. Sci. 97: 9549-9554, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10944223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10944223</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10944223[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=10944223" 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.97.17.9549" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Kelly1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kelly, P., Yang, W. S., Costigan, D., Farrell, M. A., Murphy, S., Hardiman, O.
|
|
<strong>Paramyotonia congenita and hyperkalemic periodic paralysis associated with a met1592-to-val substitution in the skeletal muscle sodium channel alpha subunit--a large kindred with a novel phenotype.</strong>
|
|
Neuromusc. Disord. 7: 105-111, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9131651/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9131651</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9131651" 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/s0960-8966(96)00429-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Kim2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kim, J., Hahn, Y., Sohn, E. H., Lee, Y. J., Yun, J. H., Kim, J. M., Chung, J. H.
|
|
<strong>Phenotypic variation of a thr704met mutation in skeletal sodium channel gene in a family with paralysis periodica paramyotonica.</strong>
|
|
J. Neurol. Neurosurg. Psychiat. 70: 618-623, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11309455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11309455</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11309455" 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/jnnp.70.5.618" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Koch1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Koch, M. C., Baumbach, K., George, A. L., Ricker, K.
|
|
<strong>Paramyotonia congenita without paralysis on exposure to cold: a novel mutation in the SCN4A gene (val1293ile).</strong>
|
|
Neuroreport 6: 2001-2004, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8580427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8580427</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8580427" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/00001756-199510010-00012" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Kuzmenkin2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kuzmenkin, A., Muncan, V., Jurkat-Rott, K., Hang, C., Lerche, H., Lehmann-Horn, F., Mitrovic, N.
|
|
<strong>Enhanced inactivation and pH sensitivity of Na+ channel mutations causing hypokalemic periodic paralysis type II.</strong>
|
|
Brain 125: 835-843, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11912116/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11912116</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11912116" 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/awf071" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Lee2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lee, S. C., Kim, H. S., Park, Y. E., Choi, Y. C., Park, K. H., Kim, D. S.
|
|
<strong>Clinical diversity of SCN4A-mutation-associated skeletal muscle sodium channelopathy.</strong>
|
|
J. Clin. Neurol. 5: 186-191, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20076800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20076800</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20076800[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=20076800" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.3988/jcn.2009.5.4.186" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Lerche1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lerche, H., Heine, R., Pika, U., George, A. L., Jr., Mitrovic, N., Browatzki, M., Weiss, T., Rivet-Bastide, M., Franke, C., Lomonaco, M., Ricker, K., Lehmann-Horn, F.
|
|
<strong>Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III-IV linker.</strong>
|
|
J. Physiol. 470: 13-22, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8308722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8308722</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8308722" 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.1993.sp019843" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Matthews2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matthews, E., Guet, A., Mayer, M., Vicart, S., Pemble, S., Sternberg, D., Fontaine, B., Hanna, M. G.
|
|
<strong>Neonatal hypotonia can be a sodium channelopathy: recognition of a new phenotype.</strong>
|
|
Neurology 71: 1740-1742, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19015492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19015492</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19015492" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000335269.21550.0e" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Matthews2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matthews, E., Labrum, R., Sweeney, M. G., Sud, R., Haworth, A., Chinnery, P. F., Meola, G., Schorge, S., Kullmann, D. M., Davis, M. B., Hanna, M. G.
|
|
<strong>Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis.</strong>
|
|
Neurology 72: 1544-1547, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19118277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19118277</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19118277[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=19118277" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000342387.65477.46" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Matthews2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matthews, E., Manzur, A. Y., Sud, R., Muntoni, F., Hanna, M. G.
|
|
<strong>Stridor as a neonatal presentation of skeletal muscle sodium channelopathy.</strong>
|
|
Arch. Neurol. 68: 127-129, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21220685/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21220685</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21220685" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archneurol.2010.347" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="McClatchey1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McClatchey, A. I., Lin, C. S., Wang, J., Hoffman, E. P., Rojas, C., Gusella, J. F.
|
|
<strong>The genomic structure of the human skeletal muscle sodium channel gene.</strong>
|
|
Hum. Molec. Genet. 1: 521-527, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1339144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1339144</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1339144" 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/1.7.521" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="McClatchey1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McClatchey, A. I., McKenna-Yasek, D., Cros, D., Worthen, H. G., Kuncl, R. W., DeSilva, S. M., Cornblath, D. R., Gusella, J. F., Brown, R. H., Jr.
|
|
<strong>Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel.</strong>
|
|
Nature Genet. 2: 148-152, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1338909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1338909</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1338909" 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/ng1092-148" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="McClatchey1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McClatchey, A. I., Van den Bergh, P., Pericak-Vance, M. A., Raskind, W., Verellen, C., McKenna-Yasek, D., Rao, K., Haines, J. L., Bird, T., Brown, R. H., Jr., Gusella, J. F.
|
|
<strong>Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita.</strong>
|
|
Cell 68: 769-774, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1310898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1310898</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1310898" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0092-8674(92)90151-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Meyer-Kleine1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meyer-Kleine, C., Otto, M., Zoll, B., Koch, M. C.
|
|
<strong>Molecular and genetic characterization of German families with paramyotonia congenita and demonstration of founder effect in the Ravensberg families.</strong>
|
|
Hum. Genet. 93: 707-710, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8005599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8005599</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8005599" 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/BF00201577" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Miller2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Miller, T. M., Dias da Silva, M. R., Miller, H. A., Kwiecinski, H., Mendell, J. R., Tawil, R., McManis, P., Griggs, R. C., Angelini, C., Servidei, S., Petajan, J., Dalakas, M. C., Ranum, L. P. W., Fu, Y. H., Ptacek, L. J.
|
|
<strong>Correlating phenotype and genotype in the periodic paralyses.</strong>
|
|
Neurology 63: 1647-1655, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15534250/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15534250</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15534250" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000143383.91137.00" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Orrell1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Orrell, R. W., Jurkat-Rott, K., Lehmann-Horn, F., Lane, R. J. M.
|
|
<strong>Familial cramp due to potassium-aggravated myotonia.</strong>
|
|
J. Neurol. Neurosurg. Psychiat. 65: 569-572, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9771789/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9771789</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9771789" 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/jnnp.65.4.569" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Petitprez2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Petitprez, S., Tiab, L., Chen, L., Kappeler, L., Rosler, K. M., Schorderet, D., Abriel, H., Burgunder, J.-M.
|
|
<strong>A novel dominant mutation of the Na(v)1.4 alpha-subunit domain I leading to sodium channel myotonia.</strong>
|
|
Neurology 71: 1669-1675, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19015483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19015483</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19015483" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000335168.86248.55" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Ptacek1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ptacek, L. J., George, A. L., Jr., Barchi, R. L., Griggs, R. C., Riggs, J. E., Robertson, M., Leppert, M. F.
|
|
<strong>Mutations in an S4 segment of the adult skeletal muscle sodium channel cause paramyotonia congenita.</strong>
|
|
Neuron 8: 891-897, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1316765/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1316765</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1316765" 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(92)90203-p" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Ptacek1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ptacek, L. J., George, A. L., Jr., Griggs, R. C., Tawil, R., Kallen, R. G., Barchi, R. L., Robertson, M., Leppert, M. F.
|
|
<strong>Identification of a mutation in the gene causing hyperkalemic periodic paralysis.</strong>
|
|
Cell 67: 1021-1027, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1659948/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1659948</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1659948" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0092-8674(91)90374-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="47" class="mim-anchor"></a>
|
|
<a id="Ptacek1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ptacek, L. J., Gouw, L., Kwiencinski, H., McManis, P., Mendell, J. R., Barohn, A. L., Jr., Robertson, M., Leppert, M. F.
|
|
<strong>Sodium channel mutations in paramyotonia congenita and hyperkalemic periodic paralysis.</strong>
|
|
Ann. Neurol. 33: 300-307, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8388676/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8388676</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8388676" 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/ana.410330312" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="48" class="mim-anchor"></a>
|
|
<a id="Ptacek1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ptacek, L. J., Tawil, R., Griggs, R. C., Meola, G., McManis, P., Barohn, R. J., Mendell, J. R., Harris, C., Spitzer, R., Santiago, F., Leppert, M. F.
|
|
<strong>Sodium channel mutations in acetazolamide-responsive myotonia congenita, paramyotonia congenita, and hyperkalemic periodic paralysis.</strong>
|
|
Neurology 44: 1500-1503, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8058156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8058156</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8058156" 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.44.8.1500" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="49" class="mim-anchor"></a>
|
|
<a id="Ricker1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ricker, K., Moxley, R. T., III, Heine, R., Lehmann-Horn, F.
|
|
<strong>Myotonia fluctuans: a third type of muscle sodium channel disease.</strong>
|
|
Arch. Neurol. 51: 1095-1102, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7980103/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7980103</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7980103" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archneur.1994.00540230033009" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="50" class="mim-anchor"></a>
|
|
<a id="Rojas1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rojas, C. V., Wang, J., Schwartz, L. S., Hoffman, E. P., Powell, B. R., Brown, R. H., Jr.
|
|
<strong>A met-to-val mutation in the skeletal muscle Na+ channel alpha-subunit in hyperkalaemic periodic paralysis.</strong>
|
|
Nature 354: 387-389, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1659668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1659668</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1659668" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/354387a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="51" class="mim-anchor"></a>
|
|
<a id="Rojas1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rojas, C. V.
|
|
<strong>Personal Communication.</strong>
|
|
Pittsburgh, Pa. 2/6/1992.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="52" class="mim-anchor"></a>
|
|
<a id="Rosenfeld1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rosenfeld, J., Sloan-Brown, K., George, A. L., Jr.
|
|
<strong>A novel muscle sodium channel mutation causes painful congenital myotonia.</strong>
|
|
Ann. Neurol. 42: 811-814, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9392583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9392583</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9392583" 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/ana.410420520" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="53" class="mim-anchor"></a>
|
|
<a id="Rossignol2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rossignol, E., Mathieu, J., Thiffault, I., Tetreault, M., Dicaire, M.-J., Chrestian, N., Dupre, N., Puymirat, J., Brais, B.
|
|
<strong>A novel founder SCN4A mutation causes painful cold-induced myotonia in French-Canadians.</strong>
|
|
Neurology 69: 1937-1941, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17998485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17998485</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17998485" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000290831.08585.2c" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="54" class="mim-anchor"></a>
|
|
<a id="Rudolph1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rudolph, J. A., Spier, S. J., Byrns, G., Hoffman, E. P.
|
|
<strong>Linkage of hyperkalaemic periodic paralysis in Quarter horses to the horse adult skeletal muscle sodium channel gene.</strong>
|
|
Anim. Genet. 23: 241-250, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1323940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1323940</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1323940" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2052.1992.tb00136.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="55" class="mim-anchor"></a>
|
|
<a id="Rudolph1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rudolph, J. A., Spier, S. J., Byrns, G., Rojas, C. V., Bernoco, D., Hoffman, E. P.
|
|
<strong>Periodic paralysis in Quarter horses: a sodium channel mutation disseminated by selective breeding.</strong>
|
|
Nature Genet. 2: 144-147, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1338908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1338908</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1338908" 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/ng1092-144" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="56" class="mim-anchor"></a>
|
|
<a id="Sasaki1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sasaki, R., Takano, H., Kamakura, K., Kaida, K., Hirata, A., Saito, M., Tanaka, H., Kuzuhara, S., Tsuji, S.
|
|
<strong>A novel mutation in the gene for the adult skeletal muscle sodium channel alpha-subunit (SCN4A) that causes paramyotonia congenita of von Eulenburg.</strong>
|
|
Arch. Neurol. 56: 692-696, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369308/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369308</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10369308" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archneur.56.6.692" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="57" class="mim-anchor"></a>
|
|
<a id="Sillen1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sillen, A., Wadelius, C., Sundvall, M., Ahlsten, G., Gustavson, K. H.
|
|
<strong>Hyperkalemic periodic paralysis caused by recurring mutation in the adult muscle sodium channel alpha-subunit gene.</strong>
|
|
Genet. Counsel. 7: 267-275, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8985730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8985730</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8985730" 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="58" class="mim-anchor"></a>
|
|
<a id="Sokolov2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sokolov, S., Scheuer, T., Catterall, W. A.
|
|
<strong>Gating pore current in an inherited ion channelopathy.</strong>
|
|
Nature 446: 76-78, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17330043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17330043</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17330043" 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/nature05598" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="59" class="mim-anchor"></a>
|
|
<a id="Sugiura2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sugiura, Y., Aoki, T., Sugiyama, Y., Hida, C., Ogata, M., Yamamoto, T.
|
|
<strong>Temperature-sensitive sodium channelopathy with heat-induced myotonia and cold-induced paralysis.</strong>
|
|
Neurology 54: 2179-2181, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10851391/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10851391</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10851391" 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.54.11.2179" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="60" class="mim-anchor"></a>
|
|
<a id="Sugiura2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sugiura, Y., Makita, N., Li, L., Noble, P. J., Kimura, J., Kumagai, Y., Soeda, T., Yamamoto, T.
|
|
<strong>Cold induces shifts of voltage dependence in mutant SCN4A, causing hypokalemic periodic paralysis.</strong>
|
|
Neurology 61: 914-918, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14557559/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14557559</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14557559" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000086820.54065.a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="61" class="mim-anchor"></a>
|
|
<a id="Tahmoush1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tahmoush, A. J., Schaller, K. L., Zhang, P., Hyslop, T., Heiman-Patterson, T., Caldwell, J. H.
|
|
<strong>Muscle sodium channel inactivation defect in paramyotonia congenita with the thr1313-to-met mutation.</strong>
|
|
Neuromusc. Disord. 4: 447-454, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7533571/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7533571</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7533571" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0960-8966(94)90083-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="62" class="mim-anchor"></a>
|
|
<a id="Tsujino2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tsujino, A., Maertens, C., Ohno, K., Shen, X.-M., Fukuda, T., Harper, C. M., Cannon, S. C., Engel, A. G.
|
|
<strong>Myasthenic syndrome caused by mutation of the SCN4A sodium channel.</strong>
|
|
Proc. Nat. Acad. Sci. 100: 7377-7382, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12766226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12766226</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12766226[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=12766226" 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.1230273100" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="63" class="mim-anchor"></a>
|
|
<a id="Venance2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Venance, S. L., Jurkat-Rott, K., Lehmann-Horn, F., Tawil, R.
|
|
<strong>SCN4A-associated hypokalemic periodic paralysis merits a trial of acetazolamide.</strong>
|
|
Neurology 63: 1977 only, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15557532/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15557532</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15557532" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000143068.99794.5b" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="64" class="mim-anchor"></a>
|
|
<a id="Vicart2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vicart, S., Sternberg, D., Fournier, E., Ochsner, F., Laforet, P., Kuntzer, T., Eymard, B., Hainque, B., Fontaine, B.
|
|
<strong>New mutations of SCN4A cause a potassium-sensitive normokalemic periodic paralysis.</strong>
|
|
Neurology 63: 2120-2127, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15596759/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15596759</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15596759" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000145768.09934.ec" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="65" class="mim-anchor"></a>
|
|
<a id="Wang1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wang, D. W., VanDeCarr, D., Ruben, P. C., George, A. L., Jr., Bennett, P. B.
|
|
<strong>Functional consequences of a domain 1/S6 segment sodium channel mutation associated with painful congenital myotonia.</strong>
|
|
FEBS Lett. 448: 231-234, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10218481/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10218481</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10218481" 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/s0014-5793(99)00338-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="66" class="mim-anchor"></a>
|
|
<a id="Wang1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wang, J., Rojas, C. V., Zhou, J., Schwartz, L. S., Nicholas, H., Hoffman, E. P.
|
|
<strong>Sequence and genomics structure of the human adult skeletal muscle sodium channel alpha subunit gene on 17q.</strong>
|
|
Biochem. Biophys. Res. Commun. 182: 794-801, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1310396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1310396</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1310396" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0006-291x(92)91802-w" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="67" class="mim-anchor"></a>
|
|
<a id="Wu2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wu, F., Mi, W., Fu, Y., Struyk, A., Cannon, S. C.
|
|
<strong>Mice with an NaV1.4 sodium channel null allele have latent myasthenia, without susceptibility to periodic paralysis.</strong>
|
|
Brain 139: 1688-1699, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27048647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27048647</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27048647[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=27048647" 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/aww070" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="68" class="mim-anchor"></a>
|
|
<a id="Yamada1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yamada, T., Ochi, H., Hara, H., Yoshimura, T., Kobayashi T.
|
|
<strong>A skeletal muscle sodium channel mutation in a Japanese family with paramyotonia congenita.</strong>
|
|
J. Neurol. Sci. 133: 192-193, 1995.
|
|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8583225/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8583225</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8583225" 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/10.1016/0022-510x(95)00166-y" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="69" class="mim-anchor"></a>
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<a id="Zaharieva2016" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
|
Zaharieva, I. T., Thor, M. G., Oates, E. C., van Karnebeek, C., Hendson, G., Blom, E., Witting, N., Rasmussen, M., Gabbett, M. T., Ravenscroft, G., Sframeli, M., Suetterlin, K., and 28 others.
|
|
<strong>Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy.</strong>
|
|
Brain 139: 674-691, 2016.
|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26700687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26700687</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26700687[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=26700687" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/brain/awv352" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 05/05/2023
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 04/28/2023<br>Cassandra L. Kniffin - updated : 2/11/2016<br>Cassandra L. Kniffin - updated : 10/15/2015<br>Cassandra L. Kniffin - updated : 5/8/2013<br>Cassandra L. Kniffin - updated : 4/18/2011<br>Cassandra L. Kniffin - updated : 3/11/2010<br>Cassandra L. Kniffin - updated : 10/27/2009<br>Cassandra L. Kniffin - updated : 4/6/2009<br>Cassandra L. Kniffin - updated : 10/24/2008<br>Patricia A. Hartz - updated : 7/22/2008<br>Marla J. F. O'Neill - updated : 4/24/2008<br>Cassandra L. Kniffin - updated : 3/31/2008<br>Cassandra L. Kniffin - updated : 6/29/2007<br>Ada Hamosh - updated : 6/20/2007<br>Cassandra L. Kniffin - updated : 7/12/2005<br>Cassandra L. Kniffin - updated : 5/9/2005<br>Cassandra L. Kniffin - updated : 3/16/2005<br>Cassandra L. Kniffin - updated : 1/27/2005<br>Cassandra L. Kniffin - reorganized : 1/28/2004<br>Victor A. McKusick - updated : 7/14/2003<br>Victor A. McKusick - updated : 9/26/2000
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 7/7/1999
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 07/16/2024
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 12/14/2023<br>carol : 05/09/2023<br>ckniffin : 05/05/2023<br>carol : 05/04/2023<br>ckniffin : 04/28/2023<br>carol : 09/01/2020<br>carol : 09/28/2016<br>carol : 02/16/2016<br>ckniffin : 2/11/2016<br>alopez : 10/16/2015<br>ckniffin : 10/15/2015<br>carol : 4/27/2015<br>ckniffin : 4/21/2015<br>carol : 4/6/2015<br>mcolton : 2/10/2015<br>alopez : 5/14/2013<br>ckniffin : 5/8/2013<br>carol : 11/6/2012<br>terry : 6/7/2012<br>terry : 5/10/2012<br>alopez : 10/26/2011<br>terry : 10/26/2011<br>alopez : 8/31/2011<br>alopez : 8/31/2011<br>wwang : 4/21/2011<br>ckniffin : 4/18/2011<br>ckniffin : 4/7/2010<br>wwang : 3/19/2010<br>ckniffin : 3/11/2010<br>wwang : 11/16/2009<br>ckniffin : 10/27/2009<br>wwang : 4/15/2009<br>ckniffin : 4/6/2009<br>wwang : 11/10/2008<br>ckniffin : 10/24/2008<br>wwang : 7/23/2008<br>terry : 7/22/2008<br>wwang : 4/25/2008<br>terry : 4/24/2008<br>wwang : 4/7/2008<br>ckniffin : 3/31/2008<br>wwang : 7/10/2007<br>ckniffin : 6/29/2007<br>alopez : 6/27/2007<br>terry : 6/20/2007<br>carol : 10/4/2006<br>ckniffin : 7/12/2005<br>tkritzer : 5/13/2005<br>ckniffin : 5/9/2005<br>tkritzer : 3/18/2005<br>ckniffin : 3/16/2005<br>tkritzer : 2/1/2005<br>ckniffin : 1/27/2005<br>terry : 6/28/2004<br>joanna : 3/17/2004<br>carol : 1/28/2004<br>ckniffin : 1/15/2004<br>tkritzer : 7/28/2003<br>terry : 7/14/2003<br>terry : 2/12/2001<br>mgross : 1/30/2001<br>terry : 10/6/2000<br>carol : 10/6/2000<br>carol : 10/6/2000<br>mcapotos : 10/2/2000<br>terry : 9/26/2000<br>alopez : 12/7/1999<br>carol : 7/13/1999<br>kayiaros : 7/8/1999<br>carol : 7/7/1999<br>carol : 7/7/1999<br>carol : 7/7/1999
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 603967
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</span>
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</h3>
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</div>
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<div>
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<h3>
|
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<span class="mim-font">
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SODIUM VOLTAGE-GATED CHANNEL, ALPHA SUBUNIT 4; SCN4A
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
SODIUM CHANNEL, VOLTAGE-GATED, TYPE IV, ALPHA SUBUNIT<br />
|
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NAV1.4
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: SCN4A</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 304737009, 41574007, 702355008, 715788001, 715789009;
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<strong>ICD10CM:</strong> G71.12, G71.19, G72.3;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 17q23.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 17:63,938,554-63,972,918 </span>
|
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</em>
|
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</strong>
|
|
<span class="small">(from NCBI)</span>
|
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</h4>
|
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<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
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</th>
|
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<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="7">
|
|
<span class="mim-font">
|
|
17q23.3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Congenital myopathy 22A, classic
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
620351
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
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</td>
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</tr>
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
Congenital myopathy 22B, severe fetal
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
620369
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Hyperkalemic periodic paralysis
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
170500
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Hypokalemic periodic paralysis, type 2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
613345
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Myasthenic syndrome, congenital, 16
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
614198
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Myotonia congenita, atypical, acetazolamide-responsive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
608390
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Paramyotonia congenita
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
168300
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
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|
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|
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<div>
|
|
<br />
|
|
</div>
|
|
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|
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|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The SCN4A gene encodes the alpha subunit of the skeletal muscle voltage-gated sodium channel Na(v)1.4. This channel is essential for the generation and propagation of the muscle action potential needed for muscle contraction (summary by Zaharieva et al., 2016). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
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|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Wang et al. (1992) deduced the amino acid sequence of the SCN4A gene from adult human skeletal muscle by cross-species PCR-mediated cloning and sequencing of the cDNA. The protein consists of 1,836 residues and shows 93% sequence identity to the alpha subunit from rat adult skeletal muscle and 70% identity to the alpha subunit from other mammalian tissues. Similar results were reported by George et al. (1992). </p><p>Bergareche et al. (2015) found expression of the SCN4A gene in mouse skeletal muscle and brain, as well as in human cerebral cortex, suggesting that it has a role in neuronal tissues. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
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|
|
<div>
|
|
<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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<span class="mim-text-font">
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<p>McClatchey et al. (1992) and George et al. (1993) determined that the SCN4A gene contains 24 exons. </p>
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<br />
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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>Fontaine et al. (1990) cloned portions of the adult SCN4A gene and localized it to chromosome 17 using somatic cell hybrids. One of the probes used in this study showed hybridization also to chromosome 3, probably indicating cross-hybridization with the fetal gene. Using RFLPs, they found that the SCN4A gene was closely linked to the growth hormone gene (GH1; 139250) on 17q (maximum lod = 9.89 at theta = 0.00). Furthermore, with very high odds, the gene was placed between NGFR (162010) and TK1 (188300). </p><p>Using clones of the SCN4A gene, George et al. (1991) found a regional assignment of 17q23.1-q25.3 by study of somatic cell hybrids that retained various portions of human chromosome 17. The growth hormone gene cluster (139250), which spans 47 kb, was assigned to 17q22-q24. Bennani-Baiti et al. (1995) demonstrated that the GH gene cluster and the SCN4A gene colocalized to a single 525-kb YAC. Furthermore, restriction mapping and sequencing demonstrated that the SCN4A gene and the entire GH gene cluster are contained within 100 kb on chromosome 17 and are separated by only 21.5 kb. Remarkably, Bennani-Baiti et al. (1995) found that multiple elements critical to tissue-specific transcriptional activation of the GH gene lie within the SCN4A gene. </p>
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</span>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Heterozygous missense mutations in the SCN4A gene have been identified in a group of related muscular disorders, including hyperkalemic periodic paralysis (HYPP; 170500), paramyotonia congenita (PMC; 168300), a group of disorders classified as potassium-aggravated myotonia (608390), and hypokalemic periodic paralysis type 2 (HOKPP2; 613345). These mutations result in a gain-of-function effect via different mechanisms. Less commonly, biallelic loss-of-function or hypomorphic mutations in the SCN4A gene cause congenital myasthenic syndrome-16 (CMS16; 614198), classic congenital myopathy-22A (CMYO22A; 620351), and severe fetal congenital myopathy-22B (CMYO22B; 620369). The severity of the disorder seems to correlate with the detrimental effect of the mutation on SCN4A function (Cannon, 2016). </p><p>Ackerman and Clapham (1997) gave a comprehensive review of the role of ion channel defects in disease and provided figures illustrating the physiology and structure of ion channels and patch-clamp measurement of ion channel activity. </p><p><strong><em>Hyperkalemic Periodic Paralysis</em></strong></p><p>
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In 3 of 7 unrelated patients with HYPP (170500), Ptacek et al. (1991) identified the same mutation in the SCN4A gene (T704M; 603967.0001). In 9 of 12 families with HYPP, Feero et al. (1993) identified mutations in the SCN4A gene: 3 families had the M1592V mutation (603967.0002) and 6 had the T704M mutation. No mutation was identified in 3 families, 1 of whom did not show linkage to the SCN4A gene, suggesting genetic heterogeneity. Jurkat-Rott et al. (2000) stated that 5 mutations in the SCN4A gene had been reported in HYPP patients, none of which was directly located in the voltage sensors. </p><p><strong><em>Paramyotonia Congenita</em></strong></p><p>
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In patients with paramyotonia congenita (163800), McClatchey et al. (1992) identified 2 point mutations in the III-IV cytoplasmic loop region of the SCN4A gene (603967.0007-603967.0008), and suggested that these are the first known examples of molecular definition of temperature-sensitive mutations. The authors postulated that the mutations restrict the channel movement in response to transmembrane potential, and that even a minor drop in temperature may impede movement of the loop enough to allow an abnormal sodium flux. </p><p>Gay et al. (2008) reported a female infant with severe fatal neonatal nondystrophic myotonia in whom they identified a heterozygous mutation (N1297K; 603967.0027) in the SCN4A gene. The phenotype showed overlapping features of paramyotonia congenita and hyperkalemic periodic paralysis. </p><p><strong><em>Myotonia, Potassium-Aggravated</em></strong></p><p>
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Lerche et al. (1993) identified heterozygous mutations in the same codon of the SCN4A gene (G1306V, 603967.0007; G1306A, 603967.0012; and G1306E, 603967.0025) in patients with exercise and potassium-aggravated myotonia, myotonia fluctuans, and myotonia permanens, respectively (see 608390). Patch-clamp recordings on patient muscle samples showed slower sodium fast channel inactivation and an increase in late channel opening, resulting in a steady-state inward current, sustained muscle depolarization, and muscle fiber hyperexcitability. The findings indicated that SCN4A residue 1306 is important for sodium channel inactivation. </p><p>In a family with dominantly inherited potassium-aggravated myotonia (608390), Orrell et al. (1998) found a heterozygous mutation in the SCN4A gene (603967.0009). The myotonic phenotype was characterized by painful cramps, stiffness without weakness, fluctuation of symptoms, and cold sensitivity. </p><p><strong><em>Hypokalemic Periodic Paralysis</em></strong></p><p>
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In 4 affected individuals of family with hypokalemic periodic paralysis, Bulman et al. (1999) identified a heterozygous missense mutation in the SCN4A gene (603967.0015). In several families with HOKPP in which defects of the CACNL1A3 gene (CACNA1S; 114208) had been excluded, Jurkat-Rott et al. (2000) identified 2 heterozygous disease-causing missense mutations in the SCN4A gene (603967.0016-603967.0017). This form of HOKPP did not differ clinically from the form of the disorder due to mutations in the gene for CACNL1A3. </p><p>Sokolov et al. (2007) showed that, in contrast with the well-established paradigm in which alterations in control of ion conductance through the central pore of ion channels impair cell function, 3 mutations in gating charge-carrying arginine residues in an S4 segment that cause hypokalemic periodic paralysis (HOKPP) induce a hyperpolarization-activated cationic leak through the voltage sensor of the skeletal muscle Nav1.4 channel. This gating pore current is active at the resting membrane potential and closed by depolarizations that activate the voltage sensor. It has similar permeability to sodium, potassium, and cesium ions, but the organic monovalent cations tetraethylammonium and N-methyl-D-glucamine are much less permeant. The inorganic divalent cations barium, calcium, and zinc are not detectably permeant and block the gating pore at millimolar concentrations. Sokolov et al. (2007) concluded that their results revealed gating pore current in naturally occurring disease mutations of an ion channel and showed a clear correlation between mutations that cause gating pore current and hypokalemic periodic paralysis. This gain-of-function gating pore current would contribute in an important way to the dominantly inherited membrane depolarization, action potential failure, flaccid paralysis, and cytopathology that are characteristic of hypokalemic periodic paralysis. Sokolov et al. (2007) postulated that their observations might be generalizable to other ion channelopathies. </p><p>Matthews et al. (2009) identified mutations in the CACNA1S (114208) or SCN4A gene in 74 (almost 90%) of 83 patients with HOKPP. All of the mutations, including 3 novel mutations, affected arginine residues in the S4 voltage sensing region in 1 of the transmembrane domains of each gene. The most common CACNA1S mutations affected residues arg528 (25 cases) and arg1239 (39 cases) (see, e.g., R1239H; 114208.0001 and R528H; 114208.0003). The most common SCN4A mutations affected residues arg672 (see, e.g., 603967.0016) and arg1132. The findings supported the hypothesis that loss of positive charge in S4 voltage sensors is important to the pathogenesis of this disorder. (Sokolov et al., 2007). </p><p>Francis et al. (2011) demonstrated that an R1132Q mutation (603967.0030) in the domain III voltage sensor domain of SCN4A found in a family with HOKPP created an anomalous gating pore current similar to that observed by Sokolov et al. (2007). This current is sufficient to depolarize and render the muscle fiber inexcitable particularly during low external potassium. The findings suggested a mechanism for loss of sarcolemmal excitability during attacks of weakness in HOKPP. In contrast, the R1148C mutation (603967.0003) causing PMC does not result in gating pore abnormalities. </p><p><strong><em>Congenital Myasthenic Syndrome 16</em></strong></p><p>
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In a patient with congenital myasthenic syndrome-16 (CMS16; 614198) associated with fatigable generalized weakness and recurrent attacks of respiratory and bulbar paralysis since birth, Tsujino et al. (2003) identified compound heterozygous variants in the SCN4A gene (V1442E, 603967.0018 and S246L, 603967.0031). </p><p>In a 57-year-old woman, born of consanguineous parents, with CMS16, Arnold et al. (2015) identified a homozygous missense mutation in the SCN4A gene (R1457H; 603967.0032). In vitro electrophysiologic studies showed that the mutation caused a 25-mV hyperpolarizing shift in the voltage dependence of inactivation, resulting in enhanced fast inactivation as well as slowed recovery from fast inactivation. In addition, repetitive stimuli elicited markedly weaker current responses. These changes resulted in reduced channel availability, which could explain the patient's muscle weakness. The unaffected parents and sibs were heterozygous for the mutation. </p><p>In a 26-year-old Lebanese woman, born of consanguineous parents, with CMS16 and features of normokalemic periodic paralysis, Habbout et al. (2016) identified a homozygous missense mutation in the SCN4A gene (R1454W; 603967.0041). Each unaffected parent was heterozygous for the mutation. In vitro functional expression studies showed that the mutation resulted in a loss-of-function effect, with slowed current decay, slowed fast inactivation, and increased activation time compared to wildtype. Slowed inactivation was also disturbed. Current density was not affected, but there was a decrease in current amplitude in response to repetitive stimulation above 10 Hz. The findings thus showed a combination of gating behaviors that favor the inactivation state; defective inactivation may induce fatigable weakness during muscle firing. </p><p><strong><em>Congenital Myopathy 22A, Classic</em></strong></p><p>
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In 8 patients from 4 unrelated families (families 1-4) with classic congenital myopathy-22A (CMYO22A; 620351), Zaharieva et al. (2016) identified homozygous or compound heterozygous mutations in the SCN4A gene (see, e.g., 603967.0034-603967.0035). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in all families. There were missense, nonsense, frameshift, and splice site mutations distributed throughout the gene. Electrophysiologic studies of the missense variants in HEK293 cells showed that they caused a loss-of-function effect of varying degrees. All patients carried 1 mutation that resulted in a completely nonfunctional channel in combination with a hypomorphic allele. None of the carrier parents was affected, indicating that loss of function in only 1 SCN4A allele is insufficient to cause a clinical phenotype. </p><p>In 2 brothers, born of unrelated parents of East Indian descent, with CMYO22A, Gonorazky et al. (2017) identified compound heterozygous missense mutations in the SCN4A gene (C375R, 603967.0039 and R1142Q, 603967.0040). The mutations, which were found by exome sequencing, segregated with the disorder in the family. In vitro electrophysiologic studies in HEK293 cells showed that the C375R mutation abolished sodium activity and caused a complete loss of SCN4A function, whereas the R1142Q mutation was hypomorphic with reduced peak current densities due to a 4-mV depolarizing shift of activation. Fast inactivation properties of the R1142Q mutant channel were also mildly affected. </p><p>In an 18-year-old girl, born of unrelated parents, with CMYO22A, Berghold et al. (2022) identified compound heterozygous missense mutations in the SCN4A gene (R1454W, 603967.0041 and N1205K, 603967.0042). The mutations, which were found by whole-exome sequencing, were inherited from the unaffected parents. R1454W, located in the voltage sensor of domain IV, had been demonstrated to be a loss-of-function variant by Habbout et al. (2016). The N1205K, located in a region forming the channel pore, was a novel variant. Functional studies of N1205K were not performed, but it was predicted to cause a loss of function based on studies of paralogous variants in other SCNA genes. </p><p><strong><em>Congenital Myopathy 22B, Severe Fetal</em></strong></p><p>
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In 6 patients from 2 unrelated families (families 5 and 6) with severe fetal congenital myopathy-22B (CMYO22B; 620369) resulting in death in utero or in the perinatal period, Zaharieva et al. (2016) identified homozygous or compound heterozygous mutations in the SCN4A gene. Three sibs in family 5 carried a homozygous missense mutation (P382T; 603967.0036) that was demonstrated to result in a complete loss of function with no detectable sodium current when expressed in HEK293 cells. Three sibs in family 6 were compound heterozygous for a missense mutation (M203K; 603967.0037) that was demonstrated to have a hypomorphic effect on channel function, and a nonsense mutation (Y1593X; 603967.0038) that was predicted to result in a complete loss of channel function. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in all families. None of the carrier parents was affected, indicating that loss of function in only 1 SCN4A allele is insufficient to cause a clinical phenotype. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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For discussion of a possible association between essential tremor (see, e.g., ETM1, 190300) and variation in the SCN4A gene, see 603967.0033.</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>Rudolph et al. (1992, 1992) identified a mutation in the SCN4A gene in Quarter horses with HYPP (see 170500). </p><p>Hayward et al. (2008) introduced a missense substitution corresponding to the human M1592V mutation into the mouse Scn4a gene and found that few homozygous mutant (m/m) mice survived and those that did showed fixed limb weakness, muscle atrophy, and abnormal muscle morphology. Heterozygous (+/m) mice showed only a mild myopathy at 4 months of age, but myopathic changes developed with age and included electrical myotonia, fiber type switching to a more oxidative type, size variation, and internalized nuclei, and +/m muscle developed less tetanic force and exhibited slower relaxation compared with muscle from wildtype controls. Rapid and sustained weakness of isolated mutant muscle was induced when the extracellular K+ concentration was increased to that observed in exercising human muscle interstitium, and weakness was exacerbated by lowering extracellular Ca(2+) and by partial inhibition of the Na+/K+ pump. Mutant muscle recovered from stimulation-induced fatigue more slowly than did control muscle, particularly in the presence of high extracellular K+. Hayward et al. (2008) concluded that this myotonia is consistent with persistent Na+ influx through the noninactivating mutant Na+ channel that mildly depolarizes the membrane and thereby increases excitability. </p><p>Wu et al. (2016) found that mice homozygous for a null Scn4a allele (exon 12 deletion) did not survive beyond postnatal day 2. Heterozygous mutant mice showed no gross motor deficits. Electrophysiologic studies in heterozygous mice showed that the sodium current amplitude was decreased about 2-fold and subtle myasthenic features were observed on repetitive stimulation at high frequencies. The myasthenic features were termed 'pseudo-myasthenic' because the defect resided in the intrinsic excitability of the muscle fiber rather than at the postsynaptic endplate potential. Heterozygosity for the loss-of-function allele was not sufficient to cause hypokalemic periodic paralysis. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>42 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 HYPERKALEMIC PERIODIC PARALYSIS</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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PARAMYOTONIA CONGENITA/HYPERKALEMIC PERIODIC PARALYSIS, 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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SCN4A, THR704MET
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<br />
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SNP: rs80338957,
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ClinVar: RCV000006254, RCV000006255, RCV000255373, RCV000763020, RCV002291266, RCV003231090, RCV004532296
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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 of 7 unrelated patients with hyperkalemic periodic paralysis (HYPP; 170500), Ptacek et al. (1991) identified a heterozygous C-to-T change at a CpG dimer in the SCN4A gene, resulting in a thr704-to-met (T704M) substitution in S5 of domain II in the membrane-spanning segment of the sodium channel protein. All 3 patients had prominent fixed muscle weakness, whereas the remaining 4 did not. In 2 of the families, the mutation cosegregated with HYPP; in the third it appeared to be a de novo mutation. The authors noted that threonine-704 is absolutely conserved in sodium channel genes across highly divergent species. </p><p>Sillen et al. (1996) found the T704M mutation in 2 Swedish families with HYPP. The mutation was linked to different microsatellite alleles, suggesting that the mutation may have arisen independently in the 2 families. </p><p>In a family with features of both HYPP and paramyotonia congenita (PMC; 168300), which the authors termed 'paralysis periodica paramyotonica,' Kim et al. (2001) identified the T704M mutation. Both exercise sensitivity and temperature sensitivity were present, and the authors commented on the phenotypic variation resulting from this mutation. </p><p>In an Italian kindred in which 9 members were affected with a severe form of HYPP/PMC, Brancati et al. (2003) found the T704M mutation. Onset of the disorder was in the first months of life in all affected patients and the episodes of paralysis increased in severity and frequency, sometimes up to several times a day, with age. </p><p>Miller et al. (2004) identified the T704M mutation in affected members of 10 kindreds with HYPP. All patients had onset before 1 year of age and overall showed only a 50% chance of favorable response to acetazolamide. </p><p>Hisama (2005) described a 7-generation family in which multiple members were affected with a complicated neurologic phenotype including variable features of neuropathy, myotonia, and periodic paralysis. The same family had been described in the medical literature since 1934. The proband had late-onset demyelinating Charcot-Marie-Tooth disease (CMT1B; 118200), muscle cramping, and myotonia. His sister had HYPP, and his father had severe childhood-onset CMT and periodic paralysis. Multiple other relatives had similar features of 1 or both disorders. Molecular analysis identified a missense mutation in the MPZ gene (159440) in the proband and the SCN4A T704M mutation in the sister; the father was deceased. One other family member tested had the MPZ mutation, and 4 other family members had the SCN4A mutation. Hisama (2005) commented on the unusual occurrence of 2 genetically unlinked neurologic disorders in this family and emphasized the diagnostic difficulties. </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 HYPERKALEMIC PERIODIC PARALYSIS</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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PARAMYOTONIA CONGENITA/HYPERKALEMIC PERIODIC PARALYSIS, 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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SCN4A, MET1592VAL
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<br />
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SNP: rs80338962,
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ClinVar: RCV000006256, RCV000006257, RCV000516497, RCV000763018, RCV005016245
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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 patient with familial hyperkalemic periodic paralysis (HYPP; 170500), Rojas et al. (1991) identified a heterozygous A-to-G transition in the SCN4A gene, resulting in a met-to-val substitution in a highly conserved region of the alpha subunit, predicted to be in S6 of transmembrane domain IV. The same change was found as a new mutation in a sporadic case. Rojas (1992) stated that the transition occurred at nucleotide 4774 and changed met to val at residue 1592 (M1592V). Heine et al. (1993) found the M1592V mutation in 6 families with a myotonic, nondystrophic form of HYPP. </p><p>Kelly et al. (1997) described a large kindred in which affected members were phenotypically heterogeneous with episodic potassium-sensitive paralysis as well as stiffness and weakness induced by exercise and cold, suggesting a combined paramyotonia congenita (PMC; 168300)/HYPP phenotype. Affected members had a heterozygous M1592V mutation, and the authors commented on the phenotypic variation associated with this 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>.0003 PARAMYOTONIA CONGENITA</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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SCN4A, ARG1448CYS
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<br />
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SNP: rs121908544,
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ClinVar: RCV000006258, RCV000206951, RCV000255921, RCV001813736, RCV003989102
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a family with paramyotonia congenita (PMC; 168300), Ptacek et al. (1992) identified a heterozygous mutation in the SCN4A gene, resulting in an arg1448-to-cys (R1448C) substitution. This codon is a highly conserved residue in the S4 helix of domain IV in the adult skeletal muscle sodium channel. </p><p>In 2 other families with PMC, Ptacek et al. (1992) found a heterozygous mutation in the same codon, resulting in an arg1448-to-his (R1448H) substitution (see 603967.0004). </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 PARAMYOTONIA CONGENITA</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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SCN4A, ARG1448HIS
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<br />
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SNP: rs121908545,
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ClinVar: RCV000006259, RCV000206992, RCV000517055, RCV000662289, RCV001775065, RCV002267600, RCV002288469, RCV003483425, RCV004734499
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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 families with paramyotonia congenita (PMC; 168300), Ptacek et al. (1992) found a heterozygous mutation in the SCN4A gene, resulting in an arg1448-to-his (R1448H) substitution. </p><p>Meyer-Kleine et al. (1994) found that the R1448H mutation is exceptionally frequent in the Ravensberger Land region of northwest Germany, where it exists on a specific SCN4A microsatellite haplotype, indicating a founder effect within this subpopulation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 PARAMYOTONIA CONGENITA/HYPERKALEMIC PERIODIC PARALYSIS</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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SCN4A, ALA1156THR
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<br />
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SNP: rs80338958,
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gnomAD: rs80338958,
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ClinVar: RCV000006260, RCV000020271, RCV000516392, RCV001004616, RCV002496281, RCV003162214, RCV004545720, RCV004595874
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In a family of Finnish extraction whose affected members displayed an unusual mixture of clinical features of both paramyotonia congenita (PMC; 168300) and hyperkalemic periodic paralysis (HYPP; 170500), McClatchey et al. (1992) identified a heterozygous c.3466G-A transition in the SCN4A gene, resulting in an ala1156-to-thr (A1156T) substitution. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0006 PARAMYOTONIA CONGENITA/MYOTONIA CONGENITA</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 FLUCTUANS, 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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SCN4A, SER804PHE
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<br />
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SNP: rs121908546,
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gnomAD: rs121908546,
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ClinVar: RCV000006261, RCV000489309, RCV001799586, RCV003505081
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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 an Italian family with features of both paramyotonia congenita (PMC; 168300) and myotonia congenita (see 608390), McClatchey et al. (1992) identified a heterozygous c.2411C-T transition in the SCN4A gene, resulting in a ser804-to-phe (S804F) substitution predicted to be in the cytoplasmic face of the sixth transmembrane segment of domain II. A serine had been present at this position in all sodium channels sequenced to that date. </p><p>Ricker et al. (1994) found the S804F mutation in a family with the 'myotonia fluctuans' (608390) phenotype. See also 603967.0012. </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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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 PARAMYOTONIA CONGENITA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
MYOTONIA, POTASSIUM-AGGRAVATED, INCLUDED
|
|
</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, GLY1306VAL
|
|
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|
<br />
|
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|
|
SNP: rs80338792,
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|
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|
|
gnomAD: rs80338792,
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|
|
ClinVar: RCV000006264, RCV000006265, RCV000479620, RCV000690377, RCV002267601, RCV005016246
|
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|
|
|
|
</span>
|
|
</div>
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|
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Belgian family with paramyotonia congenita (PMC; 168300), McClatchey et al. (1992) identified a heterozygous c.3917G-T transversion in the SCN4A gene, resulting in a gly1306-to-val (G1306V) substitution. The mutation affected a highly conserved residue in the III-IV cytoplasmic loop, a portion of the sodium channel thought to pivot in response to membrane depolarization, thereby blocking and inactivating the channel. Muscle weakness was not reported. The authors suggested that this is a temperature-sensitive mutation. </p><p>Lerche et al. (1993) identified a heterozygous G1306V substitution in a mother and son with potassium-aggravated myotonia (608390). Muscle stiffness in these individuals was also aggravated by exercise, but not by cold. Muscle weakness was not reported. Patch-clamp recordings on patient muscle samples showed slower sodium fast channel inactivation and an increase in late channel opening, resulting in a steady-state inward current, sustained muscle depolarization, and muscle fiber hyperexcitability. Lerche et al. (1993) identified different pathogenic mutations in the same codon (G1306A; 603967.0012 and G1306E; 603967.0025) in other families with similar disorders, indicating that residue 1306 is important for sodium channel inactivation. </p><p>Dupre et al. (2009) reported French Canadian patients with myotonia associated with the G1306V mutation. They had moderate myotonia with mild muscle hypertrophy. They noted exacerbation of symptoms with cold temperatures but no paradoxical myotonia. Female patients showed dramatic symptom improvement after menopause. </p>
|
|
</span>
|
|
</div>
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|
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|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 PARAMYOTONIA CONGENITA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
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<div>
|
|
<span class="mim-text-font">
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|
|
|
SCN4A, THR1313MET
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<br />
|
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|
|
SNP: rs121908547,
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|
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|
|
gnomAD: rs121908547,
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|
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ClinVar: RCV000006266, RCV000414134, RCV000540455, RCV000763019, RCV002267602, RCV003455986, RCV004532297, RCV004786239
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|
|
|
|
|
</span>
|
|
</div>
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|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with paramyotonia congenita (PMC; 168300) living in North America, McClatchey et al. (1992) identified a heterozygous C-to-T transition in the SCN4A gene, resulting in a thr1313-to-met (T1313M) substitution. The mutation affected a highly conserved residue in the III-IV cytoplasmic loop of the protein. </p><p>Tahmoush et al. (1994) identified the T1313M mutation in a 3-generation paramyotonia congenita family with 5 affected individuals. Single-channel recordings of normal and abnormal sodium channels in myotubes in tissue-cultured muscles derived from the proband showed that abnormal sodium channels at 22 degrees centigrade exhibited long duration and late openings. </p><p>Yamada et al. (1995) found the same mutation in a Japanese woman and her son who had PMC manifested by difficulty in closure of eyelids or chewing, and stiffness and weakness in hands aggravated by cold beginning at about 7 years of age. </p><p>Matthews et al. (2011) reported a family with PMC due to the heterozygous T1313M mutation. Before correct diagnosis, the youngest affected individual presented with neonatal inspiratory stridor and poor feeding. Laryngoscopy showed findings consistent with laryngomalacia. He continued to have stridor for the first 6 months of life, and later motor milestones were mildly delayed. In early childhood, he was noted to have frequent episodic muscle weakness and stiffness associated with cold weather. At age 4 years, he continued to have episodes of inspiratory stridor exacerbated by viral illness, cold weather, and prolonged laughing or crying. His mother, grandfather, and great-uncle reported similar episodes of muscle stiffness and weakness exacerbated by cold and exercise. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 MYOTONIA, POTASSIUM-AGGRAVATED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PARAMYOTONIA CONGENITA, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, VAL1589MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908548,
|
|
|
|
|
|
|
|
ClinVar: RCV000006267, RCV000006268, RCV000518064, RCV000800365, RCV001849259
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a father and daughter (family SCM8) with potassium-aggravated myotonia (608390) without muscle weakness, Heine et al. (1993) identified a heterozygous c.4765G-A transition in exon 24 of the SCN4A gene, predicted to result in a val1589-to-met (V1589M) substitution. The family had previously been reported by Iaizzo et al. (1991) as family MyC2. The myotonia in this family was aggravated by both cold and potassium loading, similar to paramyotonia congenita (PMC; 168300). The mutation is located within transmembrane segment S6 of channel repeat IV close to the cytoplasmic surface, a region thought to act as acceptor of the inactivation gate of the channel. An increase in the number of noninactivating sodium channels had been demonstrated in earlier electrophysiologic studies on excised muscle from the index patient. The nearby M1592V (603967.0002) mutation causes hyperkalemic periodic paralysis (170500) of the myotonic, nondystrophic form. </p><p>Orrell et al. (1998) identified the V1589M mutation in a family in which 9 members spanning 4 generations had cramps in the fingers, toes, and eyelids, consistent with potassium-aggravated myotonia. A reduction in amplitude of compound muscle action potential on cooling and administration of potassium was demonstrated. The authors noted that the phenotype in this family was milder than that in the family reported by Heine et al. (1993). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MYOTONIA CONGENITA, ATYPICAL, ACETAZOLAMIDE-RESPONSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, ILE1160VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908549,
|
|
|
|
|
|
|
|
ClinVar: RCV000006269, RCV000497702, RCV003505082
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with acetazolamide-responsive myotonia congenita without periodic paralysis (see 608390), Ptacek et al. (1994) identified a heterozygous c.3555A-G transition in the SCN4A gene, predicted to result in an ile1160-to-val (I1160V) substitution. This isoleucine is a highly conserved residue, cosegregated with the disease phenotype in one studied kindred, and was not present in samples from 100 unrelated unaffected individuals. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 PARAMYOTONIA CONGENITA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, LEU1433ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908550,
|
|
|
|
|
|
|
|
ClinVar: RCV000006270, RCV002267603
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Ptacek et al. (1993) reported that a heterozygous leu-to-arg (L1433R) change in the SCN4A gene results in the paramyotonia congenita (PMC; 168300) phenotype. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 MYOTONIA FLUCTUANS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, GLY1306ALA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80338792,
|
|
|
|
|
|
gnomAD: rs80338792,
|
|
|
|
|
|
ClinVar: RCV000153907, RCV000525753, RCV001535772, RCV001799587, RCV002288470
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 3 families with a muscle sodium channel disorder termed 'myotonia fluctuans' (see 608390), Ricker et al. (1994) identified a heterozygous c.3917G-C transversion in exon 22 of the SCN4A gene, resulting in a gly1306-to-ala (G1306A) substitution. The mutation resides in the region of the sodium channel protein containing the cytoplasmic loop between domains 3 and 4. The phenotype consists of fluctuating myotonia of varying severity, a warm-up phenomenon, worsening of myotonia after potassium loading, increased myotonia of delayed onset following exercise, and no significant increase of myotonia following exposure to cold. Muscle weakness did not occur. One other family with the same phenotype had a previously described mutation of the sodium channel (603967.0006). </p><p>Lerche et al. (1993) identified the G1306A mutation in a patient with myotonia fluctuans. Patch-clamp recordings on patient muscle samples showed slower sodium fast channel inactivation and an increase in late channel opening, resulting in a steady-state inward current, sustained muscle depolarization, and muscle fiber hyperexcitability. Lerche et al. (1993) identified different pathogenic mutations in the same codon (G1306V; 603967.0007 and G1306E; 603967.0025) in other families with similar disorders, indicating that residue 1306 is important for sodium channel inactivation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 PARAMYOTONIA CONGENITA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, VAL1293ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908551,
|
|
|
|
|
|
gnomAD: rs121908551,
|
|
|
|
|
|
ClinVar: RCV000006272, RCV000396578, RCV000509130, RCV000654659
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 unrelated 3-generation families segregating paramyotonia without cold paralysis (see 168300) as an autosomal dominant trait, Koch et al. (1995) identified a heterozygous c.3877G-A transition in exon 21 of the SCN4A gene, resulting in a val1293-to-ile (V1293I) substitution. The amino acid alteration was not found to be a mild polymorphism in their survey of 200 chromosomes from the German population. The predicted mutation was located at the intracellular phase of segment S6 in domain III of the channel protein. Val1293 is conserved in human, rat, and eel. </p>
|
|
</span>
|
|
</div>
|
|
|
|
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|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 MYOTONIA CONGENITA, ATYPICAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, VAL445MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908552,
|
|
|
|
|
|
gnomAD: rs121908552,
|
|
|
|
|
|
ClinVar: RCV000006273, RCV000255075, RCV000544236, RCV000763021, RCV002267604
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Rosenfeld et al. (1997) reported the first known mutation in the first repeat domain (D1) of the SCN4A gene. The previous conspicuous absence of mutations in this region fueled speculation that mutations in this domain were either inconsequential or possibly lethal. The heterozygous mutation, val445-to-met (V445M), was associated with an unusual form of painful congenital myotonia (see 608390). The distinctive phenotype suggested that the pattern of sodium channel dysfunction might also be unique. </p><p>Wang et al. (1999) characterized the V445M mutation using heterologous expression of recombinant mutant and wildtype skeletal muscle sodium channel alpha subunits. Their findings established that the mutation causes a defect in sodium channel gating that is compatible with a myotonia-producing lesion. The pattern of dysfunction was distinct from other muscle sodium channel mutations, supporting the notion that D1 sodium channel mutations may be associated with unusual phenotypes. They also demonstrated that flecainide effectively suppressed the abnormal channel behavior, consistent with the observed clinical efficacy of the drug in treating the unusual form of myotonia. </p><p>Dupre et al. (2009) reported French Canadian patients with the V445M mutation. The phenotype was characterized by severe and painful generalized myotonia and severe muscle hypertrophy. Ethanol or mexiletine significantly alleviated myotonia in 1 patient. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 HYPOKALEMIC PERIODIC PARALYSIS, TYPE 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, ARG669HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80338784,
|
|
|
|
|
|
gnomAD: rs80338784,
|
|
|
|
|
|
ClinVar: RCV000006274, RCV000206926, RCV003482224, RCV005016247
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Bulman et al. (1999) found a heterozygous arg669-to-his (R669H) mutation in the SCN4A gene in a family in which 4 members had hypokalemic periodic paralysis type 2 (HOKPP2; 613345). </p><p>By in vitro studies, Kuzmenkin et al. (2002) showed that the R669H mutation caused enhanced fast and slow inactivation of the SCN4A sodium channel. The inactivation defect could be alleviated by decreased pH, which may explain why some patients have relief by some physical exercise. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<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>.0016 HYPOKALEMIC PERIODIC PARALYSIS, TYPE 2</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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SCN4A, ARG672HIS
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<br />
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SNP: rs80338788,
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gnomAD: rs80338788,
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ClinVar: RCV000006275, RCV000206975, RCV001532353, RCV002490327, RCV003387718, RCV004798719
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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 (HypoPP29, HypoPP18, and HypoPP105) with hypokalemic periodic paralysis type 2 (HOKPP2; 613345), Jurkat-Rott et al. (2000) identified a heterozygous c.2016G-A transition in exon 12 of the SCN4A gene, resulting in an arg672-to-his (R672H) substitution in the voltage sensor of domain-2. </p><p>By in vitro studies in HEK293 cells, Kuzmenkin et al. (2002) showed that the R672H mutation caused enhanced fast inactivation of the SCN4A sodium channel. The inactivation defect could be alleviated by decreased pH, which may explain why some patients have relief by some physical exercise. </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>.0017 HYPOKALEMIC PERIODIC PARALYSIS, TYPE 2</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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SCN4A, ARG672GLY
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<br />
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SNP: rs80338785,
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ClinVar: RCV000006276, RCV000020262, RCV000206901, RCV001092728
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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 2 multigenerational families (HypoPP106 and HypoPP6) with hypokalemic periodic paralysis type 2 (HOKPP2; 613345), Jurkat-Rott et al. (2000) identified a heterozygous c.2015C-G transversion in the SCN4A gene, resulting in an arg672-to-gly (R672G) substitution in the voltage sensor of domain-2. Excised skeletal muscle fibers from a patient heterozygous for R672G displayed depolarization and weakness in low-potassium extracellular solution. Slowing and smaller size of action potentials were suggestive of excitability of the wildtype channel population only. Alterations found were decisive for the pathogenesis of episodic muscle weakness by reducing the number of excitable sodium channels, particularly at sustained membrane depolarization. This form of the disease was caused by enhanced channel inactivation and current reduction, and showed no myotonia. </p><p>By in vitro studies in HEK293 cells, Kuzmenkin et al. (2002) showed that the R672G mutation caused enhanced slow and fast inactivation of the SCN4A sodium 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>.0018 MYASTHENIC SYNDROME, CONGENITAL, 16</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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SCN4A, VAL1442GLU
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<br />
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SNP: rs121908553,
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ClinVar: RCV000006277, RCV000235023
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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 patient with a congenital myasthenic syndrome-16 (CMS16; 614198) associated with fatigable generalized weakness and recurrent attacks of respiratory and bulbar paralysis since birth, Tsujino et al. (2003) detected compound heterozygosity for 2 variants in the SCN4A gene involving conserved residues not present in 400 normal alleles: a c.4325T-A transversion, resulting in a val1442-to-glu (V1442E) substitution in the S3/S4 extracellular linker in domain IV, and a c.737C-T transition, resulting in a ser246-to-leu (S246L; 603967.0031) change in the S4/S5 cytoplasmic linker in domain I. The genetically engineered V1442E sodium channel expressed in cultured cells showed marked enhancement of fast inactivation close to the resting potential, and enhanced use-dependent inactivation on high-frequency stimulation. The proband's asymptomatic mother and sister were heterozygous for the S246L mutation. Paternal DNA was unavailable for analysis. The authors considered S246L likely to be a benign polymorphism, whereas the V1442E mutation defines a novel disease mechanism and a novel phenotype with myasthenic features. Tsujino et al. (2003) concluded that the inheritance pattern of this congenital myasthenic syndrome could not be unambiguously established. They suggested that the more severe V1442E mutation may be dominant, but it could not be proven because the mutation was observed only in combination with S246L on the other chromosome. </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 PARAMYOTONIA CONGENITA</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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SCN4A, GLY1456GLU
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<br />
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SNP: rs121908554,
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ClinVar: RCV000006278
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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 large Japanese family with paramyotonia congenita (PMC; 168300), Sasaki et al. (1999) identified a heterozygous c.4367G-A change in exon 24 of the SCN4A gene, resulting in a gly1456-to-glu (G1456E) substitution in S4 of domain IV of the channel. Only 3 of 9 affected members reported episodes of severe generalized weakness, which were always after cold exposure. </p><p>In a family with PMC without periodic paralysis, which the authors termed 'pure paramyotonia,' Davies et al. (2000) identified the G1456E mutation. The authors predicted that the mutation would impair voltage sensing or channel inactivation in a temperature-dependent fashion and concluded that exon 24 is a hotspot for paramyotonia mutations. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 HYPOKALEMIC PERIODIC PARALYSIS, TYPE 2</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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|
|
SCN4A, ARG672SER
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<br />
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|
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SNP: rs80338785,
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|
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ClinVar: RCV000006279, RCV000206986, RCV003493408
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In the proband of a family with hypokalemic periodic paralysis type 2 (HOKPP2; 613345), Davies et al. (2001) identified a heterozygous c.2014C-A change in exon 12 of the SCN4A gene, resulting in an arg672-to-ser (R672S) substitution. The patient responded well to acetazolamide. The authors noted that 2 other mutations in the same codon had been reported in HOKPP (see 603967.0016 and 603967.0017). </p><p>Functional expression studies of the R672S sodium channel by Bendahhou et al. (2001) showed a small but significant hyperpolarizing shift in the steady-state fast inactivation, and a dramatic enhancement in channel slow inactivation. The defects are mainly due to a slow recovery of the mutant channels from inactivation. The authors noted that their patient with this mutation had shown a worsening of symptoms from acetazolamide. </p><p>Venance et al. (2004) reported a sporadic patient with HOKPP and the R672S mutation who responded well to acetazolamide. The authors noted the variability in response to the drug and suggested that carbonic anhydrase inhibitors should be considered in patients with HOKPP. </p>
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|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 HYPOKALEMIC PERIODIC PARALYSIS, TYPE 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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|
|
SCN4A, PRO1158SER
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<br />
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|
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SNP: rs121908555,
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|
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ClinVar: RCV000006280, RCV000713100, RCV001210018, RCV002512825
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese family with an unusual form of hypokalemic periodic paralysis type 2 (HOKPP2; 613345), Sugiura et al. (2000) identified a heterozygous c.3472C-T transition in exon 19 of the SCN4A gene, resulting in a pro1158-to-ser (P1158S) substitution between the fourth and fifth transmembrane segments of domain III. The phenotype in this family was unusual in that affected members showed heat-induced myotonia and cold-induced paralysis with hypokalemia. Myotonia lessened with exercise and was alleviated by cold, thus distinguishing the myotonia from paramyotonia congenita (PMC; 168300). Treatment with acetazolamide alleviated the myotonia, but slightly worsened the paralysis. Patients showed seasonal swings with myotonia in the summer and paralysis in the winter, with hypokalemia during the paralytic attacks. </p><p>By functional studies, Sugiura et al. (2003) showed that the P1158S mutation exhibited temperature-dependent negative shifts in the voltage dependence of activation and inactivation as well as a slower rate of inactivation compared to wildtype. </p>
|
|
</span>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 NORMOKALEMIC PERIODIC PARALYSIS, POTASSIUM-SENSITIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, ARG675GLY
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|
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|
|
|
<br />
|
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|
|
SNP: rs121908556,
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|
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|
|
|
gnomAD: rs121908556,
|
|
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|
|
ClinVar: RCV000006281, RCV000206909, RCV001172114, RCV001813957
|
|
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</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 affected members of a family with potassium-sensitive normokalemic periodic paralysis (see HYPP, 170500), Vicart et al. (2004) identified a heterozygous C-to-G transversion in exon 13 of the SCN4A gene, resulting in an arg675-to-gly (R675G) substitution within the membrane-spanning segment S4 of domain II of the protein, which is known to be involved in the voltage sensing of the channel. Acetazolamide therapy was effective in almost all patients. </p><p>Vicart et al. (2004) noted that mutations affecting codon 672--R672H (603967.0016), R672G (603967.0017), and R672S (603967.0020)--and codon 669 (R669H; 603967.0015) affect 2 nearby arginines in segment S4 of domain II and lead to hypokalemic periodic paralysis type 2 (HOKPP2; 613345). </p>
|
|
</span>
|
|
</div>
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<div>
|
|
<br />
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</div>
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</div>
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<div>
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0023 NORMOKALEMIC PERIODIC PARALYSIS, POTASSIUM-SENSITIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
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|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, ARG675GLN
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|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908557,
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|
|
|
|
|
gnomAD: rs121908557,
|
|
|
|
|
|
ClinVar: RCV000006282, RCV000206996, RCV000516541, RCV000543491, RCV003147276, RCV003335018, RCV005025013
|
|
|
|
|
|
</span>
|
|
</div>
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with potassium-sensitive normokalemic periodic paralysis (see HYPP, 170500), Vicart et al. (2004) identified a heterozygous arg675-to-gln (R675Q) substitution in the SCN4A gene. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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<div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0024 NORMOKALEMIC PERIODIC PARALYSIS, POTASSIUM-SENSITIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
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|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, ARG675TRP
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs121908556,
|
|
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|
|
|
gnomAD: rs121908556,
|
|
|
|
|
|
ClinVar: RCV000006263, RCV000206954, RCV000713092, RCV001254163
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with potassium-sensitive normokalemic periodic paralysis (see HYPP, 170500), Vicart et al. (2004) identified a heterozygous arg675-to-trp (R675W) mutation in the SCN4A gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
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|
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<div>
|
|
<br />
|
|
</div>
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|
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</div>
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<div>
|
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0025 MYOTONIA PERMANENS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, GLY1306GLU
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|
|
|
|
|
<br />
|
|
|
|
SNP: rs80338792,
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|
|
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gnomAD: rs80338792,
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|
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|
|
ClinVar: RCV000489251, RCV000552020, RCV001799588, RCV001823093, RCV002225070, RCV002490328, RCV004786240
|
|
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</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a woman with severe myotonia permanens (608390), Lerche et al. (1993) identified a heterozygous c.3917G-A transition in the SCN4A gene, resulting in a gly1306-to-glu (G1306E) substitution in the III-IV linker region of the protein. Patch-clamp recordings on patient muscle samples showed slower sodium fast channel inactivation and an increase in late channel opening, resulting in a steady-state inward current, sustained muscle depolarization, and muscle fiber hyperexcitability. Lerche et al. (1993) identified different pathogenic mutations in the same codon (G1306V; 603967.0007 and G1306A; 603967.0012) in other families with similar disorders, indicating that residue 1306 is important for sodium channel inactivation. </p><p>Colding-Jorgensen et al. (2006) identified a heterozygous G1306E substitution in a father and son with myotonia permanens. The authors noted that the mutation may interfere with the channel voltage sensor. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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<div>
|
|
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0026 PARAMYOTONIA CONGENITA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, MET1476ILE
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|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908559,
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|
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|
|
|
gnomAD: rs121908559,
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|
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|
|
|
ClinVar: RCV000006284, RCV001046179, RCV001781191, RCV003323353
|
|
|
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|
|
</span>
|
|
</div>
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 44 patients from 11 French Canadian families with a myotonia phenotype most consistent with paramyotonia congenita (PMC; 168300), Rossignol et al. (2007) identified a heterozygous 4428G-A transition in the SCN4A gene, resulting in a met1476-to-ile (M1476I) substitution in a highly conserved residue of the domain IV cytoplasmic loop, which is known to be involved in fast inactivation. The patients originated from the Saguenay-Lac-Saint-Jean region with notable clustering around Saint-Felicien. Haplotype analysis indicated a founder effect. The phenotype was quite variable, with age at onset ranging from 5 to 67 years (mean, 21 years) and mild to severe symptoms. Eleven (25%) patients were asymptomatic despite myotonic discharges on EMG. The most consistent features were cold-induced myotonia (41%) and painful myotonia (18%). Potassium challenge was not conducted. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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|
</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0027 PARAMYOTONIA CONGENITA/HYPERKALEMIC PERIODIC PARALYSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, ASN1297LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908560,
|
|
|
|
|
|
|
|
ClinVar: RCV000006285, RCV003996078
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a female infant with severe fatal neonatal nondystrophic myotonia with overlapping features of paramyotonia congenita (PMC; 168300) and hyperkalemic periodic paralysis (HYPP; 170500), Gay et al. (2008) identified a de novo heterozygous 3891C-A transversion in exon 21 of the SCN4A gene, resulting in an asn1297-to-lys (N1297K) substitution in the interdomain loop III-IV. The mutation was not found in either parent or in 100 controls. </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>.0028 PARAMYOTONIA CONGENITA</strong>
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</span>
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</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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SCN4A, ILE693THR
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<br />
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|
SNP: rs80338956,
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ClinVar: RCV000006286, RCV000020266, RCV000485864, RCV002267605
|
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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 6 patients from 4 unrelated European families with paramyotonia congenita (PMC; 168300), Matthews et al. (2008) identified a heterozygous mutation in the SCN4A gene, resulting in an ile693-to-thr (I693T) substitution in the domain II S4-5 cytoplasmic loop. All the patients presented with transient neonatal hypotonia, in some cases requiring feeding or respiratory assistance, and later developed classic PMC by age 5 years. Earlier generations of 3 of the families reported a history of PMC without neonatal hypotonia. The findings expanded the phenotypic spectrum of PMC to include neonatal hypotonia. </p>
|
|
</span>
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|
</div>
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<div>
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<br />
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|
</div>
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</div>
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<div>
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<div>
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|
<h4>
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<span class="mim-font">
|
|
<strong>.0029 PARAMYOTONIA CONGENITA</strong>
|
|
</span>
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|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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SCN4A, ILE141VAL
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<br />
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SNP: rs121908561,
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|
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ClinVar: RCV000006287
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|
|
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|
|
</span>
|
|
</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 a phenotype consistent with paramyotonia congenita (PMC; 168300), Petitprez et al. (2008) identified a heterozygous A-to-G transition in exon 4 of the SCN4A gene, resulting in an ile141-to-val (I141V) substitution in the first transmembrane segment of domain I. The patients had myotonia without muscle weakness. The mutation was not identified in unaffected family members and 100 control individuals. In vitro functional expression studies showed that the mutant protein resulted in a hyperpolarizing shift of the activation curve, with concomitant increase in window current amplitude, suggestive of a gain of function. The studies also showed enhanced slow inactivation, which may have prevented weakness. </p>
|
|
</span>
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|
</div>
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<div>
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|
<br />
|
|
</div>
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|
</div>
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|
<div>
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|
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0030 HYPOKALEMIC PERIODIC PARALYSIS, TYPE 2</strong>
|
|
</span>
|
|
</h4>
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|
</div>
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<div>
|
|
<span class="mim-text-font">
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SCN4A, ARG1132GLN
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<br />
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|
|
SNP: rs80338789,
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|
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|
|
|
gnomAD: rs80338789,
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|
|
ClinVar: RCV000043510, RCV000517960, RCV000692011, RCV001174896
|
|
|
|
|
|
</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a 3-generation family with hypokalemic periodic paralysis type 2 (HOKPP2; 613345), Carle et al. (2006) identified a heterozygous 3395G-A transition in exon 18 of the SCN4A gene, resulting in an arg1132-to-gln (R1132Q) substitution in the voltage sensor S4 of domain III. The mutation, which segregated with the disorder in the family, was not found in 325 control individuals. In vitro functional expression studies in HEK cells showed that the mutation induced a depolarizing shift in the voltage dependence, as well as enhancement of both fast and slow inactivation. These results were consistent with a loss-of-function effect with reduced effectiveness of membrane excitability, resulting in muscle hypoexcitability. Sodium channel conductance was similar to wildtype. </p><p>In Xenopus oocytes, Francis et al. (2011) demonstrated that the R1132Q mutation caused an abnormal gating pore current with a sustained inward sodium flow, consistent with a leaky channel. This current is sufficient to depolarize and render the muscle fiber inexcitable particularly during low external potassium. The findings suggested a mechanism for loss of sarcolemmal excitability during attacks of weakness in HOKPP. In contrast, the R1148C mutation (603967.0003) causing paramyotonia congenita did not result in gating pore abnormalities. </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0031 MYASTHENIC SYNDROME, CONGENITAL, 16</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
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|
SCN4A, SER246LEU
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|
|
<br />
|
|
|
|
SNP: rs80338951,
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|
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|
|
|
|
|
ClinVar: RCV000020280, RCV000201211, RCV000235040
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the ser246-to-leu (S246L) mutation in the SCN4A gene that was found in compound heterozygous state in a patient with congenital myasthenic syndrome-16 (CMS16; 614198) by Tsujino et al. (2003), see 603967.0018. </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0032 MYASTHENIC SYNDROME, CONGENITAL, 16</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, ARG1457HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs863225046,
|
|
|
|
|
|
gnomAD: rs863225046,
|
|
|
|
|
|
ClinVar: RCV000201212, RCV001209122
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 57-year-old woman, born of consanguineous parents, with congenital myasthenic syndrome-16 (CMS16; 614198), Arnold et al. (2015) identified a homozygous c.4370G-A transition (c.4370G-A, NM_000334.4) in exon 24 of the SCN4A gene, resulting in an arg1457-to-his (R1457H) substitution at a conserved residue in the voltage-sensing D4/S4 transmembrane domain. In vitro electrophysiologic studies showed that the mutation caused a 25-mV hyperpolarizing shift in the voltage dependence of inactivation, resulting in enhanced fast inactivation as well as slowed recovery from fast inactivation. In addition, repetitive stimuli elicited markedly weaker current responses. These changes resulted in reduced channel availability, which could explain the patient's muscle weakness. The unaffected parents and sibs were heterozygous for the mutation. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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|
|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0033 VARIANT OF UNKNOWN SIGNIFICANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, GLY1537SER ({dbSNP rs571210585})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs571210585,
|
|
|
|
|
|
gnomAD: rs571210585,
|
|
|
|
|
|
ClinVar: RCV000207488, RCV000551049, RCV004530250, RCV005003560
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant is classified as a variant of unknown significance because its contribution to essential tremor (see, e.g., ETM1, 190300) has not been confirmed.</p><p>In 5 individuals from a Spanish family with variable manifestations of essential tremor, Bergareche et al. (2015) identified a heterozygous c.4609G-A transition in the SCN4A gene, resulting in a gly1537-to-ser (G1537S) substitution at a highly conserved residue in the portion of the IVS5-S6 loop that dips into the membrane and forms the lining of the pore, which is important for ion selectivity. The variant, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the phenotype and was not found in the dbSNP (build 137), 1000 Genomes Project, or Exome Variant Server databases, or in 188 ethnically matched control chromosomes. The authors noted that the variant was subsequently listed in the dbSNP database as rs571210585 and at a low frequency (6.6 x 10(-5)) in the ExAC database. Whole-cell patch-clamp studies indicated that the variant channel had a tendency toward faster activation and significantly faster inactivation at near-threshold potentials compared to wildtype, which may gradually decrease the amplitude in repetitive action potential firing and facilitate oscillations associated with tremor. Monovalent ion selectivity studies showed that the variant channel had increased conductivity for ammonium and potassium, consistent with a gain of function. The phenotype in this family was heterogeneous: the age at onset of postural and/or action tremor ranged from the early twenties to early sixties. Two patients had tremor occurring in the hands and head, 2 had tremor of both hands, which progressed to head tremor in 1 patient and voice tremor in the other, and 1 patient showed only head tremor. In addition, 2 patients had generalized epilepsy with onset at ages 10 and 20 years, respectively. Bergareche et al. (2015) concluded that the SCN4A variant contributed to tremor and increased the susceptibility to epilepsy in this family, and that essential tremor may result from a channelopathy in some cases. The G1537S variant was not detected in 76 sporadic and 25 familial Spanish patients with essential tremor, and other pathogenic SCN4A variants were not found in 22 additional cases with familial essential tremor. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0034 CONGENITAL MYOPATHY 22A, CLASSIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PARAMYOTONIA CONGENITA, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, ARG225TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs764718003,
|
|
|
|
|
|
gnomAD: rs764718003,
|
|
|
|
|
|
ClinVar: RCV001808030, RCV002267640, RCV002464491, RCV003227994, RCV003227995, RCV005023264
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 35-year-old Caucasian woman, born of unrelated parents (family 2), with classic congenital myopathy-22A (CMYO22A; 620351), Zaharieva et al. (2016) identified compound heterozygous mutations in the SCN4A gene: a c.673C-T transition, resulting in an arg225-to-trp (R225W) substitution, and a c.3628G-T transversion, resulting in a cys1209-to-phe (C1209F; 603967.0035) substitution. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Neither variant was present in the ExAC database. Electrophysiologic studies in HEK293 cells transfected with the mutations showed that R225W was a hypomorphic allele causing reduced current amplitude, whereas C1209F resulted in a complete loss of channel function. The patient showed moderate hypotonia at birth requiring early respiratory support, delayed motor milestones, and proximal muscle weakness, but she did not have limb contractures and was ambulatory with a slow waddling gait. Her motor skills improved during childhood, but began to deteriorate around age 30. Her carrier parents were clinically unaffected. </p><p>Zaharieva et al. (2016) noted that Lee et al. (2009) had identified a heterozygous R225W mutation in a 21-year-old Korean man (patient 3) with mild nonpainful paramyotonia congenita (PMC; 168300). R225W is located at the cytoplasmic side of transmembrane S3 segment of domain I. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0035 CONGENITAL MYOPATHY 22A, CLASSIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, CYS1209PHE
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV003227546
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.3628G-T transversion in the SCN4A gene, resulting in a cys1209-to-phe (C1209F) substitution, that was found in compound heterozygous state in a patient with classic congenital myopathy-22A (CMYO22A; 620351), by Zaharieva et al. (2016), see 603967.0034. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0036 CONGENITAL MYOPATHY 22B, SEVERE FETAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, PRO382THR
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV003227547
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 affected sibs from a consanguineous Sudanese family (family 5) with severe fetal congenital myopathy-22B (CMYO22B; 620369), Zaharieva et al. (2016) identified a homozygous c.1144C-A transversion in the SCN4A gene, resulting in a pro382-to-thr (P382T) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The mutation was not present in the ExAC database. Electrophysiologic studies in HEK293 cells transfected with the mutation showed that it resulted in a complete loss of channel function. All 3 patients died prior to delivery or shortly after birth. They had contractures, muscle hypoplasia, and hydrops with pulmonary hypoplasia. The carrier parents were clinically unaffected. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0037 CONGENITAL MYOPATHY 22B, SEVERE FETAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, MET203LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs933258893,
|
|
|
|
|
|
gnomAD: rs933258893,
|
|
|
|
|
|
ClinVar: RCV001387955, RCV003227973
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 sibs, born of unrelated Australian parents (family 6), with severe fetal congenital myopathy-22B (CMYO22B; 620369), Zaharieva et al. (2016) identified compound heterozygous mutations in the SCN4A gene: a c.608T-A transversion, resulting in a met203-to-lys (M203K) substitution, and a c.4779C-A transversion, resulting in a tyr1593-to-ter (Y1593X; 603967.0038) substitution. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Neither mutation was present in the ExAC database. Electrophysiologic studies in HEK293 cells transfected with the M203K mutation showed that it was a hypomorphic allele causing reduced current amplitude; the voltage dependence of activation and fast inactivation was shifted in the depolarizing direction. The Y1593X nonsense mutation was predicted to cause nonsense-mediated mRNA decay and a complete loss of channel function. All patients died in utero or shortly after birth. They had muscle hypoplasia, contractures, and hydrops with pulmonary hypoplasia. The carrier parents were clinically unaffected. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0038 CONGENITAL MYOPATHY 22B, SEVERE FETAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, TYR1593TER
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV003227549
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.4779C-A transversion in the SCN4A gene, resulting in a tyr1593-to-ter (Y1593X) substitution, that was found in compound heterozygous state in 3 sibs with severe fetal congenital myopathy-22B (CMYO22B; 620369) by Zaharieva et al. (2016), see 603967.0037. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0039 CONGENITAL MYOPATHY 22A, CLASSIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN4A, CYS375ARG
|
|
|
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|
<br />
|
|
|
|
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ClinVar: RCV003227550
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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, born of unrelated parents of East Indian descent, with classic congenital myopathy-22A (CMYO22A; 620351), Gonorazky et al. (2017) identified compound heterozygous missense mutations in the SCN4A gene: a c.1123T-C transition (c.1123T-C, NM_000334.4), resulting in a cys375-to-arg (C375R) substitution, and a c.3425G-A transition, resulting in an arg1142-to-gln (R1142Q; 603967.0040) substitution. The mutations, which were found by exome sequencing, segregated with the disorder in the family. In vitro electrophysiologic studies in HEK293 cells showed that the C375R mutation abolished sodium activity and caused a complete loss of SCN4A function, whereas the R1142Q mutation was hypomorphic with reduced peak current densities due to a 4-mV depolarizing shift of activation. Fast inactivation properties of the R1142Q mutant channel were also mildly affected. The patients, who were 21 and 18 years of age, showed hypotonia at birth, proximal muscle weakness of the upper and lower limbs, difficulty walking, and facial muscle weakness. Both also had scaphocephaly due to synostosis of the sagittal and metopic sutures. </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>.0040 CONGENITAL MYOPATHY 22A, CLASSIC</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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SCN4A, ARG1142GLN
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<br />
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SNP: rs780703403,
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gnomAD: rs780703403,
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ClinVar: RCV000557400, RCV003227493, RCV004820047
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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 c.3425G-A transition (c.3425G-A, NM_000334.4) in the SCN4A gene, resulting in an arg1142-to-gln (R1142Q) substitution, that was found in compound heterozygous state in 2 sibs with classic congenital myopathy-22A (CMYO22A; 620351) by Gonorazky et al. (2017), see 603967.0039. </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>.0041 MYASTHENIC SYNDROME, CONGENITAL, 16</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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CONGENITAL MYOPATHY 22A, CLASSIC, 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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SCN4A, ARG1454TRP
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<br />
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SNP: rs879253789,
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gnomAD: rs879253789,
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ClinVar: RCV000235032, RCV001056500, RCV002512068, RCV003227471
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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 />
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<p><strong><em>Congenital Myasthenic Syndrome 16</em></strong></p><p>
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In a 26-year-old Lebanese woman, born of consanguineous parents, with congenital myasthenic syndrome-16 (CMS16; 614198), Habbout et al. (2016) identified a homozygous c.4360C-T transition (c.4360C-T, NM_000334.4) in exon 24 of the SCN4A gene, resulting in an arg1454-to-trp (R1454W) substitution in the DIVS4 domain. Each unaffected parent was heterozygous for the mutation. In vitro functional expression studies showed that the mutation resulted in a loss-of-function effect, with slowed current decay, slowed fast inactivation, and increased activation time compared to wildtype. Slowed inactivation was also disturbed. Current density was not affected, but there was a decrease in current amplitude in response to repetitive stimulation above 10 Hz. The findings thus showed a combination of gating behaviors that favor the inactivation state; defective inactivation may induce fatigable weakness during muscle firing. The phenotype in this patient comprised both CMS and normokalemic periodic paralysis. </p><p><strong><em>Classic Congenital Myopathy 22A</em></strong></p><p>
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For discussion of the c.4360C-T transition in the SCN4A gene, resulting in an R1454W mutation, that was found in compound heterozygous state in a patient with classic congenital myopathy-22A (CMYO22A; 620351) by Berghold et al. (2022), see 603967.0042. Berghold et al. (2022) noted that the R1454W variant was present at a low frequency (1.6 x 10(-5)) in heterozygous state in the gnomAD database. </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>.0042 CONGENITAL MYOPATHY 22A, CLASSIC</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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SCN4A, ASN1205LYS
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<br />
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SNP: rs1181083611,
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gnomAD: rs1181083611,
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ClinVar: RCV001065707, RCV002512136, RCV003227512, RCV004792710
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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 an 18-year-old girl, born of unrelated parents, with classic congenital myopathy-22A (CMYO22A; 620351), Berghold et al. (2022) identified compound heterozygous missense mutations in the SCN4A gene: a c.3615C-G transversion (c.3615C-G, NM_000334.4), resulting in an asn1205-to-lys (N1205K) substitution at a conserved region in domain III, and R1454W (603967.0041). The mutations, which were found by whole-exome sequencing, were inherited from the unaffected parents. R1454W, located in the voltage sensor of domain IV, had been demonstrated to be a loss-of-function variant by Habbout et al. (2016). N1205K, located in a region forming the channel pore, was a novel variant. It was not present in the gnomAD database. Functional studies of N1205K were not performed, but it was predicted to cause a loss of function based on studies of paralogous variants in other SCNA genes. </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>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ackerman, M. J., Clapham, D. E.
|
|
<strong>Ion channels--basic science and clinical disease.</strong>
|
|
New Eng. J. Med. 336: 1575-1586, 1997. Note: Erratum: New Eng. J. Med. 337: 579 only, 1997.
|
|
|
|
|
|
[PubMed: 9164815]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM199705293362207]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Arnold, W. D., Feldman, D. H., Ramirez, S., He, L., Kassar, D., Quick, A., Klassen, T. L., Lara, M., Nguyen, J., Kissel, J. T., Lossin, C., Maselli, R. A.
|
|
<strong>Defective fast inactivation recovery of Na(v)1.4 in congenital myasthenic syndrome.</strong>
|
|
Ann. Neurol. 77: 840-850, 2015.
|
|
|
|
|
|
[PubMed: 25707578]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.24389]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bendahhou, S., Cummins, T. R., Griggs, R. C., Fu, Y.-H., Ptacek, L. J.
|
|
<strong>Sodium channel inactivation defects are associated with acetazolamide-exacerbated hypokalemic periodic paralysis.</strong>
|
|
Ann. Neurol. 50: 417-420, 2001.
|
|
|
|
|
|
[PubMed: 11558801]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.1144]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bennani-Baiti, I. M., Jones, B. K., Liebhaber, S. A., Cooke, N. E.
|
|
<strong>Physical linkage of the human growth hormone gene cluster and the skeletal muscle sodium channel alpha-subunit gene (SCN4A) on chromosome 17.</strong>
|
|
Genomics 29: 647-652, 1995.
|
|
|
|
|
|
[PubMed: 8575757]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1995.9954]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bergareche, A., Bednarz, M. Sanchez, E., Krebs, C. E., Ruiz-Martinez, J., De La Riva, P., Makarov, V., Gorostidi, A., Jurkat-Rott, K., Marti-Masso, J. F., Paisan-Ruiz, C.
|
|
<strong>SCN4A pore mutation pathogenetically contributes to autosomal dominant essential tremor and may increase susceptibility to epilepsy.</strong>
|
|
Hum. Molec. Genet. 24: 7111-7120, 2015.
|
|
|
|
|
|
[PubMed: 26427606]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddv410]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Berghold, V. M., Koko, M., Berutti, R., Plecko, B.
|
|
<strong>Novel SCN4A variant associated with a severe congenital myasthenic syndrome/myopathy phenotype.</strong>
|
|
Front. Pediat. 10: 944784, 2022.
|
|
|
|
|
|
[PubMed: 36090556]
|
|
|
|
|
|
[Full Text: https://doi.org/10.3389/fped.2022.944784]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brancati, F., Valente, E. M., Davies, N. P., Sarkozy, A., Sweeney, M. G., LoMonaco, M., Pizzuti, A., Hanna, M. G., Dallapiccola, B.
|
|
<strong>Severe infantile hyperkalaemic periodic paralysis and paramyotonia congenita: broadening the clinical spectrum associated with the T704M mutation in SCN4A.</strong>
|
|
J. Neurol. Neurosurg. Psychiat. 74: 1339-1341, 2003.
|
|
|
|
|
|
[PubMed: 12933953]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jnnp.74.9.1339]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bulman, D. E., Scoggan, K. A., van Oene, M. D., Nicolle, M. W., Hahn, A. F., Tollar, L. L., Ebers, G. C.
|
|
<strong>A novel sodium channel mutation in a family with hypokalemic periodic paralysis.</strong>
|
|
Neurology 53: 1932-1936, 1999.
|
|
|
|
|
|
[PubMed: 10599760]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.53.9.1932]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cannon, S. C.
|
|
<strong>When all is lost...a severe myopathy with hypotonia from sodium channel mutations.</strong>
|
|
Brain 139: 642-644, 2016.
|
|
|
|
|
|
[PubMed: 26917582]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/awv400]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Carle, T., Lhuillier, L., Luce, S., Sternberg, D., Devuyst, O., Fontaine, B., Tabti, N.
|
|
<strong>Gating defects of a novel Na+ channel mutant causing hypokalemic periodic paralysis.</strong>
|
|
Biochem. Biophys. Res. Commun. 348: 653-661, 2006.
|
|
|
|
|
|
[PubMed: 16890191]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.bbrc.2006.07.101]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Colding-Jorgensen, E., Duno, M., Vissing, J.
|
|
<strong>Autosomal dominant monosymptomatic myotonia permanens.</strong>
|
|
Neurology 67: 153-155, 2006.
|
|
|
|
|
|
[PubMed: 16832098]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000223838.88872.da]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Davies, N. P., Eunson, L. H., Gregory, R. P., Mills, K. R., Morrison, P. J., Hanna, M. G.
|
|
<strong>Clinical, electrophysiological, and molecular genetic studies in a new family with paramyotonia congenita.</strong>
|
|
J. Neurol. Neurosurg. Psychiat. 68: 504-507, 2000. Note: Erratum: J. Neurol. Neurosurg. Psychiat. 69: 139 only, 2000.
|
|
|
|
|
|
[PubMed: 10727489]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jnnp.68.4.504]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Davies, N. P., Eunson, L. H., Samuel, M., Hanna, M. G.
|
|
<strong>Sodium channel gene mutations in hypokalemic periodic paralysis: an uncommon cause in the UK.</strong>
|
|
Neurology 57: 1323-1325, 2001.
|
|
|
|
|
|
[PubMed: 11591859]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.57.7.1323]
|
|
|
|
|
|
</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">
|
|
Feero, W. G., Wang, J., Barany, F., Zhou, J., Todorovic, S. M., Conwit, R., Galloway, G., Hausmanowa-Petrusewicz, I., Fidzianska, A., Arahata, K., Wessel, H. B., Wadelius, C., Marks, H. G., Hartlage, P., Hayakawa, H., Hoffman, E. P.
|
|
<strong>Hyperkalemic periodic paralysis: rapid molecular diagnosis and relationship of genotype to phenotype in 12 families.</strong>
|
|
Neurology 43: 668-673, 1993.
|
|
|
|
|
|
[PubMed: 8385748]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.43.4.668]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fontaine, B., Khurana, T. S., Hoffman, E. P., Bruns, G. A. P., Haines, J. L., Trofatter, J. A., Hanson, M. P., Rich, J., McFarlane, H., Yasek, D. M., Romano, D., Gusella, J. F., Brown, R. H., Jr.
|
|
<strong>Hyperkalemic periodic paralysis and the adult muscle sodium channel alpha-subunit gene.</strong>
|
|
Science 250: 1000-1002, 1990.
|
|
|
|
|
|
[PubMed: 2173143]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.2173143]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Francis, D. G., Rybalchenko, V., Struyk, A., Cannon, S. C.
|
|
<strong>Leaky sodium channels from voltage sensor mutations in periodic paralysis, but not paramyotonia.</strong>
|
|
Neurology 76: 1635-1641, 2011.
|
|
|
|
|
|
[PubMed: 21490317]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/WNL.0b013e318219fb57]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gay, S., Dupuis, D., Faivre, L., Masurel-Paulet, A., Labenne, M., Colombani, M., Soichot, P., Huet, F., Hainque, B., Sternberg, D., Fontaine, B., Gouyon, J.-B., Thauvin-Robinet, C.
|
|
<strong>Severe neonatal non-dystrophic myotonia secondary to a novel mutation of the voltage-gated sodium channel (SCN4A) gene.</strong>
|
|
Am. J. Med. Genet. 146A: 380-383, 2008.
|
|
|
|
|
|
[PubMed: 18203179]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.32141]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
George, A. L., Jr., Iyer, G. S., Kleinfield, R., Kallen, R. G., Barchi, R. L.
|
|
<strong>Genomic organization of the human skeletal muscle sodium channel gene.</strong>
|
|
Genomics 15: 598-606, 1993.
|
|
|
|
|
|
[PubMed: 8385647]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1993.1113]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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George, A. L., Jr., Komisarof, J., Kallen, R. G., Barchi, R. L.
|
|
<strong>Primary structure of the adult human skeletal muscle voltage-dependent sodium channel.</strong>
|
|
Ann. Neurol. 31: 131-137, 1992.
|
|
|
|
|
|
[PubMed: 1315496]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.410310203]
|
|
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|
|
|
</p>
|
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</li>
|
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
George, A. L., Jr., Ledbetter, D. H., Kallen, R. G., Barchi, R. L.
|
|
<strong>Assignment of a human skeletal muscle sodium channel alpha-subunit gene (SCN4A) to 17q23.1-25.3.</strong>
|
|
Genomics 9: 555-556, 1991.
|
|
|
|
|
|
[PubMed: 1851726]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(91)90425-e]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gonorazky, H. D., Marshall, C. R., Al-Murshed, M., Hazrati, L. N., Thor, M. G., Hanna, M. G., Mannikko, R., Ray, P. N., Yoon, G.
|
|
<strong>Congenital myopathy with "corona" fibres, selective muscle atrophy, and craniosynostosis associated with novel recessive mutations in SCN4A.</strong>
|
|
Neuromusc. Disord. 27: 574-580, 2017.
|
|
|
|
|
|
[PubMed: 28262468]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.nmd.2017.02.001]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Habbout, K., Poulin, H., Rivier, F., Giuliano, S., Sternberg, D., Fontaine, B., Eymard, B., Morales, R. J., Echenne, B., King, L., Hanna, M. G., Mannikko, R., Chahine, M., Nicole, S., Bendahhou, S.
|
|
<strong>A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with periodic paralysis.</strong>
|
|
Neurology 86: 161-169, 2016.
|
|
|
|
|
|
[PubMed: 26659129]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/WNL.0000000000002264]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hayward, L. J., Kim, J. S., Lee, M.-Y., Zhou, H., Kim, J. W., Misra, K., Salajegheh, M., Wu, F., Matsuda, C., Reid, V., Cros, D., Hoffman, E. P., Renaud, J.-M., Cannon, S. C., Brown, R. H., Jr.
|
|
<strong>Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and potassium-sensitive weakness.</strong>
|
|
J. Clin. Invest. 118: 1437-1449, 2008.
|
|
|
|
|
|
[PubMed: 18317596]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI32638]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Heine, R., Pika, U., Lehmann-Horn, F.
|
|
<strong>A novel SCN4A mutation causing myotonia aggravated by cold and potassium.</strong>
|
|
Hum. Molec. Genet. 2: 1349-1353, 1993.
|
|
|
|
|
|
[PubMed: 8242056]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/2.9.1349]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hisama, F. M.
|
|
<strong>Familial periodic paralysis and Charcot-Marie-Tooth disease in a 7-generation family.</strong>
|
|
Arch. Neurol. 62: 135-138, 2005.
|
|
|
|
|
|
[PubMed: 15642860]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archneur.62.1.135]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Iaizzo, P. A., Franke, C., Hatt, H., Spittelmeister, W., Ricker, K., Rudel, R., Lehmann-Horn, F.
|
|
<strong>Altered sodium channel behaviour causes myotonia in autosomal dominantly inherited myotonia congenita.</strong>
|
|
Neuromusc. Disord. 1: 47-53, 1991.
|
|
|
|
|
|
[PubMed: 1668369]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0960-8966(91)90042-q]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jurkat-Rott, K., Mitrovic, N., Hang, C., Kouzmekine, A., Iaizzo, P., Herzog, J., Lerche, H., Nicole, S., Vale-Santos, J., Chauveau, D., Fontaine, B., Lehmann-Horn, F.
|
|
<strong>Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current.</strong>
|
|
Proc. Nat. Acad. Sci. 97: 9549-9554, 2000.
|
|
|
|
|
|
[PubMed: 10944223]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.97.17.9549]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kelly, P., Yang, W. S., Costigan, D., Farrell, M. A., Murphy, S., Hardiman, O.
|
|
<strong>Paramyotonia congenita and hyperkalemic periodic paralysis associated with a met1592-to-val substitution in the skeletal muscle sodium channel alpha subunit--a large kindred with a novel phenotype.</strong>
|
|
Neuromusc. Disord. 7: 105-111, 1997.
|
|
|
|
|
|
[PubMed: 9131651]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0960-8966(96)00429-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kim, J., Hahn, Y., Sohn, E. H., Lee, Y. J., Yun, J. H., Kim, J. M., Chung, J. H.
|
|
<strong>Phenotypic variation of a thr704met mutation in skeletal sodium channel gene in a family with paralysis periodica paramyotonica.</strong>
|
|
J. Neurol. Neurosurg. Psychiat. 70: 618-623, 2001.
|
|
|
|
|
|
[PubMed: 11309455]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jnnp.70.5.618]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koch, M. C., Baumbach, K., George, A. L., Ricker, K.
|
|
<strong>Paramyotonia congenita without paralysis on exposure to cold: a novel mutation in the SCN4A gene (val1293ile).</strong>
|
|
Neuroreport 6: 2001-2004, 1995.
|
|
|
|
|
|
[PubMed: 8580427]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/00001756-199510010-00012]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kuzmenkin, A., Muncan, V., Jurkat-Rott, K., Hang, C., Lerche, H., Lehmann-Horn, F., Mitrovic, N.
|
|
<strong>Enhanced inactivation and pH sensitivity of Na+ channel mutations causing hypokalemic periodic paralysis type II.</strong>
|
|
Brain 125: 835-843, 2002.
|
|
|
|
|
|
[PubMed: 11912116]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/awf071]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lee, S. C., Kim, H. S., Park, Y. E., Choi, Y. C., Park, K. H., Kim, D. S.
|
|
<strong>Clinical diversity of SCN4A-mutation-associated skeletal muscle sodium channelopathy.</strong>
|
|
J. Clin. Neurol. 5: 186-191, 2009.
|
|
|
|
|
|
[PubMed: 20076800]
|
|
|
|
|
|
[Full Text: https://doi.org/10.3988/jcn.2009.5.4.186]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lerche, H., Heine, R., Pika, U., George, A. L., Jr., Mitrovic, N., Browatzki, M., Weiss, T., Rivet-Bastide, M., Franke, C., Lomonaco, M., Ricker, K., Lehmann-Horn, F.
|
|
<strong>Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III-IV linker.</strong>
|
|
J. Physiol. 470: 13-22, 1993.
|
|
|
|
|
|
[PubMed: 8308722]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1113/jphysiol.1993.sp019843]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matthews, E., Guet, A., Mayer, M., Vicart, S., Pemble, S., Sternberg, D., Fontaine, B., Hanna, M. G.
|
|
<strong>Neonatal hypotonia can be a sodium channelopathy: recognition of a new phenotype.</strong>
|
|
Neurology 71: 1740-1742, 2008.
|
|
|
|
|
|
[PubMed: 19015492]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000335269.21550.0e]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matthews, E., Labrum, R., Sweeney, M. G., Sud, R., Haworth, A., Chinnery, P. F., Meola, G., Schorge, S., Kullmann, D. M., Davis, M. B., Hanna, M. G.
|
|
<strong>Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis.</strong>
|
|
Neurology 72: 1544-1547, 2009.
|
|
|
|
|
|
[PubMed: 19118277]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000342387.65477.46]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matthews, E., Manzur, A. Y., Sud, R., Muntoni, F., Hanna, M. G.
|
|
<strong>Stridor as a neonatal presentation of skeletal muscle sodium channelopathy.</strong>
|
|
Arch. Neurol. 68: 127-129, 2011.
|
|
|
|
|
|
[PubMed: 21220685]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archneurol.2010.347]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McClatchey, A. I., Lin, C. S., Wang, J., Hoffman, E. P., Rojas, C., Gusella, J. F.
|
|
<strong>The genomic structure of the human skeletal muscle sodium channel gene.</strong>
|
|
Hum. Molec. Genet. 1: 521-527, 1992.
|
|
|
|
|
|
[PubMed: 1339144]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/1.7.521]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McClatchey, A. I., McKenna-Yasek, D., Cros, D., Worthen, H. G., Kuncl, R. W., DeSilva, S. M., Cornblath, D. R., Gusella, J. F., Brown, R. H., Jr.
|
|
<strong>Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel.</strong>
|
|
Nature Genet. 2: 148-152, 1992.
|
|
|
|
|
|
[PubMed: 1338909]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1092-148]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McClatchey, A. I., Van den Bergh, P., Pericak-Vance, M. A., Raskind, W., Verellen, C., McKenna-Yasek, D., Rao, K., Haines, J. L., Bird, T., Brown, R. H., Jr., Gusella, J. F.
|
|
<strong>Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita.</strong>
|
|
Cell 68: 769-774, 1992.
|
|
|
|
|
|
[PubMed: 1310898]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(92)90151-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Meyer-Kleine, C., Otto, M., Zoll, B., Koch, M. C.
|
|
<strong>Molecular and genetic characterization of German families with paramyotonia congenita and demonstration of founder effect in the Ravensberg families.</strong>
|
|
Hum. Genet. 93: 707-710, 1994.
|
|
|
|
|
|
[PubMed: 8005599]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00201577]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Miller, T. M., Dias da Silva, M. R., Miller, H. A., Kwiecinski, H., Mendell, J. R., Tawil, R., McManis, P., Griggs, R. C., Angelini, C., Servidei, S., Petajan, J., Dalakas, M. C., Ranum, L. P. W., Fu, Y. H., Ptacek, L. J.
|
|
<strong>Correlating phenotype and genotype in the periodic paralyses.</strong>
|
|
Neurology 63: 1647-1655, 2004.
|
|
|
|
|
|
[PubMed: 15534250]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000143383.91137.00]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Orrell, R. W., Jurkat-Rott, K., Lehmann-Horn, F., Lane, R. J. M.
|
|
<strong>Familial cramp due to potassium-aggravated myotonia.</strong>
|
|
J. Neurol. Neurosurg. Psychiat. 65: 569-572, 1998.
|
|
|
|
|
|
[PubMed: 9771789]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jnnp.65.4.569]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Petitprez, S., Tiab, L., Chen, L., Kappeler, L., Rosler, K. M., Schorderet, D., Abriel, H., Burgunder, J.-M.
|
|
<strong>A novel dominant mutation of the Na(v)1.4 alpha-subunit domain I leading to sodium channel myotonia.</strong>
|
|
Neurology 71: 1669-1675, 2008.
|
|
|
|
|
|
[PubMed: 19015483]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000335168.86248.55]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ptacek, L. J., George, A. L., Jr., Barchi, R. L., Griggs, R. C., Riggs, J. E., Robertson, M., Leppert, M. F.
|
|
<strong>Mutations in an S4 segment of the adult skeletal muscle sodium channel cause paramyotonia congenita.</strong>
|
|
Neuron 8: 891-897, 1992.
|
|
|
|
|
|
[PubMed: 1316765]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0896-6273(92)90203-p]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ptacek, L. J., George, A. L., Jr., Griggs, R. C., Tawil, R., Kallen, R. G., Barchi, R. L., Robertson, M., Leppert, M. F.
|
|
<strong>Identification of a mutation in the gene causing hyperkalemic periodic paralysis.</strong>
|
|
Cell 67: 1021-1027, 1991.
|
|
|
|
|
|
[PubMed: 1659948]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(91)90374-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ptacek, L. J., Gouw, L., Kwiencinski, H., McManis, P., Mendell, J. R., Barohn, A. L., Jr., Robertson, M., Leppert, M. F.
|
|
<strong>Sodium channel mutations in paramyotonia congenita and hyperkalemic periodic paralysis.</strong>
|
|
Ann. Neurol. 33: 300-307, 1993.
|
|
|
|
|
|
[PubMed: 8388676]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.410330312]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ptacek, L. J., Tawil, R., Griggs, R. C., Meola, G., McManis, P., Barohn, R. J., Mendell, J. R., Harris, C., Spitzer, R., Santiago, F., Leppert, M. F.
|
|
<strong>Sodium channel mutations in acetazolamide-responsive myotonia congenita, paramyotonia congenita, and hyperkalemic periodic paralysis.</strong>
|
|
Neurology 44: 1500-1503, 1994.
|
|
|
|
|
|
[PubMed: 8058156]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.44.8.1500]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ricker, K., Moxley, R. T., III, Heine, R., Lehmann-Horn, F.
|
|
<strong>Myotonia fluctuans: a third type of muscle sodium channel disease.</strong>
|
|
Arch. Neurol. 51: 1095-1102, 1994.
|
|
|
|
|
|
[PubMed: 7980103]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archneur.1994.00540230033009]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rojas, C. V., Wang, J., Schwartz, L. S., Hoffman, E. P., Powell, B. R., Brown, R. H., Jr.
|
|
<strong>A met-to-val mutation in the skeletal muscle Na+ channel alpha-subunit in hyperkalaemic periodic paralysis.</strong>
|
|
Nature 354: 387-389, 1991.
|
|
|
|
|
|
[PubMed: 1659668]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/354387a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rojas, C. V.
|
|
<strong>Personal Communication.</strong>
|
|
Pittsburgh, Pa. 2/6/1992.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rosenfeld, J., Sloan-Brown, K., George, A. L., Jr.
|
|
<strong>A novel muscle sodium channel mutation causes painful congenital myotonia.</strong>
|
|
Ann. Neurol. 42: 811-814, 1997.
|
|
|
|
|
|
[PubMed: 9392583]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.410420520]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rossignol, E., Mathieu, J., Thiffault, I., Tetreault, M., Dicaire, M.-J., Chrestian, N., Dupre, N., Puymirat, J., Brais, B.
|
|
<strong>A novel founder SCN4A mutation causes painful cold-induced myotonia in French-Canadians.</strong>
|
|
Neurology 69: 1937-1941, 2007.
|
|
|
|
|
|
[PubMed: 17998485]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000290831.08585.2c]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rudolph, J. A., Spier, S. J., Byrns, G., Hoffman, E. P.
|
|
<strong>Linkage of hyperkalaemic periodic paralysis in Quarter horses to the horse adult skeletal muscle sodium channel gene.</strong>
|
|
Anim. Genet. 23: 241-250, 1992.
|
|
|
|
|
|
[PubMed: 1323940]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2052.1992.tb00136.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rudolph, J. A., Spier, S. J., Byrns, G., Rojas, C. V., Bernoco, D., Hoffman, E. P.
|
|
<strong>Periodic paralysis in Quarter horses: a sodium channel mutation disseminated by selective breeding.</strong>
|
|
Nature Genet. 2: 144-147, 1992.
|
|
|
|
|
|
[PubMed: 1338908]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1092-144]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sasaki, R., Takano, H., Kamakura, K., Kaida, K., Hirata, A., Saito, M., Tanaka, H., Kuzuhara, S., Tsuji, S.
|
|
<strong>A novel mutation in the gene for the adult skeletal muscle sodium channel alpha-subunit (SCN4A) that causes paramyotonia congenita of von Eulenburg.</strong>
|
|
Arch. Neurol. 56: 692-696, 1999.
|
|
|
|
|
|
[PubMed: 10369308]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archneur.56.6.692]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sillen, A., Wadelius, C., Sundvall, M., Ahlsten, G., Gustavson, K. H.
|
|
<strong>Hyperkalemic periodic paralysis caused by recurring mutation in the adult muscle sodium channel alpha-subunit gene.</strong>
|
|
Genet. Counsel. 7: 267-275, 1996.
|
|
|
|
|
|
[PubMed: 8985730]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sokolov, S., Scheuer, T., Catterall, W. A.
|
|
<strong>Gating pore current in an inherited ion channelopathy.</strong>
|
|
Nature 446: 76-78, 2007.
|
|
|
|
|
|
[PubMed: 17330043]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature05598]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sugiura, Y., Aoki, T., Sugiyama, Y., Hida, C., Ogata, M., Yamamoto, T.
|
|
<strong>Temperature-sensitive sodium channelopathy with heat-induced myotonia and cold-induced paralysis.</strong>
|
|
Neurology 54: 2179-2181, 2000.
|
|
|
|
|
|
[PubMed: 10851391]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.54.11.2179]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sugiura, Y., Makita, N., Li, L., Noble, P. J., Kimura, J., Kumagai, Y., Soeda, T., Yamamoto, T.
|
|
<strong>Cold induces shifts of voltage dependence in mutant SCN4A, causing hypokalemic periodic paralysis.</strong>
|
|
Neurology 61: 914-918, 2003.
|
|
|
|
|
|
[PubMed: 14557559]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000086820.54065.a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tahmoush, A. J., Schaller, K. L., Zhang, P., Hyslop, T., Heiman-Patterson, T., Caldwell, J. H.
|
|
<strong>Muscle sodium channel inactivation defect in paramyotonia congenita with the thr1313-to-met mutation.</strong>
|
|
Neuromusc. Disord. 4: 447-454, 1994.
|
|
|
|
|
|
[PubMed: 7533571]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0960-8966(94)90083-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tsujino, A., Maertens, C., Ohno, K., Shen, X.-M., Fukuda, T., Harper, C. M., Cannon, S. C., Engel, A. G.
|
|
<strong>Myasthenic syndrome caused by mutation of the SCN4A sodium channel.</strong>
|
|
Proc. Nat. Acad. Sci. 100: 7377-7382, 2003.
|
|
|
|
|
|
[PubMed: 12766226]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.1230273100]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Venance, S. L., Jurkat-Rott, K., Lehmann-Horn, F., Tawil, R.
|
|
<strong>SCN4A-associated hypokalemic periodic paralysis merits a trial of acetazolamide.</strong>
|
|
Neurology 63: 1977 only, 2004.
|
|
|
|
|
|
[PubMed: 15557532]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000143068.99794.5b]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vicart, S., Sternberg, D., Fournier, E., Ochsner, F., Laforet, P., Kuntzer, T., Eymard, B., Hainque, B., Fontaine, B.
|
|
<strong>New mutations of SCN4A cause a potassium-sensitive normokalemic periodic paralysis.</strong>
|
|
Neurology 63: 2120-2127, 2004.
|
|
|
|
|
|
[PubMed: 15596759]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000145768.09934.ec]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, D. W., VanDeCarr, D., Ruben, P. C., George, A. L., Jr., Bennett, P. B.
|
|
<strong>Functional consequences of a domain 1/S6 segment sodium channel mutation associated with painful congenital myotonia.</strong>
|
|
FEBS Lett. 448: 231-234, 1999.
|
|
|
|
|
|
[PubMed: 10218481]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0014-5793(99)00338-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, J., Rojas, C. V., Zhou, J., Schwartz, L. S., Nicholas, H., Hoffman, E. P.
|
|
<strong>Sequence and genomics structure of the human adult skeletal muscle sodium channel alpha subunit gene on 17q.</strong>
|
|
Biochem. Biophys. Res. Commun. 182: 794-801, 1992.
|
|
|
|
|
|
[PubMed: 1310396]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0006-291x(92)91802-w]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wu, F., Mi, W., Fu, Y., Struyk, A., Cannon, S. C.
|
|
<strong>Mice with an NaV1.4 sodium channel null allele have latent myasthenia, without susceptibility to periodic paralysis.</strong>
|
|
Brain 139: 1688-1699, 2016.
|
|
|
|
|
|
[PubMed: 27048647]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/aww070]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yamada, T., Ochi, H., Hara, H., Yoshimura, T., Kobayashi T.
|
|
<strong>A skeletal muscle sodium channel mutation in a Japanese family with paramyotonia congenita.</strong>
|
|
J. Neurol. Sci. 133: 192-193, 1995.
|
|
|
|
|
|
[PubMed: 8583225]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0022-510x(95)00166-y]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
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<li>
|
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Zaharieva, I. T., Thor, M. G., Oates, E. C., van Karnebeek, C., Hendson, G., Blom, E., Witting, N., Rasmussen, M., Gabbett, M. T., Ravenscroft, G., Sframeli, M., Suetterlin, K., and 28 others.
|
|
<strong>Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy.</strong>
|
|
Brain 139: 674-691, 2016.
|
|
|
|
|
|
[PubMed: 26700687]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/awv352]
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Cassandra L. Kniffin - updated : 05/05/2023<br>Cassandra L. Kniffin - updated : 04/28/2023<br>Cassandra L. Kniffin - updated : 2/11/2016<br>Cassandra L. Kniffin - updated : 10/15/2015<br>Cassandra L. Kniffin - updated : 5/8/2013<br>Cassandra L. Kniffin - updated : 4/18/2011<br>Cassandra L. Kniffin - updated : 3/11/2010<br>Cassandra L. Kniffin - updated : 10/27/2009<br>Cassandra L. Kniffin - updated : 4/6/2009<br>Cassandra L. Kniffin - updated : 10/24/2008<br>Patricia A. Hartz - updated : 7/22/2008<br>Marla J. F. O'Neill - updated : 4/24/2008<br>Cassandra L. Kniffin - updated : 3/31/2008<br>Cassandra L. Kniffin - updated : 6/29/2007<br>Ada Hamosh - updated : 6/20/2007<br>Cassandra L. Kniffin - updated : 7/12/2005<br>Cassandra L. Kniffin - updated : 5/9/2005<br>Cassandra L. Kniffin - updated : 3/16/2005<br>Cassandra L. Kniffin - updated : 1/27/2005<br>Cassandra L. Kniffin - reorganized : 1/28/2004<br>Victor A. McKusick - updated : 7/14/2003<br>Victor A. McKusick - updated : 9/26/2000
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