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Entry
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- *602235 - POTASSIUM CHANNEL, VOLTAGE-GATED, KQT-LIKE SUBFAMILY, MEMBER 2; KCNQ2
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<p>
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<span class="h4">*602235</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="#geneFunction">Gene Function</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/602235">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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</li>
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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 panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000075043;t=ENST00000359125" 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=3785" 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=602235" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000075043;t=ENST00000359125" 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_001382235,NM_004518,NM_172106,NM_172107,NM_172108,NM_172109,XM_011528811,XM_017027841,XM_017027842,XM_017027843,XM_017027844,XM_017027845,XM_047440144,XM_047440145" 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_172107" 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=602235" 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=03757&isoform_id=03757_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/KCNQ2" 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/1841342,2801452,2826773,3294577,4324687,12653821,14285389,26051260,26051262,26051264,26051266,26051268,30582925,37181490,119595677,119595678,119595679,119595680,119595681,119595682,119595683,119595684,119595685,119595686,119595687,119595688,194374519,768017134,1034625106,1034625108,1034625110,1034625112,1034625114,1834377655,2217335148,2217335153,2228639043,2462580331,2462580333,2462580335,2462580337,2462580339,2462580341,2462580343,2462580345" 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/O43526" 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=3785" 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=ENSG00000075043;t=ENST00000359125" 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=KCNQ2" 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=KCNQ2" 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+3785" 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/KCNQ2" 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:3785" 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/3785" 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=chr20&hgg_gene=ENST00000359125.7&hgg_start=63400208&hgg_end=63472655&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:6296" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:6296" 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/kcnq2" 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=602235[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=602235[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/KCNQ2/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/ENSG00000075043" 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=KCNQ2" 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=KCNQ2" 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=KCNQ2" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=KCNQ2&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/PA30074" 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:6296" 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/FBgn0033494.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:1309503" 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/KCNQ2#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:1309503" 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/3785/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=3785" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00002233;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-080220-37" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:3785" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=KCNQ2&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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602235
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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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POTASSIUM CHANNEL, VOLTAGE-GATED, KQT-LIKE SUBFAMILY, MEMBER 2; KCNQ2
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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">
|
|
POTASSIUM CHANNEL, VOLTAGE-GATED, SUBFAMILY Q, MEMBER 2
|
|
</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>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=KCNQ2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">KCNQ2</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/20/471?start=-3&limit=10&highlight=471">20q13.33</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr20:63400208-63472655&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'})">20:63,400,208-63,472,655</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>
|
|
<br />
|
|
</div>
|
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<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=613720,121200,121200" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/20/471?start=-3&limit=10&highlight=471">
|
|
20q13.33
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Developmental and epileptic encephalopathy 7
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/613720"> 613720 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
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|
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</span>
|
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</td>
|
|
<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>
|
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<span class="mim-font">
|
|
Myokymia
|
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|
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</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/121200"> 121200 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
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<p>The KCNQ2 gene encodes a voltage-gated potassium channel that is expressed in the brain (<a href="#3" class="mim-tip-reference" title="Biervert, C., Schroeder, B. C., Kubisch, C., Berkovic, S. F., Propping, P., Jentsch, T. J., Steinlein, O. K. <strong>A potassium channel mutation in neonatal human epilepsy.</strong> Science 279: 403-406, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9430594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9430594</a>] [<a href="https://doi.org/10.1126/science.279.5349.403" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9430594">Biervert et al., 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9430594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In the course of a search for the mutational basis of benign familial neonatal seizures (BFNS1; <a href="/entry/121200">121200</a>) mapping to chromosome 20, <a href="#14" class="mim-tip-reference" title="Singh, N. A., Charlier, C., Stauffer, D., DuPont, B. R., Leach, R. J., Melis, R., Ronen, G. M., Bjerre, I., Quattlebaum, T., Murphy, J. V., McHarg, M. L., Gagnon, D., Rosales, T. O., Peiffer, A., Anderson, V. E., Leppert, M. <strong>A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns.</strong> Nature Genet. 18: 25-29, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9425895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9425895</a>] [<a href="https://doi.org/10.1038/ng0198-25" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9425895">Singh et al. (1998)</a> identified a novel voltage-gated potassium channel gene that showed significant homology to KVLQT1 (also known as KCNQ1 and KCNA9), the chromosome 11 potassium channel gene responsible for long QT syndrome-1 (<a href="/entry/192500">192500</a>) and a form of Jervell and Lange-Nielsen cardioauditory syndrome (<a href="/entry/220400">220400</a>). A single cDNA isolated with the D20S24 probe in this region showed significant homology with KVLQT1. <a href="#14" class="mim-tip-reference" title="Singh, N. A., Charlier, C., Stauffer, D., DuPont, B. R., Leach, R. J., Melis, R., Ronen, G. M., Bjerre, I., Quattlebaum, T., Murphy, J. V., McHarg, M. L., Gagnon, D., Rosales, T. O., Peiffer, A., Anderson, V. E., Leppert, M. <strong>A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns.</strong> Nature Genet. 18: 25-29, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9425895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9425895</a>] [<a href="https://doi.org/10.1038/ng0198-25" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9425895">Singh et al. (1998)</a> found that the KCNQ2 cDNA hybridized to transcripts of approximately 1.5, 3.8, and 9.5 kb on Northern blots made from brain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9425895" 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 positional cloning from the 20q13.3 region where 1 form of benign familial neonatal seizures is known to map, <a href="#3" class="mim-tip-reference" title="Biervert, C., Schroeder, B. C., Kubisch, C., Berkovic, S. F., Propping, P., Jentsch, T. J., Steinlein, O. K. <strong>A potassium channel mutation in neonatal human epilepsy.</strong> Science 279: 403-406, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9430594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9430594</a>] [<a href="https://doi.org/10.1126/science.279.5349.403" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9430594">Biervert et al. (1998)</a> independently isolated the KCNQ2 gene and found that it was expressed in brain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9430594" 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="Yang, W.-P., Levesque, P. C., Little, W. A., Conder, M. L., Ramakrishnan, P., Neubauer, M. G., Blanar, M. A. <strong>Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy.</strong> J. Biol. Chem. 273: 19419-19423, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9677360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9677360</a>] [<a href="https://doi.org/10.1074/jbc.273.31.19419" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9677360">Yang et al. (1998)</a> described the cloning, tissue distribution, and functional expression of KCNQ2 and KCNQ3 (<a href="/entry/602232">602232</a>), both of which are associated with benign neonatal epilepsy. The deduced 871-amino acid KCNQ2 protein has features of a voltage-gated potassium channel. Northern blot analysis of 8 human tissues detected an 8.5-kb KCNQ2 transcript in brain only. Within brain, highest expression of KCNQ2 was detected in cerebellar cortex, amygdala, caudate nucleus, and hippocampus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9677360" 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="#4" class="mim-tip-reference" title="Biervert, C., Steinlein, O. K. <strong>Structural and mutational analysis of KCNQ2, the major gene locus for benign familial neonatal convulsions.</strong> Hum. Genet. 104: 234-240, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10323247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10323247</a>] [<a href="https://doi.org/10.1007/pl00008713" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10323247">Biervert and Steinlein (1999)</a> determined that the KCNQ2 gene has at least 18 exons, occupying more than 50 kb of genomic DNA. Splice variants were identified. For example, in fetal brain, exon 8 was absent in all transcripts, while this exon was present in clones derived from adult brain RNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10323247" 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="#3" class="mim-tip-reference" title="Biervert, C., Schroeder, B. C., Kubisch, C., Berkovic, S. F., Propping, P., Jentsch, T. J., Steinlein, O. K. <strong>A potassium channel mutation in neonatal human epilepsy.</strong> Science 279: 403-406, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9430594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9430594</a>] [<a href="https://doi.org/10.1126/science.279.5349.403" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9430594">Biervert et al. (1998)</a> found that expression of human KCNQ2 in Xenopus laevis oocytes led to potassium-selective currents that activated slowly with depolarization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9430594" 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>The M channel is a slowly activating and deactivating potassium conductance that plays a critical role in determining the subthreshold electroexcitability of neurons as well as the responsiveness to synaptic inputs. The M current was first described in peripheral sympathetic neurons, and differential expression of this conductance produces subtypes of sympathetic neurons with distinct firing patterns. The M channel is also expressed in many neurons in the central nervous system. <a href="#15" class="mim-tip-reference" title="Wang, H.-S., Pan, Z., Shi, W., Brown, B. S., Wymore, R. S., Cohen, I. S., Dixon, J. E., McKinnon, D. <strong>KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel.</strong> Science 282: 1890-1893, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9836639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9836639</a>] [<a href="https://doi.org/10.1126/science.282.5395.1890" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9836639">Wang et al. (1998)</a> showed that the KCNQ2 and KCNQ3 channel subunits can coassemble to form a channel with essentially identical biophysical properties and pharmacologic sensitivities to the native M channel and that the pattern of KCNQ2 and KCNQ3 gene expression is consistent with these genes encoding the native M channel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9836639" 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="Yang, W.-P., Levesque, P. C., Little, W. A., Conder, M. L., Ramakrishnan, P., Neubauer, M. G., Blanar, M. A. <strong>Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy.</strong> J. Biol. Chem. 273: 19419-19423, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9677360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9677360</a>] [<a href="https://doi.org/10.1074/jbc.273.31.19419" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9677360">Yang et al. (1998)</a> demonstrated that KCNQ2 and KCNQ3, both of which are associated with benign neonatal epilepsy, interact functionally with each other and with KCNE1 (<a href="/entry/176261">176261</a>), which is mutant in a form of Jervell and Lange-Nielsen syndrome and in 1 form of long QT syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9677360" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Cooper, E. C., Aldape, K. D., Abosch, A., Barbaro, N. M., Berger, M. S., Peacock, W. S., Jan, Y. N., Jan, L. Y. <strong>Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy.</strong> Proc. Nat. Acad. Sci. 97: 4914-4919, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10781098/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10781098</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10781098[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.090092797" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10781098">Cooper et al. (2000)</a> provided information regarding the in vivo distribution and biochemical characteristics of human brain KCNQ2 and KCNQ3, the 2 channel subunits that form M channels when expressed in vitro, and, when mutated, cause the dominantly inherited epileptic syndrome, benign familial neonatal seizures. They found that the KCNQ2 and KCNQ3 proteins are colocalized in a somatodendritic pattern on pyramidal and polymorphic neurons in the human cortex and hippocampus. Immunoreactivity for KCNQ2, but not KCNQ3, is also prominent in some terminal fields, suggesting a presynaptic role for a distinct subgroup of M channels in the regulation of action potential propagation and neurotransmitter release. KCNQ2 and KCNQ3 could be coimmunoprecipitated from brain lysates. Further, both proteins were coassociated with tubulin (see <a href="/entry/602529">602529</a>) and protein kinase A (see <a href="/entry/176911">176911</a>) within a triton X-100-insoluble protein complex. <a href="#6" class="mim-tip-reference" title="Cooper, E. C., Aldape, K. D., Abosch, A., Barbaro, N. M., Berger, M. S., Peacock, W. S., Jan, Y. N., Jan, L. Y. <strong>Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy.</strong> Proc. Nat. Acad. Sci. 97: 4914-4919, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10781098/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10781098</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10781098[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.090092797" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10781098">Cooper et al. (2000)</a> suggested that these studies provided a view of a signaling complex that may be important for cognitive function as well as epilepsy, and that analysis of this complex may shed light on the transduction pathway linking muscarinic acetylcholine receptor (see <a href="/entry/118510">118510</a>) activation to M-channel inhibition. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10781098" 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 recording channel currents produced in cRNA-injected Xenopus oocytes, <a href="#20" class="mim-tip-reference" title="Zhang, H., Craciun, L. C., Mirshahi, T., Rohacs, T., Lopes, C. M. B., Jin, T., Logothetis, D. E. <strong>PIP(2) activates KCNQ channels, and its hydrolysis underlies receptor-mediated inhibition of M currents.</strong> Neuron 37: 963-975, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12670425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12670425</a>] [<a href="https://doi.org/10.1016/s0896-6273(03)00125-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12670425">Zhang et al. (2003)</a> found that phosphatidylinositol (4,5)-bisphosphate (PIP2) activated all members of the KCNQ channel family analyzed, including human KCNQ2 and heterodimers of human KCNQ2 and rat Kcnq3. Similar results were obtained with mammalian cells expressing KCNQ2 and Kcnq3. Mutation of his328-to-cys in KCNQ2 and his330-to-cys in Kcnq3 reduced or eliminated PIP2-mediated channel activation. Wortmannin, a pharmacologic inhibitor of PIP2 regeneration, slowed the recovery from PIP2 hydrolysis and decreased the sensitivity of the KCNQ2/Kcnq3 channel to PIP2. <a href="#20" class="mim-tip-reference" title="Zhang, H., Craciun, L. C., Mirshahi, T., Rohacs, T., Lopes, C. M. B., Jin, T., Logothetis, D. E. <strong>PIP(2) activates KCNQ channels, and its hydrolysis underlies receptor-mediated inhibition of M currents.</strong> Neuron 37: 963-975, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12670425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12670425</a>] [<a href="https://doi.org/10.1016/s0896-6273(03)00125-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12670425">Zhang et al. (2003)</a> concluded that PIP2 acts as a membrane-diffusible second messenger to regulate the activity of KCNQ currents. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12670425" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Benign Familial Neonatal Seizures 1</em></strong></p><p>
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In affected members of a family with benign familial neonatal seizures-1 (BFNS1; <a href="/entry/121200">121200</a>), <a href="#14" class="mim-tip-reference" title="Singh, N. A., Charlier, C., Stauffer, D., DuPont, B. R., Leach, R. J., Melis, R., Ronen, G. M., Bjerre, I., Quattlebaum, T., Murphy, J. V., McHarg, M. L., Gagnon, D., Rosales, T. O., Peiffer, A., Anderson, V. E., Leppert, M. <strong>A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns.</strong> Nature Genet. 18: 25-29, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9425895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9425895</a>] [<a href="https://doi.org/10.1038/ng0198-25" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9425895">Singh et al. (1998)</a> identified a small deletion on chromosome 20q encompassing the KCNQ2 gene. The finding was confirmed by fluorescence in situ hybridization in an affected individual who presented with seizures beginning at 3 days and had 118 generalized seizures until the age of 23 days. A single seizure was observed at 3.5 months in conjunction with an acute infection of the middle ear with fever, but no seizures were observed thereafter. <a href="#14" class="mim-tip-reference" title="Singh, N. A., Charlier, C., Stauffer, D., DuPont, B. R., Leach, R. J., Melis, R., Ronen, G. M., Bjerre, I., Quattlebaum, T., Murphy, J. V., McHarg, M. L., Gagnon, D., Rosales, T. O., Peiffer, A., Anderson, V. E., Leppert, M. <strong>A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns.</strong> Nature Genet. 18: 25-29, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9425895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9425895</a>] [<a href="https://doi.org/10.1038/ng0198-25" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9425895">Singh et al. (1998)</a> also identified different heterozygous mutations in the KCNQ2 gene (see, e.g., <a href="#0001">602235.0001</a> and <a href="#0002">602235.0002</a>) in additional families with BFNS1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9425895" 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 large pedigree with BFNS1, <a href="#3" class="mim-tip-reference" title="Biervert, C., Schroeder, B. C., Kubisch, C., Berkovic, S. F., Propping, P., Jentsch, T. J., Steinlein, O. K. <strong>A potassium channel mutation in neonatal human epilepsy.</strong> Science 279: 403-406, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9430594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9430594</a>] [<a href="https://doi.org/10.1126/science.279.5349.403" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9430594">Biervert et al. (1998)</a> found a 5-bp insertion (<a href="#0003">602235.0003</a>) that was predicted to delete more than 300 amino acids from the C terminus of KCNQ2. Expression of the mutant channel did not yield measurable currents. Thus, impairment of potassium-dependent repolarization was indicated as the cause of this age-specific epileptic syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9430594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Dedek, K., Kunath, B., Kananura, C., Reuner, U., Jentsch, T. J., Steinlein, O. K. <strong>Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor of the KCNQ2 K(+) channel.</strong> Proc. Nat. Acad. Sci. 98: 12272-12277, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11572947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11572947</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11572947[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.211431298" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11572947">Dedek et al. (2001)</a> reported a Caucasian family in which BFNS was followed later in life by myokymia, involuntary contractions of skeletal muscles (see <a href="/entry/121200">121200</a>). All affected members of the family carried an arg207-to-trp mutation (R207W; <a href="#0006">602235.0006</a>) that neutralized a charged amino acid in the S4 voltage-sensor segment of KCNQ2. This substitution led to a shift of voltage-dependent activation of KCNQ2 and a dramatic slowing of activation upon depolarization. Myokymia was thought to result from hyperexcitability of the lower motoneuron; indeed both KCNQ2 and KCNQ3 mRNAs were detected in the anterior horn of the spinal cord where the cells of the lower motoneurons arise. <a href="#8" class="mim-tip-reference" title="Dedek, K., Kunath, B., Kananura, C., Reuner, U., Jentsch, T. J., Steinlein, O. K. <strong>Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor of the KCNQ2 K(+) channel.</strong> Proc. Nat. Acad. Sci. 98: 12272-12277, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11572947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11572947</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11572947[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.211431298" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11572947">Dedek et al. (2001)</a> proposed that a difference in firing patterns between motoneurons and central neurons, combined with the drastically slowed voltage activation of the R207W mutant, explained by this particular KCNQ2 mutant caused myokymia in addition to BFNC. <a href="#17" class="mim-tip-reference" title="Wuttke, T. V., Jurkat-Rott, K., Paulus, W., Garncarek, M., Lehmann-Horn, F., Lerche, H. <strong>Peripheral nerve hyperexcitability due to dominant-negative KCNQ2 mutations.</strong> Neurology 69: 2045-2053, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17872363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17872363</a>] [<a href="https://doi.org/10.1212/01.wnl.0000275523.95103.36" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17872363">Wuttke et al. (2007)</a> identified a mutation in the KCNQ2 gene (R207Q; <a href="#0011">602235.0011</a>) in a patient with isolated myokymia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11572947+17872363" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Heron, S. E., Cox, K., Grinton, B. E., Zuberi, S. M., Kivity, S., Afawi, Z., Straussberg, R., Berkovic, S. F., Scheffer, I. E., Mulley, J. C. <strong>Deletions or duplications in KCNQ2 can cause benign familial neonatal seizures. (Letter)</strong> J. Med. Genet. 44: 791-796, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17675531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17675531</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17675531[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/10.1136/jmg.2007.051938" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17675531">Heron et al. (2007)</a> identified 3 deletions and 1 duplication of more than 1 exon of the KCNQ2 gene in 4 (44%) of 9 unrelated families with benign familial neonatal seizures who had previously tested negative for coding or splice site mutations. The changes were predicted to result in haploinsufficiency. The authors suggested that multiplex ligation-dependent probe amplification (MLPA) should be a second-tier testing strategy in candidate cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17675531" 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>Developmental and Epileptic Encephalopathy 7</em></strong></p><p>
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In a boy with developmental and epileptic encephalopathy-7 (DEE7; <a href="/entry/613720">613720</a>), <a href="#7" class="mim-tip-reference" title="Dedek, K., Fusco, L., Teloy, N., Steinlein, O. K. <strong>Neonatal convulsions and epileptic encephalopathy in an Italian family with a missense mutation in the fifth transmembrane region of KCNQ2.</strong> Epilepsy Res. 54: 21-27, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12742592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12742592</a>] [<a href="https://doi.org/10.1016/s0920-1211(03)00037-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12742592">Dedek et al. (2003)</a> identified a heterozygous missense mutation in the KCNQ2 gene (S247W; <a href="#0008">602235.0008</a>). Functional expression studies showed that the S247W mutation reduced channel currents by more than 50% in homomeric KCNQ2 channels. The mutation was inherited from his mother, who had a milder phenotype with resolution of seizures in infancy and subsequent normal development. The son had onset of seizures at day 3 of life and the mother at age 1 month. <a href="#7" class="mim-tip-reference" title="Dedek, K., Fusco, L., Teloy, N., Steinlein, O. K. <strong>Neonatal convulsions and epileptic encephalopathy in an Italian family with a missense mutation in the fifth transmembrane region of KCNQ2.</strong> Epilepsy Res. 54: 21-27, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12742592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12742592</a>] [<a href="https://doi.org/10.1016/s0920-1211(03)00037-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12742592">Dedek et al. (2003)</a> emphasized that some KCNQ2 mutations may be associated with a more severe phenotype than is typical for BFNS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12742592" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Weckhuysen, S., Mandelstam, S., Suls, A., Audenaert, D., Deconinck, T., Claes, L. R. F., Deprez, L., Smets, K., Hristova, D., Yordanova, I., Jordanova, A., Ceulemans, B., and 11 others. <strong>KCNQ2 encephalopathy: emerging phenotype of a neonatal epileptic encephalopathy.</strong> Ann. Neurol. 71: 15-25, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22275249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22275249</a>] [<a href="https://doi.org/10.1002/ana.22644" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22275249">Weckhuysen et al. (2012)</a> identified 7 different heterozygous mutations in the KCNQ2 gene (see, e.g., <a href="#0012">602235.0012</a>-<a href="#0014">602235.0014</a>) in 8 (10%) of 80 patients with neonatal or early infantile seizures and associated psychomotor retardation. The mutations arose de novo in 7 cases; in 1 case, a severely affected patient inherited the mutation from her father, who had a milder phenotype and was mosaic for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22275249" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Saitsu, H., Kato, M., Koide, A., Goto, T., Fujita, T., Nishiyama, K., Tsurusaki, Y., Doi, H., Miyake, N., Hayasaka, K., Matsumoto, N. <strong>Whole exome sequencing identifies KCNQ2 mutations in Ohtahara syndrome.</strong> Ann. Neurol. 72: 298-300, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22926866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22926866</a>] [<a href="https://doi.org/10.1002/ana.23620" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22926866">Saitsu et al. (2012)</a> identified 3 different de novo missense mutations in the KCNQ2 gene (see, e.g., A265V, <a href="#0015">602235.0015</a>) in 3 of 12 Japanese patients with DEE and onset of seizures in the first week of life. The mutations were found by whole-exome sequencing. The findings suggested that KCNQ2 mutations may be a common cause of this disorder. Functional studies of the variants were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22926866" 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 high-resolution melting analysis or whole-exome sequencing of 239 patients with DEE, <a href="#10" class="mim-tip-reference" title="Kato, M., Yamagata, T., Kubota, M., Arai, H., Yamashita, S., Nakagawa, T., Fujii, T., Sugai, K., Imai, K., Uster, T., Chitayat, D., Weiss, S., and 15 others. <strong>Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation.</strong> Epilepsia 54: 1282-1287, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23621294/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23621294</a>] [<a href="https://doi.org/10.1111/epi.12200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23621294">Kato et al. (2013)</a> found that 12 patients carried a total of 10 heterozygous missense mutations in the KCNQ2 gene. The mutations occurred de novo in all patients except 1, who inherited the mutation from her mildly affected mother who was somatic mosaic for the mutation. Several of the mutations had previously been reported (see, e.g., A265V, <a href="#0015">602235.0015</a>), but functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23621294" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The electroconvulsive threshold (ECT) test has been used extensively to determine the protection conferred by antiepileptic drug candidates against induced seizures in rodents. <a href="#19" class="mim-tip-reference" title="Yang, Y., Beyer, B. J., Otto, J. F., O'Brien, T. P., Letts, V. A., White, H. S., Frankel, W. N. <strong>Spontaneous deletion of epilepsy gene orthologs in a mutant mouse with a low electroconvulsive threshold.</strong> Hum. Molec. Genet. 12: 975-984, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12700166/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12700166</a>] [<a href="https://doi.org/10.1093/hmg/ddg118" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12700166">Yang et al. (2003)</a> adopted the ECT test to screen the progeny of ethylnitrosourea-treated male C57BL/6J mice. In a small-scale screen, several mutant lines conferring a low threshold to ECT minimal clonic seizures were mapped to the telomeric region of mouse chromosome 2 in independent founder families. Genetic and physical mapping data indicated that several lines shared a single mutation, Szt1 (seizure threshold-1), consisting of a 300-kb deletion of genomic DNA involving 3 known genes. Two of these genes, Kcnq2 and Chrna4 (<a href="/entry/118504">118504</a>), are known to be mutated in human epilepsy families. Szt1 homozygotes and heterozygotes displayed similar phenotypes to those found in the respective Kcnq2 knockout mutant mice, suggesting that Kcnq2 haploinsufficiency may lie at the root of the Szt1 seizure sensitivity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12700166" 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="/allelicVariants/602235" class="btn btn-default" role="button"> Table View </a>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=602235[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28939683 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28939683;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=rs28939683" 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=rs28939683" 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=RCV000007806 OR RCV003315290" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007806, RCV003315290" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007806...</a>
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<p>In affected members of a family with benign familial neonatal seizures (BFNS1; <a href="/entry/121200">121200</a>), <a href="#14" class="mim-tip-reference" title="Singh, N. A., Charlier, C., Stauffer, D., DuPont, B. R., Leach, R. J., Melis, R., Ronen, G. M., Bjerre, I., Quattlebaum, T., Murphy, J. V., McHarg, M. L., Gagnon, D., Rosales, T. O., Peiffer, A., Anderson, V. E., Leppert, M. <strong>A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns.</strong> Nature Genet. 18: 25-29, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9425895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9425895</a>] [<a href="https://doi.org/10.1038/ng0198-25" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9425895">Singh et al. (1998)</a> demonstrated a TAC-to-TGC transition converting codon 284 from tyrosine to cysteine. The family was too small to permit demonstration of linkage to chromosome 20. The mutation occurred in the pore region of the channel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9425895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002 SEIZURES, BENIGN FAMILIAL NEONATAL, 1</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">rs74315390 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74315390;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=rs74315390" 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=rs74315390" 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=RCV000007807 OR RCV001245227 OR RCV001564572 OR RCV002264637 OR RCV002316186 OR RCV003315291" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007807, RCV001245227, RCV001564572, RCV002264637, RCV002316186, RCV003315291" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007807...</a>
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<p>In kindred 1705, <a href="#14" class="mim-tip-reference" title="Singh, N. A., Charlier, C., Stauffer, D., DuPont, B. R., Leach, R. J., Melis, R., Ronen, G. M., Bjerre, I., Quattlebaum, T., Murphy, J. V., McHarg, M. L., Gagnon, D., Rosales, T. O., Peiffer, A., Anderson, V. E., Leppert, M. <strong>A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns.</strong> Nature Genet. 18: 25-29, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9425895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9425895</a>] [<a href="https://doi.org/10.1038/ng0198-25" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9425895">Singh et al. (1998)</a> demonstrated that individuals affected with benign familial neonatal seizures (BFNS1; <a href="/entry/121200">121200</a>) had an ala306-to-thr (A306T) amino acid substitution in the S6 transmembrane segment. This alanine residue was conserved in all members of the Shaker, Shab, Shaw, and Shal subfamilies of potassium channels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9425895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 SEIZURES, BENIGN FAMILIAL NEONATAL, 1</strong>
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KCNQ2, 5-BP INS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs118192231 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192231;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=rs118192231" 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=rs118192231" 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=RCV000415727" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000415727" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000415727</a>
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<p><a href="#3" class="mim-tip-reference" title="Biervert, C., Schroeder, B. C., Kubisch, C., Berkovic, S. F., Propping, P., Jentsch, T. J., Steinlein, O. K. <strong>A potassium channel mutation in neonatal human epilepsy.</strong> Science 279: 403-406, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9430594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9430594</a>] [<a href="https://doi.org/10.1126/science.279.5349.403" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9430594">Biervert et al. (1998)</a> identified an insertional mutation in the KCNQ2 gene in a large Australian Caucasian pedigree with benign familial neonatal seizures (BFNS1; <a href="/entry/121200">121200</a>) previously reported by <a href="#2" class="mim-tip-reference" title="Berkovic, S. F., Kennerson, M. L., Howell, R. A., Scheffer, I. E., Hwang, P. A., Nicholson, G. A. <strong>Phenotypic expression of benign familial neonatal convulsions linked to chromosome 20.</strong> Arch. Neurol. 51: 1125-1128, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7980108/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7980108</a>] [<a href="https://doi.org/10.1001/archneur.1994.00540230063014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7980108">Berkovic et al. (1994)</a>. <a href="#3" class="mim-tip-reference" title="Biervert, C., Schroeder, B. C., Kubisch, C., Berkovic, S. F., Propping, P., Jentsch, T. J., Steinlein, O. K. <strong>A potassium channel mutation in neonatal human epilepsy.</strong> Science 279: 403-406, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9430594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9430594</a>] [<a href="https://doi.org/10.1126/science.279.5349.403" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9430594">Biervert et al. (1998)</a> found a heterozygous 5-bp insertion at the triplet encoding amino acid 534 in a segment highly conserved between KCNQ2 and KCNQ1 (<a href="/entry/607542">607542</a>), which is mutated in type 1 long QT syndrome (<a href="/entry/192500">192500</a>). The resulting frameshift was predicted to cause a premature stop, which would truncate more than 300 amino acids. Of 13 affected family members, 10 had known neonatal seizures. Two patients had afebrile seizures later, 1 of whom did not have neonatal seizures. One mutation carrier was unaffected, indicating reduced penetrance. <a href="#2" class="mim-tip-reference" title="Berkovic, S. F., Kennerson, M. L., Howell, R. A., Scheffer, I. E., Hwang, P. A., Nicholson, G. A. <strong>Phenotypic expression of benign familial neonatal convulsions linked to chromosome 20.</strong> Arch. Neurol. 51: 1125-1128, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7980108/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7980108</a>] [<a href="https://doi.org/10.1001/archneur.1994.00540230063014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7980108">Berkovic et al. (1994)</a> noted the phenotypic heterogeneity in this family. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9430594+7980108" 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 SEIZURES, BENIGN FAMILIAL NEONATAL, 1</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">rs118192241 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192241;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=rs118192241" 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=rs118192241" 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=RCV000678065" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000678065" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000678065</a>
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<p>In a patient with benign familial neonatal seizures (BFNS1; <a href="/entry/121200">121200</a>), <a href="#4" class="mim-tip-reference" title="Biervert, C., Steinlein, O. K. <strong>Structural and mutational analysis of KCNQ2, the major gene locus for benign familial neonatal convulsions.</strong> Hum. Genet. 104: 234-240, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10323247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10323247</a>] [<a href="https://doi.org/10.1007/pl00008713" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10323247">Biervert and Steinlein (1999)</a> identified a 1-bp deletion, 1846delT, in the KCNQ2 gene that caused a frameshift in exon 16, removing 228 amino acids from the predicted wildtype sequence and replacing them with a stretch of 283 amino acids showing a completely different sequence. The mutation was also present in the DNA sample obtained from the father but not in that from the mother. The paternal grandmother reportedly had also suffered from neonatal seizures but was not available for study. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10323247" 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 SEIZURES, BENIGN FAMILIAL NEONATAL, 1</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">rs28939684 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28939684;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=rs28939684" 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=rs28939684" 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=RCV000007810 OR RCV000790713 OR RCV001851725 OR RCV003315292 OR RCV004786244" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007810, RCV000790713, RCV001851725, RCV003315292, RCV004786244" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007810...</a>
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<p>In a 4-generation Italian family segregating benign familial neonatal seizures (BFNS1; <a href="/entry/121200">121200</a>), <a href="#11" class="mim-tip-reference" title="Miraglia Del Giudice, E., Coppola, G., Scuccimarra, G., Cirillo, G., Bellini, G., Pascotto, A. <strong>Benign familial neonatal convulsions (BFNC) resulting from mutation of the KCNQ2 voltage sensor.</strong> Europ. J. Hum. Genet. 8: 994-997, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11175290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11175290</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200570" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11175290">Miraglia Del Giudice et al. (2000)</a> identified a 686C-T mutation in exon 3 of the KCNQ2 gene, resulting in an arg214-to-trp substitution. The mutation was found in the 8 affected members of the pedigree and in 1 unaffected subject who was an obligate carrier. The mutation occurred in the transmembrane domain S4, neutralizing one of the conserved, positively charged residues of that segment. The substitution abolished an AgeI restriction site and was not detected in 150 Italian controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11175290" 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">rs74315391 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74315391;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=rs74315391" 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=rs74315391" 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=RCV000007811 OR RCV000187862 OR RCV000623725 OR RCV000636312 OR RCV000678084 OR RCV002255996 OR RCV003315293" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007811, RCV000187862, RCV000623725, RCV000636312, RCV000678084, RCV002255996, RCV003315293" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007811...</a>
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<p>In 5 affected members of a Caucasian family with benign familial neonatal seizures and/or myokymia (see <a href="/entry/121200">121200</a>), <a href="#8" class="mim-tip-reference" title="Dedek, K., Kunath, B., Kananura, C., Reuner, U., Jentsch, T. J., Steinlein, O. K. <strong>Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor of the KCNQ2 K(+) channel.</strong> Proc. Nat. Acad. Sci. 98: 12272-12277, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11572947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11572947</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11572947[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.211431298" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11572947">Dedek et al. (2001)</a> identified a heterozygous C-to-T transition in exon 3 of the KCNQ2 gene, resulting in an arg207-to-trp (R207W) substitution in the fourth transmembrane domain. Three mutation carriers had BFNS with myokymia, 1 had isolated myokymia without seizures, and 1 had neonatal seizures with no clinical signs of myokymia, although electromyography demonstrated spontaneous discharges of grouped motor unit potentials. In vitro functional expression studies showed that the mutation resulted in a shift of voltage-dependent activation of KCNQ2 and a dramatic slowing of activation upon depolarization. The loss of potassium current was more severe compared to other KCNQ2 mutations and showed a dominant-negative effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11572947" 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 patient with isolated myokymia and no history of neonatal seizures, <a href="#17" class="mim-tip-reference" title="Wuttke, T. V., Jurkat-Rott, K., Paulus, W., Garncarek, M., Lehmann-Horn, F., Lerche, H. <strong>Peripheral nerve hyperexcitability due to dominant-negative KCNQ2 mutations.</strong> Neurology 69: 2045-2053, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17872363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17872363</a>] [<a href="https://doi.org/10.1212/01.wnl.0000275523.95103.36" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17872363">Wuttke et al. (2007)</a> identified an R207Q mutation (<a href="#0011">602235.0011</a>) in the same codon as the R207W mutation. In vitro functional expression studies showed that mutant R207W and R207Q channels had large depolarizing shifts and marked slowing of activation time compared to wildtype channels. Coexpression with wildtype channels showed a dominant-negative effect reducing the current amplitude by 70% after short depolarization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17872363" 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">rs267607198 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607198;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=rs267607198" 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=rs267607198" 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=RCV000007813 OR RCV000678105 OR RCV001260874 OR RCV002292456" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007813, RCV000678105, RCV001260874, RCV002292456" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007813...</a>
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<p>In 4 affected members of a family with benign familial neonatal seizures (BFNS1; <a href="/entry/121200">121200</a>), <a href="#5" class="mim-tip-reference" title="Borgatti, R., Zucca, C., Cavallini, A., Ferrario, M., Panzeri, C., Castaldo, P., Soldovieri, M. V., Baschirotto, C., Bresolin, N., Dalla Bernardina, B., Taglialatela, M., Bassi, M. T. <strong>A novel mutation in KCNQ2 associated with BFNC, drug resistant epilepsy, and mental retardation.</strong> Neurology 63: 57-65, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15249611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15249611</a>] [<a href="https://doi.org/10.1212/01.wnl.0000132979.08394.6d" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15249611">Borgatti et al. (2004)</a> identified a heterozygous 1620G-A transition in the KCNQ2 gene, resulting in a lys526-to-asn (K526N) substitution in the C-terminal region of the protein. The mutation is located in a highly conserved region within alpha-helix B that is necessary for calmodulin binding. Functional expression studies showed that the K526N mutation decreased the voltage-dependence of the channel. Although 2 patients had a phenotype consistent with typical BFNS, the other 2 patients had a complex phenotype that was atypical and severe, consistent with developmental and epileptic encephalopathy (DEE7; <a href="/entry/613720">613720</a>). One developed an extremely unfavorable outcome, profound mental retardation, and spastic quadriparesis. The other continued to have focal seizures until late infancy with a moderate degree of mental retardation and a mild cerebellar syndrome. <a href="#5" class="mim-tip-reference" title="Borgatti, R., Zucca, C., Cavallini, A., Ferrario, M., Panzeri, C., Castaldo, P., Soldovieri, M. V., Baschirotto, C., Bresolin, N., Dalla Bernardina, B., Taglialatela, M., Bassi, M. T. <strong>A novel mutation in KCNQ2 associated with BFNC, drug resistant epilepsy, and mental retardation.</strong> Neurology 63: 57-65, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15249611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15249611</a>] [<a href="https://doi.org/10.1212/01.wnl.0000132979.08394.6d" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15249611">Borgatti et al. (2004)</a> noted that some patients with BFNS may experience seizures later in life or a different set of epileptic subtypes sometimes associated with severe neurologic and intellectual impairment. Overall, the clinical, genetic, and functional data did not provide a definitive explanation for the wide range of phenotypic variability observed in the described family, therefore preventing genotype-phenotype correlations. The authors postulated that the phenotypic variability could be due to the interplay of pathogenic mutations, modifier genes, and more subtle environmental factors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15249611" 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">rs74315392 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74315392;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=rs74315392" 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=rs74315392" 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=RCV000030664 OR RCV000678092 OR RCV001059860 OR RCV003441710" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000030664, RCV000678092, RCV001059860, RCV003441710" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000030664...</a>
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<p>In a boy with developmental and epileptic encephalopathy-7 (DEE7; <a href="/entry/613720">613720</a>), <a href="#7" class="mim-tip-reference" title="Dedek, K., Fusco, L., Teloy, N., Steinlein, O. K. <strong>Neonatal convulsions and epileptic encephalopathy in an Italian family with a missense mutation in the fifth transmembrane region of KCNQ2.</strong> Epilepsy Res. 54: 21-27, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12742592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12742592</a>] [<a href="https://doi.org/10.1016/s0920-1211(03)00037-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12742592">Dedek et al. (2003)</a> identified a heterozygous C-to-G transversion in exon 5 of the KCNQ2 gene, resulting in a ser247-to-trp (S247W) substitution in the fifth transmembrane residue of the protein. The mutation was not identified in 202 control chromosomes. Functional expression studies showed that the S247W mutation reduced channel currents by more than 50% in homomeric KCNQ2 channels. The mutation was inherited from his mother, who had a milder phenotype with resolution of seizures in infancy and subsequent normal development. The son had onset of seizures at day 3 of life and the mother at age 1 month. <a href="#7" class="mim-tip-reference" title="Dedek, K., Fusco, L., Teloy, N., Steinlein, O. K. <strong>Neonatal convulsions and epileptic encephalopathy in an Italian family with a missense mutation in the fifth transmembrane region of KCNQ2.</strong> Epilepsy Res. 54: 21-27, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12742592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12742592</a>] [<a href="https://doi.org/10.1016/s0920-1211(03)00037-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12742592">Dedek et al. (2003)</a> emphasized that some KCNQ2 mutations may be associated with a more severe phenotype than is typical for BFNS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12742592" 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">rs118192197 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192197;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=rs118192197" 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=rs118192197" 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=RCV000678081 OR RCV002269819" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000678081, RCV002269819" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000678081...</a>
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<p>In 9 affected members of a large Italian family with benign familial neonatal seizures (BFNS1; <a href="/entry/121200">121200</a>), <a href="#1" class="mim-tip-reference" title="Bassi, M. T., Balottin, U., Panzeri, C., Piccinelli, P., Castaldo, P., Barrese, V., Soldovieri, M. V., Miceli, F., Colombo, M., Bresolin, N., Borgatti, R., Taglialatela, M. <strong>Functional analysis of novel KCNQ2 and KCNQ3 gene variants found in a large pedigree with benign familial neonatal convulsions (BFNC).</strong> Neurogenetics 6: 185-193, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16235065/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16235065</a>] [<a href="https://doi.org/10.1007/s10048-005-0012-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16235065">Bassi et al. (2005)</a> identified a heterozygous 10-bp deletion and 1-bp insertion (761del10insA) in cis in the KCNQ2 gene, resulting in a truncated N-terminal peptide of 194 residues. The resultant mutant protein lacks the S4 domain, which is critical for voltage sensing. In vitro functional expression studies showed that the mutant KCNQ2 subunit was unable to form functional homomeric potassium channels, suggesting haploinsufficiency rather than a dominant-negative effect. One affected family member developed severe epilepsy associated with mild mental retardation and persistent neurologic problems in adult life; this phenotypic variability was considered by the authors to be consistent with the fact that 10 to 15% of BFNS individuals experience seizure manifestations later in life. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16235065" 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> rs118192244 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192244;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/rs118192244?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=rs118192244" 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=rs118192244" 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=RCV000007814 OR RCV000187948 OR RCV000578304 OR RCV001389321" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007814, RCV000187948, RCV000578304, RCV001389321" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007814...</a>
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<p>In affected members of a family with benign familial neonatal seizures (BFNS1; <a href="/entry/121200">121200</a>), originally reported by <a href="#12" class="mim-tip-reference" title="Rett, A., Teubel, R. <strong>Neugeborenenkraempfe im Rahmen einer epileptisch belasteten Familie.</strong> Wien. Klin. Wschr. 76: 609-613, 1964."None>Rett and Teubel (1964)</a>, <a href="#21" class="mim-tip-reference" title="Zimprich, F., Ronen, G. M., Stogmann, W., Baumgartner, C., Stogmann, E., Rett, B., Pappas, C., Leppert, M., Singh, N., Anderson, V. E. <strong>Andreas Rett and benign familial neonatal convulsions revisited.</strong> Neurology 67: 864-866, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16966552/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16966552</a>] [<a href="https://doi.org/10.1212/01.wnl.0000234066.46806.90" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16966552">Zimprich et al. (2006)</a> identified a heterozygous 1-bp deletion (2127delT) in the last exon of the KCNQ2 gene, resulting in a replacement of the C terminus with 219 new amino acids and a protein that is 56 residues longer than the wildtype protein. Three of the 9 affected individuals later developed childhood nocturnal generalized tonic-clonic seizures; 2 of the 3 also had simple focal orofacial seizures. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16966552" 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 SEIZURES, BENIGN FAMILIAL NEONATAL, 1, AND/OR MYOKYMIA</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">rs118192200 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192200;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=rs118192200" 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=rs118192200" 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=RCV000007815 OR RCV000187863 OR RCV000678085 OR RCV000763453 OR RCV001205287 OR RCV003315294 OR RCV004732533" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007815, RCV000187863, RCV000678085, RCV000763453, RCV001205287, RCV003315294, RCV004732533" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007815...</a>
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<p>In a 25-year-old Egyptian man with isolated myokymia (see <a href="/entry/121200">121200</a>), <a href="#17" class="mim-tip-reference" title="Wuttke, T. V., Jurkat-Rott, K., Paulus, W., Garncarek, M., Lehmann-Horn, F., Lerche, H. <strong>Peripheral nerve hyperexcitability due to dominant-negative KCNQ2 mutations.</strong> Neurology 69: 2045-2053, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17872363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17872363</a>] [<a href="https://doi.org/10.1212/01.wnl.0000275523.95103.36" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17872363">Wuttke et al. (2007)</a> identified a heterozygous G-to-A transition in the KCNQ2 gene, resulting in an arg207-to-gln (R207Q) substitution in a highly conserved residue in the voltage sensor region of the potassium channel. He had no history of neonatal seizures and no family history of epilepsy or peripheral nerve hyperexcitability. Clinically, he had permanent muscle overactivity in the distal upper extremities and small amplitude movements of the fingers, which were not disabling. However, he also reported exercise-induced cramps of both hands since childhood and 4 episodes of exercise-induced generalized muscle stiffness. EMG showed spontaneous irregular discharges consistent with myokymia. <a href="#17" class="mim-tip-reference" title="Wuttke, T. V., Jurkat-Rott, K., Paulus, W., Garncarek, M., Lehmann-Horn, F., Lerche, H. <strong>Peripheral nerve hyperexcitability due to dominant-negative KCNQ2 mutations.</strong> Neurology 69: 2045-2053, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17872363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17872363</a>] [<a href="https://doi.org/10.1212/01.wnl.0000275523.95103.36" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17872363">Wuttke et al. (2007)</a> noted that a mutation in the same codon (R207W; <a href="#0006">602235.0006</a>) had been associated with neonatal epilepsy and/or myokymia. In vitro functional expression studies showed that mutant R207W and R207Q channels had large depolarizing shifts and marked slowing of activation time compared to wildtype channels. Coexpression with wildtype channels showed a dominant-negative effect reducing the current amplitude by 70% after short depolarization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17872363" 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>.0012 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 7</strong>
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KCNQ2, ARG213GLN
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000032979 OR RCV000187867 OR RCV000698323 OR RCV000763452 OR RCV002354177" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032979, RCV000187867, RCV000698323, RCV000763452, RCV002354177" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032979...</a>
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<p>In a girl with developmental and epileptic encephalopathy (DEE7; <a href="/entry/613720">613720</a>), <a href="#16" class="mim-tip-reference" title="Weckhuysen, S., Mandelstam, S., Suls, A., Audenaert, D., Deconinck, T., Claes, L. R. F., Deprez, L., Smets, K., Hristova, D., Yordanova, I., Jordanova, A., Ceulemans, B., and 11 others. <strong>KCNQ2 encephalopathy: emerging phenotype of a neonatal epileptic encephalopathy.</strong> Ann. Neurol. 71: 15-25, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22275249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22275249</a>] [<a href="https://doi.org/10.1002/ana.22644" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22275249">Weckhuysen et al. (2012)</a> identified a heterozygous 638G-A transition in the KCNQ2 gene, resulting in an arg213-to-gln (R213Q) substitution at a highly conserved residue in the transmembrane domain. The mutation was not found in 276 control individuals. The patient had onset of multiple daily seizures on the second day of life, and the mother had noted jerking movements during pregnancy. The patient had poor response to treatment, but the seizures remitted at age 14 months. However, at age 2 years 10 months, she had severe psychomotor retardation, could not roll over, was nonverbal, had severe spastic quadriplegia, and some dysmorphic features. Her father, who had benign neonatal seizures and myokymia, was mosaic for the mutation, which was found in 30% of his lymphocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22275249" 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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<strong>.0013 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 7</strong>
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KCNQ2, MET546VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397515420 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397515420;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=rs397515420" 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=rs397515420" 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=RCV000032980 OR RCV002225272" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032980, RCV002225272" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032980...</a>
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<p>In a 9-year-old boy with developmental and epileptic encephalopathy (DEE7; <a href="/entry/613720">613720</a>), <a href="#16" class="mim-tip-reference" title="Weckhuysen, S., Mandelstam, S., Suls, A., Audenaert, D., Deconinck, T., Claes, L. R. F., Deprez, L., Smets, K., Hristova, D., Yordanova, I., Jordanova, A., Ceulemans, B., and 11 others. <strong>KCNQ2 encephalopathy: emerging phenotype of a neonatal epileptic encephalopathy.</strong> Ann. Neurol. 71: 15-25, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22275249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22275249</a>] [<a href="https://doi.org/10.1002/ana.22644" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22275249">Weckhuysen et al. (2012)</a> identified a de novo heterozygous 1636A-G transition in the KCNQ2 gene, resulting in a met546-to-val (M546V) substitution at a highly conserved residue in one of the calmodulin binding domains in the C-terminal region. The mutation was not found in 276 control individuals. On the third day of life, the patient had onset of multiple daily tonic seizures resistant to treatment and associated with a burst suppression pattern on EEG that evolved into multifocal epileptic activity. Seizures remitted at age 3 years and the EEG was normal at age 8. However, he had psychomotor retardation, mild spasticity, widely spaced gait, and lack of speech development. Brain imaging showed lesions in the basal ganglia and a thin posterior corpus callosum. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22275249" 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>.0014 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 7</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">rs397514582 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514582;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=rs397514582" 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=rs397514582" 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=RCV000032981 OR RCV000498787 OR RCV000678147" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032981, RCV000498787, RCV000678147" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032981...</a>
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<p>In 2 unrelated patients with developmental and epileptic encephalopathy (DEE7; <a href="/entry/613720">613720</a>), <a href="#16" class="mim-tip-reference" title="Weckhuysen, S., Mandelstam, S., Suls, A., Audenaert, D., Deconinck, T., Claes, L. R. F., Deprez, L., Smets, K., Hristova, D., Yordanova, I., Jordanova, A., Ceulemans, B., and 11 others. <strong>KCNQ2 encephalopathy: emerging phenotype of a neonatal epileptic encephalopathy.</strong> Ann. Neurol. 71: 15-25, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22275249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22275249</a>] [<a href="https://doi.org/10.1002/ana.22644" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22275249">Weckhuysen et al. (2012)</a> identified a de novo heterozygous 869G-A transition in the KCNQ2 gene, resulting in a gly290-to-asp (G290D) substitution at a highly conserved residue in the transmembrane domain. The mutation was not found in 276 control individuals. Both patients had onset of multiple daily tonic seizures on the second day of life, but the seizures remitted at around age 3 years. EEG studies were abnormal at first, but normalized over time. Both patients showed psychomotor retardation and were nonverbal. One had axial hypotonia and widely spaced gait, whereas the other had spastic quadriparesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22275249" 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="0015" class="mim-anchor"></a>
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<strong>.0015 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 7</strong>
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KCNQ2, ALA265VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587777219 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777219;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=rs587777219" 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=rs587777219" 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=RCV000106299 OR RCV000187868 OR RCV000578260 OR RCV000768250 OR RCV001056302 OR RCV001089803 OR RCV002316289 OR RCV004546432" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000106299, RCV000187868, RCV000578260, RCV000768250, RCV001056302, RCV001089803, RCV002316289, RCV004546432" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000106299...</a>
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<p>In a 3-month-old Japanese boy with developmental and epileptic encephalopathy (DEE7; <a href="/entry/613720">613720</a>), <a href="#13" class="mim-tip-reference" title="Saitsu, H., Kato, M., Koide, A., Goto, T., Fujita, T., Nishiyama, K., Tsurusaki, Y., Doi, H., Miyake, N., Hayasaka, K., Matsumoto, N. <strong>Whole exome sequencing identifies KCNQ2 mutations in Ohtahara syndrome.</strong> Ann. Neurol. 72: 298-300, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22926866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22926866</a>] [<a href="https://doi.org/10.1002/ana.23620" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22926866">Saitsu et al. (2012)</a> identified a de novo heterozygous c.794C-T transition in the KCNQ2 gene, resulting in an ala265-to-val (A265V) substitution. The patient developed tonic spasms on the first day of life and then had intractable seizures associated with a suppression-burst pattern on EEG; he was diagnosed clinically with Ohtahara syndrome. He had delayed development and no eye pursuit. The patient was 1 of 12 probands with a similar disorder who underwent whole-exome sequencing. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22926866" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Kato, M., Yamagata, T., Kubota, M., Arai, H., Yamashita, S., Nakagawa, T., Fujii, T., Sugai, K., Imai, K., Uster, T., Chitayat, D., Weiss, S., and 15 others. <strong>Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation.</strong> Epilepsia 54: 1282-1287, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23621294/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23621294</a>] [<a href="https://doi.org/10.1111/epi.12200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23621294">Kato et al. (2013)</a> identified a de novo heterozygous A265V substitution in 2 unrelated Japanese patients with DEE7. The mutations, which were found by whole-exome sequencing, were not present in 212 control exomes. Onset of seizures in both patients occurred in the early neonatal period. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23621294" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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[<a href="https://doi.org/10.1007/s10048-005-0012-2" target="_blank">Full Text</a>]
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<a id="Berkovic1994" class="mim-anchor"></a>
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[<a href="https://doi.org/10.1001/archneur.1994.00540230063014" target="_blank">Full Text</a>]
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<a id="Biervert1998" class="mim-anchor"></a>
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[<a href="https://doi.org/10.1126/science.279.5349.403" target="_blank">Full Text</a>]
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<a id="Biervert1999" class="mim-anchor"></a>
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Biervert, C., Steinlein, O. K.
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<strong>Structural and mutational analysis of KCNQ2, the major gene locus for benign familial neonatal convulsions.</strong>
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Hum. Genet. 104: 234-240, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10323247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10323247</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10323247" 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/10.1007/pl00008713" target="_blank">Full Text</a>]
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Borgatti, R., Zucca, C., Cavallini, A., Ferrario, M., Panzeri, C., Castaldo, P., Soldovieri, M. V., Baschirotto, C., Bresolin, N., Dalla Bernardina, B., Taglialatela, M., Bassi, M. T.
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<strong>A novel mutation in KCNQ2 associated with BFNC, drug resistant epilepsy, and mental retardation.</strong>
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Neurology 63: 57-65, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15249611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15249611</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15249611" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/01.wnl.0000132979.08394.6d" target="_blank">Full Text</a>]
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<a id="Cooper2000" class="mim-anchor"></a>
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Cooper, E. C., Aldape, K. D., Abosch, A., Barbaro, N. M., Berger, M. S., Peacock, W. S., Jan, Y. N., Jan, L. Y.
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[<a href="https://doi.org/10.1073/pnas.090092797" target="_blank">Full Text</a>]
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<a id="Dedek2003" class="mim-anchor"></a>
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<strong>Neonatal convulsions and epileptic encephalopathy in an Italian family with a missense mutation in the fifth transmembrane region of KCNQ2.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12742592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12742592</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12742592" 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/s0920-1211(03)00037-8" target="_blank">Full Text</a>]
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<a id="Dedek2001" class="mim-anchor"></a>
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Dedek, K., Kunath, B., Kananura, C., Reuner, U., Jentsch, T. J., Steinlein, O. K.
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<strong>Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor of the KCNQ2 K(+) channel.</strong>
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Proc. Nat. Acad. Sci. 98: 12272-12277, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11572947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11572947</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11572947[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=11572947" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.211431298" target="_blank">Full Text</a>]
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<a id="Heron2007" class="mim-anchor"></a>
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Heron, S. E., Cox, K., Grinton, B. E., Zuberi, S. M., Kivity, S., Afawi, Z., Straussberg, R., Berkovic, S. F., Scheffer, I. E., Mulley, J. C.
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<strong>Deletions or duplications in KCNQ2 can cause benign familial neonatal seizures. (Letter)</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17675531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17675531</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17675531[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=17675531" 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/10.1136/jmg.2007.051938" target="_blank">Full Text</a>]
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Kato, M., Yamagata, T., Kubota, M., Arai, H., Yamashita, S., Nakagawa, T., Fujii, T., Sugai, K., Imai, K., Uster, T., Chitayat, D., Weiss, S., and 15 others.
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<strong>Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation.</strong>
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Epilepsia 54: 1282-1287, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23621294/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23621294</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23621294" 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/10.1111/epi.12200" target="_blank">Full Text</a>]
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Miraglia Del Giudice, E., Coppola, G., Scuccimarra, G., Cirillo, G., Bellini, G., Pascotto, A.
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<strong>Benign familial neonatal convulsions (BFNC) resulting from mutation of the KCNQ2 voltage sensor.</strong>
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Europ. J. Hum. Genet. 8: 994-997, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11175290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11175290</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11175290" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/sj.ejhg.5200570" target="_blank">Full Text</a>]
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Rett, A., Teubel, R.
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<strong>Neugeborenenkraempfe im Rahmen einer epileptisch belasteten Familie.</strong>
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Wien. Klin. Wschr. 76: 609-613, 1964.
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Saitsu2012" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Saitsu, H., Kato, M., Koide, A., Goto, T., Fujita, T., Nishiyama, K., Tsurusaki, Y., Doi, H., Miyake, N., Hayasaka, K., Matsumoto, N.
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<strong>Whole exome sequencing identifies KCNQ2 mutations in Ohtahara syndrome.</strong>
|
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Ann. Neurol. 72: 298-300, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22926866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22926866</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22926866" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.23620" 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="14" class="mim-anchor"></a>
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<a id="Singh1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Singh, N. A., Charlier, C., Stauffer, D., DuPont, B. R., Leach, R. J., Melis, R., Ronen, G. M., Bjerre, I., Quattlebaum, T., Murphy, J. V., McHarg, M. L., Gagnon, D., Rosales, T. O., Peiffer, A., Anderson, V. E., Leppert, M.
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<strong>A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns.</strong>
|
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Nature Genet. 18: 25-29, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9425895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9425895</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9425895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng0198-25" 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="15" class="mim-anchor"></a>
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<a id="Wang1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wang, H.-S., Pan, Z., Shi, W., Brown, B. S., Wymore, R. S., Cohen, I. S., Dixon, J. E., McKinnon, D.
|
|
<strong>KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel.</strong>
|
|
Science 282: 1890-1893, 1998.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9836639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9836639</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9836639" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.282.5395.1890" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="16" class="mim-anchor"></a>
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<a id="Weckhuysen2012" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Weckhuysen, S., Mandelstam, S., Suls, A., Audenaert, D., Deconinck, T., Claes, L. R. F., Deprez, L., Smets, K., Hristova, D., Yordanova, I., Jordanova, A., Ceulemans, B., and 11 others.
|
|
<strong>KCNQ2 encephalopathy: emerging phenotype of a neonatal epileptic encephalopathy.</strong>
|
|
Ann. Neurol. 71: 15-25, 2012.
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|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22275249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22275249</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22275249" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.22644" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="17" class="mim-anchor"></a>
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<a id="Wuttke2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wuttke, T. V., Jurkat-Rott, K., Paulus, W., Garncarek, M., Lehmann-Horn, F., Lerche, H.
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<strong>Peripheral nerve hyperexcitability due to dominant-negative KCNQ2 mutations.</strong>
|
|
Neurology 69: 2045-2053, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17872363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17872363</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17872363" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/01.wnl.0000275523.95103.36" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="18" class="mim-anchor"></a>
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<a id="Yang1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yang, W.-P., Levesque, P. C., Little, W. A., Conder, M. L., Ramakrishnan, P., Neubauer, M. G., Blanar, M. A.
|
|
<strong>Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy.</strong>
|
|
J. Biol. Chem. 273: 19419-19423, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9677360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9677360</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9677360" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.273.31.19419" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="19" class="mim-anchor"></a>
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<a id="Yang2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yang, Y., Beyer, B. J., Otto, J. F., O'Brien, T. P., Letts, V. A., White, H. S., Frankel, W. N.
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<strong>Spontaneous deletion of epilepsy gene orthologs in a mutant mouse with a low electroconvulsive threshold.</strong>
|
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Hum. Molec. Genet. 12: 975-984, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12700166/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12700166</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12700166" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddg118" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="20" class="mim-anchor"></a>
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<a id="Zhang2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhang, H., Craciun, L. C., Mirshahi, T., Rohacs, T., Lopes, C. M. B., Jin, T., Logothetis, D. E.
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<strong>PIP(2) activates KCNQ channels, and its hydrolysis underlies receptor-mediated inhibition of M currents.</strong>
|
|
Neuron 37: 963-975, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12670425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12670425</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12670425" 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/s0896-6273(03)00125-9" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="21" class="mim-anchor"></a>
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<a id="Zimprich2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zimprich, F., Ronen, G. M., Stogmann, W., Baumgartner, C., Stogmann, E., Rett, B., Pappas, C., Leppert, M., Singh, N., Anderson, V. E.
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<strong>Andreas Rett and benign familial neonatal convulsions revisited.</strong>
|
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Neurology 67: 864-866, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16966552/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16966552</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16966552" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/01.wnl.0000234066.46806.90" target="_blank">Full Text</a>]
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</p>
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</div>
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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 : 3/6/2014
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 10/18/2012<br>Patricia A. Hartz - updated : 8/2/2010<br>Cassandra L. Kniffin - updated : 4/1/2008<br>Cassandra L. Kniffin - updated : 1/9/2008<br>Cassandra L. Kniffin - updated : 7/31/2007<br>Cassandra L. Kniffin - updated : 3/2/2006<br>Cassandra L. Kniffin - updated : 2/22/2005<br>George E. Tiller - updated : 12/17/2004<br>Victor A. McKusick - updated : 10/29/2001<br>Michael B. Petersen - updated : 4/5/2001<br>Victor A. McKusick - updated : 7/20/2000<br>Victor A. McKusick - updated : 4/23/1999<br>Victor A. McKusick - updated : 12/3/1998<br>Victor A. McKusick - updated : 8/18/1998<br>Victor A. McKusick - updated : 1/13/1998
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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 : 12/30/1997
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 10/13/2020
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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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ckniffin : 10/13/2020<br>carol : 10/06/2020<br>carol : 01/18/2018<br>carol : 01/17/2018<br>alopez : 03/18/2014<br>mcolton : 3/10/2014<br>ckniffin : 3/6/2014<br>carol : 11/6/2012<br>ckniffin : 10/18/2012<br>carol : 2/10/2011<br>ckniffin : 2/9/2011<br>mgross : 8/18/2010<br>terry : 8/2/2010<br>carol : 10/5/2009<br>ckniffin : 9/11/2009<br>alopez : 10/13/2008<br>wwang : 4/14/2008<br>ckniffin : 4/1/2008<br>wwang : 1/23/2008<br>ckniffin : 1/9/2008<br>wwang : 8/20/2007<br>ckniffin : 7/31/2007<br>wwang : 3/14/2006<br>ckniffin : 3/2/2006<br>wwang : 2/25/2005<br>ckniffin : 2/23/2005<br>ckniffin : 2/22/2005<br>tkritzer : 12/17/2004<br>ckniffin : 2/5/2003<br>alopez : 11/1/2001<br>alopez : 11/1/2001<br>terry : 10/29/2001<br>terry : 10/29/2001<br>carol : 4/5/2001<br>mcapotos : 7/20/2000<br>mcapotos : 7/19/2000<br>mcapotos : 7/17/2000<br>mcapotos : 7/11/2000<br>terry : 6/14/2000<br>carol : 6/30/1999<br>mgross : 5/6/1999<br>mgross : 4/28/1999<br>terry : 4/23/1999<br>carol : 2/17/1999<br>alopez : 12/3/1998<br>terry : 12/3/1998<br>carol : 10/5/1998<br>carol : 8/18/1998<br>terry : 8/18/1998<br>alopez : 3/13/1998<br>mark : 1/14/1998<br>terry : 1/13/1998<br>alopez : 1/7/1998
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 602235
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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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POTASSIUM CHANNEL, VOLTAGE-GATED, KQT-LIKE SUBFAMILY, MEMBER 2; KCNQ2
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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POTASSIUM CHANNEL, VOLTAGE-GATED, SUBFAMILY Q, MEMBER 2
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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: KCNQ2</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>
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<em>
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Cytogenetic location: 20q13.33
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Genomic coordinates <span class="small">(GRCh38)</span> : 20:63,400,208-63,472,655 </span>
|
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</em>
|
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</strong>
|
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<span class="small">(from NCBI)</span>
|
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
|
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Inheritance
|
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</th>
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<th>
|
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="3">
|
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<span class="mim-font">
|
|
20q13.33
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</span>
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</td>
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<td>
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<span class="mim-font">
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Developmental and epileptic encephalopathy 7
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
613720
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Myokymia
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</span>
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</td>
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<td>
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<span class="mim-font">
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121200
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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|
3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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|
Seizures, benign neonatal, 1
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</span>
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</td>
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<td>
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<span class="mim-font">
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121200
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Description</strong>
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</span>
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</h4>
|
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</div>
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<span class="mim-text-font">
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<p>The KCNQ2 gene encodes a voltage-gated potassium channel that is expressed in the brain (Biervert et al., 1998). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Cloning and Expression</strong>
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</span>
|
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In the course of a search for the mutational basis of benign familial neonatal seizures (BFNS1; 121200) mapping to chromosome 20, Singh et al. (1998) identified a novel voltage-gated potassium channel gene that showed significant homology to KVLQT1 (also known as KCNQ1 and KCNA9), the chromosome 11 potassium channel gene responsible for long QT syndrome-1 (192500) and a form of Jervell and Lange-Nielsen cardioauditory syndrome (220400). A single cDNA isolated with the D20S24 probe in this region showed significant homology with KVLQT1. Singh et al. (1998) found that the KCNQ2 cDNA hybridized to transcripts of approximately 1.5, 3.8, and 9.5 kb on Northern blots made from brain. </p><p>By positional cloning from the 20q13.3 region where 1 form of benign familial neonatal seizures is known to map, Biervert et al. (1998) independently isolated the KCNQ2 gene and found that it was expressed in brain. </p><p>Yang et al. (1998) described the cloning, tissue distribution, and functional expression of KCNQ2 and KCNQ3 (602232), both of which are associated with benign neonatal epilepsy. The deduced 871-amino acid KCNQ2 protein has features of a voltage-gated potassium channel. Northern blot analysis of 8 human tissues detected an 8.5-kb KCNQ2 transcript in brain only. Within brain, highest expression of KCNQ2 was detected in cerebellar cortex, amygdala, caudate nucleus, and hippocampus. </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">
|
|
<strong>Gene Structure</strong>
|
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</span>
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</h4>
|
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</div>
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|
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<span class="mim-text-font">
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|
<p>Biervert and Steinlein (1999) determined that the KCNQ2 gene has at least 18 exons, occupying more than 50 kb of genomic DNA. Splice variants were identified. For example, in fetal brain, exon 8 was absent in all transcripts, while this exon was present in clones derived from adult brain RNA. </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">
|
|
<strong>Gene Function</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
|
<p>Biervert et al. (1998) found that expression of human KCNQ2 in Xenopus laevis oocytes led to potassium-selective currents that activated slowly with depolarization. </p><p>The M channel is a slowly activating and deactivating potassium conductance that plays a critical role in determining the subthreshold electroexcitability of neurons as well as the responsiveness to synaptic inputs. The M current was first described in peripheral sympathetic neurons, and differential expression of this conductance produces subtypes of sympathetic neurons with distinct firing patterns. The M channel is also expressed in many neurons in the central nervous system. Wang et al. (1998) showed that the KCNQ2 and KCNQ3 channel subunits can coassemble to form a channel with essentially identical biophysical properties and pharmacologic sensitivities to the native M channel and that the pattern of KCNQ2 and KCNQ3 gene expression is consistent with these genes encoding the native M channel. </p><p>Yang et al. (1998) demonstrated that KCNQ2 and KCNQ3, both of which are associated with benign neonatal epilepsy, interact functionally with each other and with KCNE1 (176261), which is mutant in a form of Jervell and Lange-Nielsen syndrome and in 1 form of long QT syndrome. </p><p>Cooper et al. (2000) provided information regarding the in vivo distribution and biochemical characteristics of human brain KCNQ2 and KCNQ3, the 2 channel subunits that form M channels when expressed in vitro, and, when mutated, cause the dominantly inherited epileptic syndrome, benign familial neonatal seizures. They found that the KCNQ2 and KCNQ3 proteins are colocalized in a somatodendritic pattern on pyramidal and polymorphic neurons in the human cortex and hippocampus. Immunoreactivity for KCNQ2, but not KCNQ3, is also prominent in some terminal fields, suggesting a presynaptic role for a distinct subgroup of M channels in the regulation of action potential propagation and neurotransmitter release. KCNQ2 and KCNQ3 could be coimmunoprecipitated from brain lysates. Further, both proteins were coassociated with tubulin (see 602529) and protein kinase A (see 176911) within a triton X-100-insoluble protein complex. Cooper et al. (2000) suggested that these studies provided a view of a signaling complex that may be important for cognitive function as well as epilepsy, and that analysis of this complex may shed light on the transduction pathway linking muscarinic acetylcholine receptor (see 118510) activation to M-channel inhibition. </p><p>By recording channel currents produced in cRNA-injected Xenopus oocytes, Zhang et al. (2003) found that phosphatidylinositol (4,5)-bisphosphate (PIP2) activated all members of the KCNQ channel family analyzed, including human KCNQ2 and heterodimers of human KCNQ2 and rat Kcnq3. Similar results were obtained with mammalian cells expressing KCNQ2 and Kcnq3. Mutation of his328-to-cys in KCNQ2 and his330-to-cys in Kcnq3 reduced or eliminated PIP2-mediated channel activation. Wortmannin, a pharmacologic inhibitor of PIP2 regeneration, slowed the recovery from PIP2 hydrolysis and decreased the sensitivity of the KCNQ2/Kcnq3 channel to PIP2. Zhang et al. (2003) concluded that PIP2 acts as a membrane-diffusible second messenger to regulate the activity of KCNQ currents. </p>
|
|
</span>
|
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Benign Familial Neonatal Seizures 1</em></strong></p><p>
|
|
In affected members of a family with benign familial neonatal seizures-1 (BFNS1; 121200), Singh et al. (1998) identified a small deletion on chromosome 20q encompassing the KCNQ2 gene. The finding was confirmed by fluorescence in situ hybridization in an affected individual who presented with seizures beginning at 3 days and had 118 generalized seizures until the age of 23 days. A single seizure was observed at 3.5 months in conjunction with an acute infection of the middle ear with fever, but no seizures were observed thereafter. Singh et al. (1998) also identified different heterozygous mutations in the KCNQ2 gene (see, e.g., 602235.0001 and 602235.0002) in additional families with BFNS1. </p><p>In a large pedigree with BFNS1, Biervert et al. (1998) found a 5-bp insertion (602235.0003) that was predicted to delete more than 300 amino acids from the C terminus of KCNQ2. Expression of the mutant channel did not yield measurable currents. Thus, impairment of potassium-dependent repolarization was indicated as the cause of this age-specific epileptic syndrome. </p><p>Dedek et al. (2001) reported a Caucasian family in which BFNS was followed later in life by myokymia, involuntary contractions of skeletal muscles (see 121200). All affected members of the family carried an arg207-to-trp mutation (R207W; 602235.0006) that neutralized a charged amino acid in the S4 voltage-sensor segment of KCNQ2. This substitution led to a shift of voltage-dependent activation of KCNQ2 and a dramatic slowing of activation upon depolarization. Myokymia was thought to result from hyperexcitability of the lower motoneuron; indeed both KCNQ2 and KCNQ3 mRNAs were detected in the anterior horn of the spinal cord where the cells of the lower motoneurons arise. Dedek et al. (2001) proposed that a difference in firing patterns between motoneurons and central neurons, combined with the drastically slowed voltage activation of the R207W mutant, explained by this particular KCNQ2 mutant caused myokymia in addition to BFNC. Wuttke et al. (2007) identified a mutation in the KCNQ2 gene (R207Q; 602235.0011) in a patient with isolated myokymia. </p><p>Heron et al. (2007) identified 3 deletions and 1 duplication of more than 1 exon of the KCNQ2 gene in 4 (44%) of 9 unrelated families with benign familial neonatal seizures who had previously tested negative for coding or splice site mutations. The changes were predicted to result in haploinsufficiency. The authors suggested that multiplex ligation-dependent probe amplification (MLPA) should be a second-tier testing strategy in candidate cases. </p><p><strong><em>Developmental and Epileptic Encephalopathy 7</em></strong></p><p>
|
|
In a boy with developmental and epileptic encephalopathy-7 (DEE7; 613720), Dedek et al. (2003) identified a heterozygous missense mutation in the KCNQ2 gene (S247W; 602235.0008). Functional expression studies showed that the S247W mutation reduced channel currents by more than 50% in homomeric KCNQ2 channels. The mutation was inherited from his mother, who had a milder phenotype with resolution of seizures in infancy and subsequent normal development. The son had onset of seizures at day 3 of life and the mother at age 1 month. Dedek et al. (2003) emphasized that some KCNQ2 mutations may be associated with a more severe phenotype than is typical for BFNS. </p><p>Weckhuysen et al. (2012) identified 7 different heterozygous mutations in the KCNQ2 gene (see, e.g., 602235.0012-602235.0014) in 8 (10%) of 80 patients with neonatal or early infantile seizures and associated psychomotor retardation. The mutations arose de novo in 7 cases; in 1 case, a severely affected patient inherited the mutation from her father, who had a milder phenotype and was mosaic for the mutation. </p><p>Saitsu et al. (2012) identified 3 different de novo missense mutations in the KCNQ2 gene (see, e.g., A265V, 602235.0015) in 3 of 12 Japanese patients with DEE and onset of seizures in the first week of life. The mutations were found by whole-exome sequencing. The findings suggested that KCNQ2 mutations may be a common cause of this disorder. Functional studies of the variants were not performed. </p><p>By high-resolution melting analysis or whole-exome sequencing of 239 patients with DEE, Kato et al. (2013) found that 12 patients carried a total of 10 heterozygous missense mutations in the KCNQ2 gene. The mutations occurred de novo in all patients except 1, who inherited the mutation from her mildly affected mother who was somatic mosaic for the mutation. Several of the mutations had previously been reported (see, e.g., A265V, 602235.0015), but functional studies were not performed. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The electroconvulsive threshold (ECT) test has been used extensively to determine the protection conferred by antiepileptic drug candidates against induced seizures in rodents. Yang et al. (2003) adopted the ECT test to screen the progeny of ethylnitrosourea-treated male C57BL/6J mice. In a small-scale screen, several mutant lines conferring a low threshold to ECT minimal clonic seizures were mapped to the telomeric region of mouse chromosome 2 in independent founder families. Genetic and physical mapping data indicated that several lines shared a single mutation, Szt1 (seizure threshold-1), consisting of a 300-kb deletion of genomic DNA involving 3 known genes. Two of these genes, Kcnq2 and Chrna4 (118504), are known to be mutated in human epilepsy families. Szt1 homozygotes and heterozygotes displayed similar phenotypes to those found in the respective Kcnq2 knockout mutant mice, suggesting that Kcnq2 haploinsufficiency may lie at the root of the Szt1 seizure sensitivity. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
|
|
|
|
</div>
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|
|
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|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>15 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 SEIZURES, BENIGN FAMILIAL NEONATAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNQ2, TYR284CYS
|
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|
|
<br />
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|
|
SNP: rs28939683,
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|
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|
|
ClinVar: RCV000007806, RCV003315290
|
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|
|
</span>
|
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</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with benign familial neonatal seizures (BFNS1; 121200), Singh et al. (1998) demonstrated a TAC-to-TGC transition converting codon 284 from tyrosine to cysteine. The family was too small to permit demonstration of linkage to chromosome 20. The mutation occurred in the pore region of the channel. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 SEIZURES, BENIGN FAMILIAL NEONATAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
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|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNQ2, ALA306THR
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs74315390,
|
|
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|
|
|
|
|
ClinVar: RCV000007807, RCV001245227, RCV001564572, RCV002264637, RCV002316186, RCV003315291
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In kindred 1705, Singh et al. (1998) demonstrated that individuals affected with benign familial neonatal seizures (BFNS1; 121200) had an ala306-to-thr (A306T) amino acid substitution in the S6 transmembrane segment. This alanine residue was conserved in all members of the Shaker, Shab, Shaw, and Shal subfamilies of potassium channels. </p>
|
|
</span>
|
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</div>
|
|
|
|
|
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 SEIZURES, BENIGN FAMILIAL NEONATAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
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|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNQ2, 5-BP INS
|
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|
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|
<br />
|
|
|
|
SNP: rs118192231,
|
|
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|
|
|
|
|
ClinVar: RCV000415727
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Biervert et al. (1998) identified an insertional mutation in the KCNQ2 gene in a large Australian Caucasian pedigree with benign familial neonatal seizures (BFNS1; 121200) previously reported by Berkovic et al. (1994). Biervert et al. (1998) found a heterozygous 5-bp insertion at the triplet encoding amino acid 534 in a segment highly conserved between KCNQ2 and KCNQ1 (607542), which is mutated in type 1 long QT syndrome (192500). The resulting frameshift was predicted to cause a premature stop, which would truncate more than 300 amino acids. Of 13 affected family members, 10 had known neonatal seizures. Two patients had afebrile seizures later, 1 of whom did not have neonatal seizures. One mutation carrier was unaffected, indicating reduced penetrance. Berkovic et al. (1994) noted the phenotypic heterogeneity in this family. </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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|
|
|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 SEIZURES, BENIGN FAMILIAL NEONATAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNQ2, 1-BP DEL, 1846T
|
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|
|
|
<br />
|
|
|
|
SNP: rs118192241,
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|
|
|
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ClinVar: RCV000678065
|
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|
|
|
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</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with benign familial neonatal seizures (BFNS1; 121200), Biervert and Steinlein (1999) identified a 1-bp deletion, 1846delT, in the KCNQ2 gene that caused a frameshift in exon 16, removing 228 amino acids from the predicted wildtype sequence and replacing them with a stretch of 283 amino acids showing a completely different sequence. The mutation was also present in the DNA sample obtained from the father but not in that from the mother. The paternal grandmother reportedly had also suffered from neonatal seizures but was not available for study. </p>
|
|
</span>
|
|
</div>
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<div>
|
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<br />
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</div>
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</div>
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|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 SEIZURES, BENIGN FAMILIAL NEONATAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNQ2, ARG214TRP
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|
|
|
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<br />
|
|
|
|
SNP: rs28939684,
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|
|
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ClinVar: RCV000007810, RCV000790713, RCV001851725, RCV003315292, RCV004786244
|
|
|
|
|
|
</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 4-generation Italian family segregating benign familial neonatal seizures (BFNS1; 121200), Miraglia Del Giudice et al. (2000) identified a 686C-T mutation in exon 3 of the KCNQ2 gene, resulting in an arg214-to-trp substitution. The mutation was found in the 8 affected members of the pedigree and in 1 unaffected subject who was an obligate carrier. The mutation occurred in the transmembrane domain S4, neutralizing one of the conserved, positively charged residues of that segment. The substitution abolished an AgeI restriction site and was not detected in 150 Italian controls. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 SEIZURES, BENIGN FAMILIAL NEONATAL, 1, AND/OR MYOKYMIA</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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KCNQ2, ARG207TRP
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<br />
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SNP: rs74315391,
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ClinVar: RCV000007811, RCV000187862, RCV000623725, RCV000636312, RCV000678084, RCV002255996, RCV003315293
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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 5 affected members of a Caucasian family with benign familial neonatal seizures and/or myokymia (see 121200), Dedek et al. (2001) identified a heterozygous C-to-T transition in exon 3 of the KCNQ2 gene, resulting in an arg207-to-trp (R207W) substitution in the fourth transmembrane domain. Three mutation carriers had BFNS with myokymia, 1 had isolated myokymia without seizures, and 1 had neonatal seizures with no clinical signs of myokymia, although electromyography demonstrated spontaneous discharges of grouped motor unit potentials. In vitro functional expression studies showed that the mutation resulted in a shift of voltage-dependent activation of KCNQ2 and a dramatic slowing of activation upon depolarization. The loss of potassium current was more severe compared to other KCNQ2 mutations and showed a dominant-negative effect. </p><p>In a patient with isolated myokymia and no history of neonatal seizures, Wuttke et al. (2007) identified an R207Q mutation (602235.0011) in the same codon as the R207W mutation. In vitro functional expression studies showed that mutant R207W and R207Q channels had large depolarizing shifts and marked slowing of activation time compared to wildtype channels. Coexpression with wildtype channels showed a dominant-negative effect reducing the current amplitude by 70% after short depolarization. </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>.0007 SEIZURES, BENIGN FAMILIAL NEONATAL, 1</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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DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 7, 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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KCNQ2, LYS526ASN
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<br />
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SNP: rs267607198,
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ClinVar: RCV000007813, RCV000678105, RCV001260874, RCV002292456
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In 4 affected members of a family with benign familial neonatal seizures (BFNS1; 121200), Borgatti et al. (2004) identified a heterozygous 1620G-A transition in the KCNQ2 gene, resulting in a lys526-to-asn (K526N) substitution in the C-terminal region of the protein. The mutation is located in a highly conserved region within alpha-helix B that is necessary for calmodulin binding. Functional expression studies showed that the K526N mutation decreased the voltage-dependence of the channel. Although 2 patients had a phenotype consistent with typical BFNS, the other 2 patients had a complex phenotype that was atypical and severe, consistent with developmental and epileptic encephalopathy (DEE7; 613720). One developed an extremely unfavorable outcome, profound mental retardation, and spastic quadriparesis. The other continued to have focal seizures until late infancy with a moderate degree of mental retardation and a mild cerebellar syndrome. Borgatti et al. (2004) noted that some patients with BFNS may experience seizures later in life or a different set of epileptic subtypes sometimes associated with severe neurologic and intellectual impairment. Overall, the clinical, genetic, and functional data did not provide a definitive explanation for the wide range of phenotypic variability observed in the described family, therefore preventing genotype-phenotype correlations. The authors postulated that the phenotypic variability could be due to the interplay of pathogenic mutations, modifier genes, and more subtle environmental factors. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0008 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 7</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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KCNQ2, SER247TRP
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<br />
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SNP: rs74315392,
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ClinVar: RCV000030664, RCV000678092, RCV001059860, RCV003441710
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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 boy with developmental and epileptic encephalopathy-7 (DEE7; 613720), Dedek et al. (2003) identified a heterozygous C-to-G transversion in exon 5 of the KCNQ2 gene, resulting in a ser247-to-trp (S247W) substitution in the fifth transmembrane residue of the protein. The mutation was not identified in 202 control chromosomes. Functional expression studies showed that the S247W mutation reduced channel currents by more than 50% in homomeric KCNQ2 channels. The mutation was inherited from his mother, who had a milder phenotype with resolution of seizures in infancy and subsequent normal development. The son had onset of seizures at day 3 of life and the mother at age 1 month. Dedek et al. (2003) emphasized that some KCNQ2 mutations may be associated with a more severe phenotype than is typical for BFNS. </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>.0009 SEIZURES, BENIGN FAMILIAL NEONATAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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KCNQ2, 10-BP DEL/1-BP INS, NT761
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<br />
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SNP: rs118192197,
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|
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ClinVar: RCV000678081, RCV002269819
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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 9 affected members of a large Italian family with benign familial neonatal seizures (BFNS1; 121200), Bassi et al. (2005) identified a heterozygous 10-bp deletion and 1-bp insertion (761del10insA) in cis in the KCNQ2 gene, resulting in a truncated N-terminal peptide of 194 residues. The resultant mutant protein lacks the S4 domain, which is critical for voltage sensing. In vitro functional expression studies showed that the mutant KCNQ2 subunit was unable to form functional homomeric potassium channels, suggesting haploinsufficiency rather than a dominant-negative effect. One affected family member developed severe epilepsy associated with mild mental retardation and persistent neurologic problems in adult life; this phenotypic variability was considered by the authors to be consistent with the fact that 10 to 15% of BFNS individuals experience seizure manifestations later in life. </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>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 SEIZURES, BENIGN FAMILIAL NEONATAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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KCNQ2, 1-BP DEL, 2127T
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<br />
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SNP: rs118192244,
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gnomAD: rs118192244,
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ClinVar: RCV000007814, RCV000187948, RCV000578304, RCV001389321
|
|
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|
</span>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with benign familial neonatal seizures (BFNS1; 121200), originally reported by Rett and Teubel (1964), Zimprich et al. (2006) identified a heterozygous 1-bp deletion (2127delT) in the last exon of the KCNQ2 gene, resulting in a replacement of the C terminus with 219 new amino acids and a protein that is 56 residues longer than the wildtype protein. Three of the 9 affected individuals later developed childhood nocturnal generalized tonic-clonic seizures; 2 of the 3 also had simple focal orofacial seizures. </p>
|
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</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>.0011 SEIZURES, BENIGN FAMILIAL NEONATAL, 1, AND/OR MYOKYMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNQ2, ARG207GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192200,
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|
|
|
|
|
|
|
ClinVar: RCV000007815, RCV000187863, RCV000678085, RCV000763453, RCV001205287, RCV003315294, RCV004732533
|
|
|
|
|
|
</span>
|
|
</div>
|
|
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|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 25-year-old Egyptian man with isolated myokymia (see 121200), Wuttke et al. (2007) identified a heterozygous G-to-A transition in the KCNQ2 gene, resulting in an arg207-to-gln (R207Q) substitution in a highly conserved residue in the voltage sensor region of the potassium channel. He had no history of neonatal seizures and no family history of epilepsy or peripheral nerve hyperexcitability. Clinically, he had permanent muscle overactivity in the distal upper extremities and small amplitude movements of the fingers, which were not disabling. However, he also reported exercise-induced cramps of both hands since childhood and 4 episodes of exercise-induced generalized muscle stiffness. EMG showed spontaneous irregular discharges consistent with myokymia. Wuttke et al. (2007) noted that a mutation in the same codon (R207W; 602235.0006) had been associated with neonatal epilepsy and/or myokymia. In vitro functional expression studies showed that mutant R207W and R207Q channels had large depolarizing shifts and marked slowing of activation time compared to wildtype channels. Coexpression with wildtype channels showed a dominant-negative effect reducing the current amplitude by 70% after short depolarization. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
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|
|
</div>
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 7</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNQ2, ARG213GLN
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000032979, RCV000187867, RCV000698323, RCV000763452, RCV002354177
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a girl with developmental and epileptic encephalopathy (DEE7; 613720), Weckhuysen et al. (2012) identified a heterozygous 638G-A transition in the KCNQ2 gene, resulting in an arg213-to-gln (R213Q) substitution at a highly conserved residue in the transmembrane domain. The mutation was not found in 276 control individuals. The patient had onset of multiple daily seizures on the second day of life, and the mother had noted jerking movements during pregnancy. The patient had poor response to treatment, but the seizures remitted at age 14 months. However, at age 2 years 10 months, she had severe psychomotor retardation, could not roll over, was nonverbal, had severe spastic quadriplegia, and some dysmorphic features. Her father, who had benign neonatal seizures and myokymia, was mosaic for the mutation, which was found in 30% of his lymphocytes. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 7</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNQ2, MET546VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397515420,
|
|
|
|
|
|
|
|
ClinVar: RCV000032980, RCV002225272
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 9-year-old boy with developmental and epileptic encephalopathy (DEE7; 613720), Weckhuysen et al. (2012) identified a de novo heterozygous 1636A-G transition in the KCNQ2 gene, resulting in a met546-to-val (M546V) substitution at a highly conserved residue in one of the calmodulin binding domains in the C-terminal region. The mutation was not found in 276 control individuals. On the third day of life, the patient had onset of multiple daily tonic seizures resistant to treatment and associated with a burst suppression pattern on EEG that evolved into multifocal epileptic activity. Seizures remitted at age 3 years and the EEG was normal at age 8. However, he had psychomotor retardation, mild spasticity, widely spaced gait, and lack of speech development. Brain imaging showed lesions in the basal ganglia and a thin posterior corpus callosum. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 7</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNQ2, GLY290ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397514582,
|
|
|
|
|
|
|
|
ClinVar: RCV000032981, RCV000498787, RCV000678147
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated patients with developmental and epileptic encephalopathy (DEE7; 613720), Weckhuysen et al. (2012) identified a de novo heterozygous 869G-A transition in the KCNQ2 gene, resulting in a gly290-to-asp (G290D) substitution at a highly conserved residue in the transmembrane domain. The mutation was not found in 276 control individuals. Both patients had onset of multiple daily tonic seizures on the second day of life, but the seizures remitted at around age 3 years. EEG studies were abnormal at first, but normalized over time. Both patients showed psychomotor retardation and were nonverbal. One had axial hypotonia and widely spaced gait, whereas the other had spastic quadriparesis. </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>.0015 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 7</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNQ2, ALA265VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587777219,
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|
|
|
|
|
|
|
ClinVar: RCV000106299, RCV000187868, RCV000578260, RCV000768250, RCV001056302, RCV001089803, RCV002316289, RCV004546432
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 3-month-old Japanese boy with developmental and epileptic encephalopathy (DEE7; 613720), Saitsu et al. (2012) identified a de novo heterozygous c.794C-T transition in the KCNQ2 gene, resulting in an ala265-to-val (A265V) substitution. The patient developed tonic spasms on the first day of life and then had intractable seizures associated with a suppression-burst pattern on EEG; he was diagnosed clinically with Ohtahara syndrome. He had delayed development and no eye pursuit. The patient was 1 of 12 probands with a similar disorder who underwent whole-exome sequencing. Functional studies were not performed. </p><p>Kato et al. (2013) identified a de novo heterozygous A265V substitution in 2 unrelated Japanese patients with DEE7. The mutations, which were found by whole-exome sequencing, were not present in 212 control exomes. Onset of seizures in both patients occurred in the early neonatal period. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
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|
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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>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bassi, M. T., Balottin, U., Panzeri, C., Piccinelli, P., Castaldo, P., Barrese, V., Soldovieri, M. V., Miceli, F., Colombo, M., Bresolin, N., Borgatti, R., Taglialatela, M.
|
|
<strong>Functional analysis of novel KCNQ2 and KCNQ3 gene variants found in a large pedigree with benign familial neonatal convulsions (BFNC).</strong>
|
|
Neurogenetics 6: 185-193, 2005.
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|
|
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|
|
[PubMed: 16235065]
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|
|
[Full Text: https://doi.org/10.1007/s10048-005-0012-2]
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|
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</p>
|
|
</li>
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|
<li>
|
|
<p class="mim-text-font">
|
|
Berkovic, S. F., Kennerson, M. L., Howell, R. A., Scheffer, I. E., Hwang, P. A., Nicholson, G. A.
|
|
<strong>Phenotypic expression of benign familial neonatal convulsions linked to chromosome 20.</strong>
|
|
Arch. Neurol. 51: 1125-1128, 1994.
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|
|
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|
|
[PubMed: 7980108]
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|
|
[Full Text: https://doi.org/10.1001/archneur.1994.00540230063014]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Biervert, C., Schroeder, B. C., Kubisch, C., Berkovic, S. F., Propping, P., Jentsch, T. J., Steinlein, O. K.
|
|
<strong>A potassium channel mutation in neonatal human epilepsy.</strong>
|
|
Science 279: 403-406, 1998.
|
|
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|
|
[PubMed: 9430594]
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|
|
[Full Text: https://doi.org/10.1126/science.279.5349.403]
|
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
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<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
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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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</body>
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</html>
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