3637 lines
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Entry
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- *608167 - POTASSIUM CHANNEL, SUBFAMILY T, MEMBER 1; KCNT1
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- OMIM
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<p>
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<span class="h4">*608167</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</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/608167">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div 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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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000107147;t=ENST00000371757" 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=57582" 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=608167" 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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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000107147;t=ENST00000371757" 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_001272003,NM_020822,XM_011518878,XM_011518879,XM_011518880,XM_011518881,XM_017014931,XM_017014932,XM_017014933,XM_024447617,XM_024447618" 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_020822" 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=608167" 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 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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<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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<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=18851&isoform_id=18851_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/KCNT1" 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/73920089,119608583,119608584,119608585,119608586,119608587,119608588,193785316,219521319,223460520,240255505,432134244,767957934,767957936,767957938,767957940,922312246,929654532,1034670734,1034670736,1034670739,1370514813,1370514815,2462625442,2462625444,2462625446,2462625448,2462625450,2462625452,2462625454,2462625456,2462625458" 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/Q5JUK3" 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 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 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=57582" 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=ENSG00000107147;t=ENST00000371757" 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=KCNT1" 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=KCNT1" 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+57582" 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/KCNT1" 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:57582" 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/57582" 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=chr9&hgg_gene=ENST00000371757.7&hgg_start=135702185&hgg_end=135795502&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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:18865" 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/kcnt1" 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=608167[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=608167[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/KCNT1/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/ENSG00000107147" 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=KCNT1" 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=KCNT1" 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=KCNT1" 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=KCNT1&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/PA38725" 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:18865" 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/FBgn0261698.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:1924627" 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/KCNT1#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:1924627" 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/57582/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=57582" 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=WBGene00004831;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-091231-1" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=KCNT1&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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608167
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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, SUBFAMILY T, MEMBER 1; KCNT1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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KIAA1422<br />
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SLACK
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=KCNT1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">KCNT1</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/9/642?start=-3&limit=10&highlight=642">9q34.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr9:135702185-135795502&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'})">9:135,702,185-135,795,502</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</div>
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<div>
|
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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<span class="hidden-sm hidden-xs pull-right">
|
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<a href="/clinicalSynopsis/table?mimNumber=614959,615005" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
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</a>
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</span>
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="2">
|
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<span class="mim-font">
|
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<a href="/geneMap/9/642?start=-3&limit=10&highlight=642">
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9q34.3
|
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</a>
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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Developmental and epileptic encephalopathy 14
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</span>
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</td>
|
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<td>
|
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<span class="mim-font">
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<a href="/entry/614959"> 614959 </a>
|
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</span>
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
|
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Epilepsy nocturnal frontal lobe, 5
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/615005"> 615005 </a>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
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<p>The KCNT1 gene encodes a sodium-activated potassium channel that is widely expressed in the nervous system. Its activity contributes to the slow hyperpolarization that follows repetitive firing. The C-terminal cytoplasmic domain interacts with a protein network, including FMRP (<a href="/entry/309550">309550</a>), suggesting additional functions (summary by <a href="#1" class="mim-tip-reference" title="Barcia, G., Fleming, M. R., Deligniere, A., Gazula, V.-R., Brown, M. R., Langouet, M., Chen, H., Kronengold, J., Abhyankar, A., Cilio, R., Nitschke, P., Kaminska, A., Boddaert, N., Casanova, J.-L., Desguerre, I., Munnich, A., Dulac, O., Kaczmarek, L. K., Colleaux, L., Nabbout, R. <strong>De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy.</strong> Nature Genet. 44: 1255-1259, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23086397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23086397</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23086397[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23086397">Barcia et al., 2012</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23086397" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By sequencing clones obtained from a size-fractionated brain cDNA library, <a href="#6" class="mim-tip-reference" title="Nagase, T., Kikuno, R., Ishikawa, K., Hirosawa, M., Ohara, O. <strong>Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro.</strong> DNA Res. 7: 65-73, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10718198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10718198</a>] [<a href="https://doi.org/10.1093/dnares/7.1.65" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10718198">Nagase et al. (2000)</a> cloned KCNT1, which they designated KIAA1422. The deduced 1,151-amino acid protein shares 94% identity with the rat Slack potassium channel subunit. RT-PCR detected moderate to high expression of KCNT1 in all tissues examined. Highest expression was detected in adult and fetal liver and brain, in spinal cord, and in most specific brain regions examined. Lowest expression was detected in skeletal muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10718198" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Barcia, G., Fleming, M. R., Deligniere, A., Gazula, V.-R., Brown, M. R., Langouet, M., Chen, H., Kronengold, J., Abhyankar, A., Cilio, R., Nitschke, P., Kaminska, A., Boddaert, N., Casanova, J.-L., Desguerre, I., Munnich, A., Dulac, O., Kaczmarek, L. K., Colleaux, L., Nabbout, R. <strong>De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy.</strong> Nature Genet. 44: 1255-1259, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23086397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23086397</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23086397[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23086397">Barcia et al. (2012)</a> found expression of the Kcnt1 gene in murine embryonic neurons in the hippocampus and cortex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23086397" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By radiation hybrid analysis, <a href="#6" class="mim-tip-reference" title="Nagase, T., Kikuno, R., Ishikawa, K., Hirosawa, M., Ohara, O. <strong>Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro.</strong> DNA Res. 7: 65-73, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10718198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10718198</a>] [<a href="https://doi.org/10.1093/dnares/7.1.65" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10718198">Nagase et al. (2000)</a> mapped the KCNT1 gene to chromosome 9. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10718198" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Stumpf, A. M. <strong>Personal Communication.</strong> Baltimore, Md. 10/20/2020."None>Stumpf (2020)</a> mapped the KCNT1 gene to chromosome 9q34.3 based on an alignment of the KCNT1 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=BC136618" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">BC136618</a>) with the genomic sequence (GRCh38).</p>
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<p>Using biochemical and electrophysiologic studies in mice, <a href="#2" class="mim-tip-reference" title="Brown, M. R., Kronengold, J., Gazula, V.-R., Chen, Y., Strumbos, J. G., Sigworth, F. J., Navaratnam, D., Kaczmarek, L. K. <strong>Fragile X mental retardation protein controls gating of the sodium-activated potassium channel Slack.</strong> Nature Neurosci. 13: 819-821, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20512134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20512134</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20512134[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nn.2563" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20512134">Brown et al. (2010)</a> found that the mRNA-binding protein FMRP (<a href="/entry/309550">309550</a>) binds to the C terminus of the Kcnt1 gene to activate the channel. The findings suggested a link between patterns of neuronal firing and changes in protein translation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20512134" 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>Developmental and Epileptic Encephalopathy 14/Malignant Migrating Partial Seizures of Infancy</em></strong></p><p>
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In 6 (50%) of 12 unrelated patients with sporadic occurrence of developmental and epileptic encephalopathy-14 (DEE14; <a href="/entry/614959">614959</a>) manifest clinically as malignant migrating partial seizures of infancy (MMPSI), <a href="#1" class="mim-tip-reference" title="Barcia, G., Fleming, M. R., Deligniere, A., Gazula, V.-R., Brown, M. R., Langouet, M., Chen, H., Kronengold, J., Abhyankar, A., Cilio, R., Nitschke, P., Kaminska, A., Boddaert, N., Casanova, J.-L., Desguerre, I., Munnich, A., Dulac, O., Kaczmarek, L. K., Colleaux, L., Nabbout, R. <strong>De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy.</strong> Nature Genet. 44: 1255-1259, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23086397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23086397</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23086397[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23086397">Barcia et al. (2012)</a> identified 4 different de novo heterozygous mutations in the KCNT1 gene (<a href="#0001">608167.0001</a>-<a href="#0004">608167.0004</a>). The first 2 mutations were identified by exome sequencing. Expression of 2 of the corresponding rat mutations in Xenopus oocytes resulted in Kcnt1-generated currents that resembled wildtype in terms of voltage dependence and kinetic behavior but had 2- to 3-fold higher amplitude compared to wildtype, consistent with a gain of function. The mutations were shown to cause constitutive activation of the Kcnt1 channel, mimicking the effects of phosphorylation of the C-terminal domain by protein kinase C (see, e.g., PRKCA; <a href="/entry/176960">176960</a>) activation. All patients had onset of refractory focal seizures and arrest of psychomotor development in the first 6 months of life. Brain MRI of some showed delayed myelination. EEG showed characteristic multifocal, migrating discharges. The findings suggested that KCNT1 is a major disease-associated gene for the MMPSI phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23086397" 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 child with DEE14 and severely delayed myelination, <a href="#8" class="mim-tip-reference" title="Vanderver, A., Simons, C., Schmidt, J. L., Pearl, P. L., Bloom, M., Lavenstein, B., Miller, D., Grimmond, S. M., Taft, R. J. <strong>Identification of a novel de novo p.Phe932Ile KCNT1 mutation in a patient with leukoencephalopathy and severe epilepsy.</strong> Pediat. Neurol. 50: 112-114, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24120652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24120652</a>] [<a href="https://doi.org/10.1016/j.pediatrneurol.2013.06.024" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24120652">Vanderver et al. (2014)</a> identified a de novo heterozygous mutation in the KCNT1 gene (F932I; <a href="#0009">608167.0009</a>). The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24120652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 unrelated girls with DEE14 manifest as malignant partial migrating seizures in infancy, <a href="#5" class="mim-tip-reference" title="Ishii, A., Shioda, M., Okumura, A., Kidokoro, H., Sakauchi, M., Shimada, S., Shimizu, T., Osawa, M., Hirose, S., Yamamoto, T. <strong>A recurrent KCNT1 mutation in two sporadic cases with malignant migrating partial seizures in infancy.</strong> Gene 531: 467-471, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24029078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24029078</a>] [<a href="https://doi.org/10.1016/j.gene.2013.08.096" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24029078">Ishii et al. (2013)</a> identified the same de novo heterozygous mutation in the KCNT1 gene (G288S; <a href="#0010">608167.0010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24029078" 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>Nocturnal Frontal Lobe Epilepsy 5</em></strong></p><p>
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In affected members of 4 unrelated families with autosomal dominant nocturnal frontal lobe epilepsy-5 (ENFL5; <a href="/entry/615005">615005</a>), <a href="#4" class="mim-tip-reference" title="Heron, S. E., Smith, K. R., Bahlo, M., Nobili, L., Kahana, E., Licchetta, L., Oliver, K. L., Mazarib, A., Afawi, Z., Korczyn, A., Plazzi, G., Petrou, S., Berkovic, S. F., Scheffer, I. E., Dibbens, L. M. <strong>Missense mutations in the sodium-gated potassium channel gene KCNT1 cause severe autosomal dominant nocturnal frontal lobe epilepsy.</strong> Nature Genet. 44: 1188-1190, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23086396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23086396</a>] [<a href="https://doi.org/10.1038/ng.2440" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23086396">Heron et al. (2012)</a> identified 4 different heterozygous mutations in the KCNT1 gene (<a href="#0005">608167.0005</a>-<a href="#0008">608167.0008</a>). The initial mutation was found after linkage analysis and whole-exome capture and sequencing in a large family previously reported by <a href="#3" class="mim-tip-reference" title="Derry, C. P., Heron, S. E., Phillips, F., Howell, S., MacMahon, J., Phillips, H. A., Duncan, J. S., Mulley, J. C., Berkovic, S. F., Scheffer, I. E. <strong>Severe autosomal dominant nocturnal frontal lobe epilepsy associated with psychiatric disorders and intellectual disability.</strong> Epilepsia 49: 2125-2129, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18479385/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18479385</a>] [<a href="https://doi.org/10.1111/j.1528-1167.2008.01652.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18479385">Derry et al. (2008)</a>. Affected individuals had childhood onset of partial motor seizures arising during sleep. Some developed behavioral/psychiatric manifestations and showed varying degrees of intellectual disability. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18479385+23086396" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000032793 OR RCV000117358 OR RCV000413614 OR RCV000805871 OR RCV002251941" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032793, RCV000117358, RCV000413614, RCV000805871, RCV002251941" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032793...</a>
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<p>In 3 unrelated patients (patients 2, 3, and 4) of French origin with developmental and epileptic encephalopathy-14 (DEE14; <a href="/entry/614959">614959</a>) manifest clinically as malignant migrating partial seizures of infancy (MMPSI), <a href="#1" class="mim-tip-reference" title="Barcia, G., Fleming, M. R., Deligniere, A., Gazula, V.-R., Brown, M. R., Langouet, M., Chen, H., Kronengold, J., Abhyankar, A., Cilio, R., Nitschke, P., Kaminska, A., Boddaert, N., Casanova, J.-L., Desguerre, I., Munnich, A., Dulac, O., Kaczmarek, L. K., Colleaux, L., Nabbout, R. <strong>De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy.</strong> Nature Genet. 44: 1255-1259, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23086397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23086397</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23086397[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23086397">Barcia et al. (2012)</a> identified a de novo heterozygous 1283G-A transition in exon 13 of the KCNT1 gene, resulting in an arg428-to-gln (R428Q) substitution at a highly conserved residue in the cytoplasmic C-terminal domain. The mutation was initially identified by exome sequencing and confirmed by Sanger sequencing in 1 patient; analysis of this gene in subsequent patients identified the same mutation in 2 other individuals with the same disorder. The mutation was not found in 200 controls or in several large control databases. Expression of the corresponding rat mutation, R409Q, in Xenopus oocytes resulted in Kcnt1-generated currents that resembled wildtype in terms of voltage dependence and kinetic behavior but had 2- to 3-fold higher amplitude compared to wildtype, consistent with a gain of function. The mutation was shown to cause constitutive activation of the Kcnt1 channel, mimicking the effects of phosphorylation of the C-terminal domain by protein kinase C (see, e.g., PRKCA, <a href="/entry/176960">176960</a>) activation. The patients had onset of seizures at 2 hours, 17 hours, and 2 months of age, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23086397" 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 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 14</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">rs397515403 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397515403;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=rs397515403" 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=rs397515403" 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=RCV000032794 OR RCV000494477 OR RCV000791441" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032794, RCV000494477, RCV000791441" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032794...</a>
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<p>In a 10-year-old boy (patient 1) of French origin with developmental and epileptic encephalopathy-14 (DEE14; <a href="/entry/614959">614959</a>) manifest clinically as MMPSI, <a href="#1" class="mim-tip-reference" title="Barcia, G., Fleming, M. R., Deligniere, A., Gazula, V.-R., Brown, M. R., Langouet, M., Chen, H., Kronengold, J., Abhyankar, A., Cilio, R., Nitschke, P., Kaminska, A., Boddaert, N., Casanova, J.-L., Desguerre, I., Munnich, A., Dulac, O., Kaczmarek, L. K., Colleaux, L., Nabbout, R. <strong>De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy.</strong> Nature Genet. 44: 1255-1259, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23086397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23086397</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23086397[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23086397">Barcia et al. (2012)</a> identified a de novo heterozygous 2800G-A transition in exon 24 of the KCNT1 gene, resulting in an ala934-to-thr (A934T) substitution at a highly conserved residue in the cytoplasmic C-terminal domain. The mutation was identified by exome sequencing and confirmed by Sanger sequencing; it was not found in 200 controls or in several large control databases. Expression of the corresponding rat mutation, A913T, in Xenopus oocytes resulted in Kcnt1-generated currents that resembled wildtype in terms of voltage dependence and kinetic behavior but had 2- to 3-fold higher amplitude compared to wildtype, consistent with a gain of function. The mutation was shown to cause constitutive activation of the Kcnt1 channel, mimicking the effects of phosphorylation of the C-terminal domain by protein kinase C (see, e.g., PRKCA; <a href="/entry/176960">176960</a>) activation. The patient had onset of seizures at 1 month of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23086397" 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 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 14</strong>
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KCNT1, ARG474HIS
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000032795 OR RCV000414268 OR RCV000546032 OR RCV000624507 OR RCV001253027 OR RCV002274887 OR RCV003390714 OR RCV004018702" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032795, RCV000414268, RCV000546032, RCV000624507, RCV001253027, RCV002274887, RCV003390714, RCV004018702" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032795...</a>
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<p>In a 6-month-old boy (patient 5) of French origin with developmental and epileptic encephalopathy-14 (DEE14; <a href="/entry/614959">614959</a>) manifest clinically as MMPSI, <a href="#1" class="mim-tip-reference" title="Barcia, G., Fleming, M. R., Deligniere, A., Gazula, V.-R., Brown, M. R., Langouet, M., Chen, H., Kronengold, J., Abhyankar, A., Cilio, R., Nitschke, P., Kaminska, A., Boddaert, N., Casanova, J.-L., Desguerre, I., Munnich, A., Dulac, O., Kaczmarek, L. K., Colleaux, L., Nabbout, R. <strong>De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy.</strong> Nature Genet. 44: 1255-1259, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23086397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23086397</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23086397[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23086397">Barcia et al. (2012)</a> identified a de novo heterozygous 1421G-A transition in exon 15 of the KCNT1 gene, resulting in an arg474-to-his (R474H) substitution at a highly conserved residue. The patient had onset of seizures at 2 weeks of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23086397" 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 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 14</strong>
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KCNT1, ILE760MET
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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> rs370521183 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs370521183;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/rs370521183?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=rs370521183" 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=rs370521183" 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=RCV000032796 OR RCV000413294" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032796, RCV000413294" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032796...</a>
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<p>In a 6-month-old girl (patient 6) of Ukrainian origin with developmental and epileptic encephalopathy-14 (DEE14; <a href="/entry/614959">614959</a>) manifest clinically as MMPSI, <a href="#1" class="mim-tip-reference" title="Barcia, G., Fleming, M. R., Deligniere, A., Gazula, V.-R., Brown, M. R., Langouet, M., Chen, H., Kronengold, J., Abhyankar, A., Cilio, R., Nitschke, P., Kaminska, A., Boddaert, N., Casanova, J.-L., Desguerre, I., Munnich, A., Dulac, O., Kaczmarek, L. K., Colleaux, L., Nabbout, R. <strong>De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy.</strong> Nature Genet. 44: 1255-1259, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23086397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23086397</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23086397[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23086397">Barcia et al. (2012)</a> identified a de novo heterozygous 2280C-G transversion in exon 20 of the KCNT1 gene, resulting in an ile760-to-met (I760M) substitution at a highly conserved residue. The patient had onset of seizures on the third day of life. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23086397" 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 EPILEPSY, NOCTURNAL FRONTAL LOBE, 5</strong>
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KCNT1, ARG928CYS
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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> rs397515405 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397515405;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/rs397515405?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=rs397515405" 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=rs397515405" 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=RCV000032797 OR RCV001044165 OR RCV001091224 OR RCV002247410 OR RCV004577943" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032797, RCV001044165, RCV001091224, RCV002247410, RCV004577943" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032797...</a>
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<p>In 6 affected members of an Australian family of British descent with autosomal dominant nocturnal frontal lobe epilepsy-5 (ENFL5; <a href="/entry/615005">615005</a>) (family B of <a href="#3" class="mim-tip-reference" title="Derry, C. P., Heron, S. E., Phillips, F., Howell, S., MacMahon, J., Phillips, H. A., Duncan, J. S., Mulley, J. C., Berkovic, S. F., Scheffer, I. E. <strong>Severe autosomal dominant nocturnal frontal lobe epilepsy associated with psychiatric disorders and intellectual disability.</strong> Epilepsia 49: 2125-2129, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18479385/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18479385</a>] [<a href="https://doi.org/10.1111/j.1528-1167.2008.01652.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18479385">Derry et al., 2008</a>), <a href="#4" class="mim-tip-reference" title="Heron, S. E., Smith, K. R., Bahlo, M., Nobili, L., Kahana, E., Licchetta, L., Oliver, K. L., Mazarib, A., Afawi, Z., Korczyn, A., Plazzi, G., Petrou, S., Berkovic, S. F., Scheffer, I. E., Dibbens, L. M. <strong>Missense mutations in the sodium-gated potassium channel gene KCNT1 cause severe autosomal dominant nocturnal frontal lobe epilepsy.</strong> Nature Genet. 44: 1188-1190, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23086396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23086396</a>] [<a href="https://doi.org/10.1038/ng.2440" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23086396">Heron et al. (2012)</a> identified a heterozygous 2782C-T transition in the KCNT1 gene, resulting in an arg928-to-cys (R928C) substitution at a highly conserved residue in the intracellular C-terminal region adjacent to an NAD(+)-binding site. The mutation, which was identified by whole-exome capture and sequencing and confirmed by Sanger sequencing, segregated with the phenotype in this family and was not identified in 111 control samples or in several large control databases. No functional studies were performed. The mean age at seizure onset was 4.6 years, and 5 of the 6 had refractory seizures and behavioral or psychiatric problems. Three had intellectual disability. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18479385+23086396" 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">rs397515406 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397515406;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=rs397515406" 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=rs397515406" 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=RCV000032798 OR RCV000813544" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032798, RCV000813544" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032798...</a>
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<p>In 4 individuals of a 3-generation Italian family with nocturnal frontal lobe epilepsy (ENFL5; <a href="/entry/615005">615005</a>), <a href="#4" class="mim-tip-reference" title="Heron, S. E., Smith, K. R., Bahlo, M., Nobili, L., Kahana, E., Licchetta, L., Oliver, K. L., Mazarib, A., Afawi, Z., Korczyn, A., Plazzi, G., Petrou, S., Berkovic, S. F., Scheffer, I. E., Dibbens, L. M. <strong>Missense mutations in the sodium-gated potassium channel gene KCNT1 cause severe autosomal dominant nocturnal frontal lobe epilepsy.</strong> Nature Genet. 44: 1188-1190, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23086396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23086396</a>] [<a href="https://doi.org/10.1038/ng.2440" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23086396">Heron et al. (2012)</a> identified a heterozygous 2386T-C transition in the KCNT1 gene, resulting in a tyr796-to-his (Y796H) substitution at a highly conserved residue in the intracellular C-terminal region adjacent to an NAD(+)-binding site. No functional studies were performed. The mean age of seizure onset was 5.5 years. Three patients had intellectual disability, and 2 had behavioral or psychiatric abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23086396" 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">rs397515407 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397515407;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=rs397515407" 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=rs397515407" 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=RCV000032799 OR RCV000412976 OR RCV000553512 OR RCV000787272 OR RCV001375627 OR RCV003398586 OR RCV004576914" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032799, RCV000412976, RCV000553512, RCV000787272, RCV001375627, RCV003398586, RCV004576914" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032799...</a>
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<p>In 4 affected individuals of an Israeli family with nocturnal frontal lobe epilepsy (ENFL5; <a href="/entry/615005">615005</a>), <a href="#4" class="mim-tip-reference" title="Heron, S. E., Smith, K. R., Bahlo, M., Nobili, L., Kahana, E., Licchetta, L., Oliver, K. L., Mazarib, A., Afawi, Z., Korczyn, A., Plazzi, G., Petrou, S., Berkovic, S. F., Scheffer, I. E., Dibbens, L. M. <strong>Missense mutations in the sodium-gated potassium channel gene KCNT1 cause severe autosomal dominant nocturnal frontal lobe epilepsy.</strong> Nature Genet. 44: 1188-1190, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23086396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23086396</a>] [<a href="https://doi.org/10.1038/ng.2440" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23086396">Heron et al. (2012)</a> identified a heterozygous 1193G-A transition in the KCNT1 gene, resulting in an arg398-to-gln (R398Q) substitution. No functional studies were performed. Two of the 4 patients had behavioral or psychiatric abnormalities, but all were cognitively normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23086396" 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">rs797044544 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs797044544;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=rs797044544" 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=rs797044544" 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=RCV000192060" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000192060" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000192060</a>
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<p>In an Australian boy of British descent with nocturnal frontal lobe epilepsy (ENFL5; <a href="/entry/615005">615005</a>), <a href="#4" class="mim-tip-reference" title="Heron, S. E., Smith, K. R., Bahlo, M., Nobili, L., Kahana, E., Licchetta, L., Oliver, K. L., Mazarib, A., Afawi, Z., Korczyn, A., Plazzi, G., Petrou, S., Berkovic, S. F., Scheffer, I. E., Dibbens, L. M. <strong>Missense mutations in the sodium-gated potassium channel gene KCNT1 cause severe autosomal dominant nocturnal frontal lobe epilepsy.</strong> Nature Genet. 44: 1188-1190, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23086396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23086396</a>] [<a href="https://doi.org/10.1038/ng.2440" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23086396">Heron et al. (2012)</a> identified a de novo heterozygous 2688G-A transition in the KCNT1 gene, resulting in a met896-to-ile (M896I) substitution at a highly conserved residue within the NAD(+)-binding site. No functional studies were performed. The patient had onset of refractory seizures at age 9 years and showed a behavioral/psychiatric disorder, but had normal intellectual function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23086396" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 14</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">rs886044717 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886044717;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=rs886044717" 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=rs886044717" 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=RCV000077799 OR RCV000650650" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000077799, RCV000650650" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000077799...</a>
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<p>In a 10-year-old boy with developmental and epileptic encephalopathy-14 (DEE14; <a href="/entry/614959">614959</a>), <a href="#8" class="mim-tip-reference" title="Vanderver, A., Simons, C., Schmidt, J. L., Pearl, P. L., Bloom, M., Lavenstein, B., Miller, D., Grimmond, S. M., Taft, R. J. <strong>Identification of a novel de novo p.Phe932Ile KCNT1 mutation in a patient with leukoencephalopathy and severe epilepsy.</strong> Pediat. Neurol. 50: 112-114, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24120652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24120652</a>] [<a href="https://doi.org/10.1016/j.pediatrneurol.2013.06.024" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24120652">Vanderver et al. (2014)</a> identified a de novo heterozygous c.2794T-A transversion in the KCNT1 gene, resulting in a phe932-to-ile (F932I) substitution at a highly conserved residue in the cytoplasmic C-terminal domain. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. It was not present in the dbSNP (build 135), 1000 Genomes Project, or Exome Sequencing Project databases. Functional studies were not performed. The patient presented at age 1 month with refractory myoclonic seizures that progressed to several different seizure types and status epilepticus. He had microcephaly and encephalopathic encephalopathy, with severe developmental stagnation. Brain imaging showed severely delayed myelination, and EEG showed background slowing with superimposed multifocal interictal sharp discharges and occasional periods of burst-suppression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24120652" 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">rs587777264 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777264;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=rs587777264" 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=rs587777264" 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=RCV000114361 OR RCV000255411 OR RCV000627792 OR RCV001265540" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000114361, RCV000255411, RCV000627792, RCV001265540" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000114361...</a>
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<p>In 2 unrelated girls with developmental and epileptic encephalopathy (DEE14; <a href="/entry/614959">614959</a>) presenting as malignant migrating partial seizures in infancy, <a href="#5" class="mim-tip-reference" title="Ishii, A., Shioda, M., Okumura, A., Kidokoro, H., Sakauchi, M., Shimada, S., Shimizu, T., Osawa, M., Hirose, S., Yamamoto, T. <strong>A recurrent KCNT1 mutation in two sporadic cases with malignant migrating partial seizures in infancy.</strong> Gene 531: 467-471, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24029078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24029078</a>] [<a href="https://doi.org/10.1016/j.gene.2013.08.096" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24029078">Ishii et al. (2013)</a> identified a de novo heterozygous c.862G-A transition in the KCNT1 gene, resulting in a gly288-to-ser (G288S) substitution at a highly conserved residue in the pore region of the channel. The mutation was not found in the dbSNP or 1000 Genomes Project databases, or in 100 control individuals. Molecular modeling predicted that the mutation may change molecular structure and impair ion channel function, but functional studies were not performed. Both patients presented with intractable seizures at 2 months of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24029078" 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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Barcia, G., Fleming, M. R., Deligniere, A., Gazula, V.-R., Brown, M. R., Langouet, M., Chen, H., Kronengold, J., Abhyankar, A., Cilio, R., Nitschke, P., Kaminska, A., Boddaert, N., Casanova, J.-L., Desguerre, I., Munnich, A., Dulac, O., Kaczmarek, L. K., Colleaux, L., Nabbout, R.
|
|
<strong>De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy.</strong>
|
|
Nature Genet. 44: 1255-1259, 2012.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23086397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23086397</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23086397[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=23086397" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1038/ng.2441" 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="2" class="mim-anchor"></a>
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<a id="Brown2010" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
|
Brown, M. R., Kronengold, J., Gazula, V.-R., Chen, Y., Strumbos, J. G., Sigworth, F. J., Navaratnam, D., Kaczmarek, L. K.
|
|
<strong>Fragile X mental retardation protein controls gating of the sodium-activated potassium channel Slack.</strong>
|
|
Nature Neurosci. 13: 819-821, 2010.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20512134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20512134</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20512134[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=20512134" 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/nn.2563" 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="3" class="mim-anchor"></a>
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<a id="Derry2008" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
|
Derry, C. P., Heron, S. E., Phillips, F., Howell, S., MacMahon, J., Phillips, H. A., Duncan, J. S., Mulley, J. C., Berkovic, S. F., Scheffer, I. E.
|
|
<strong>Severe autosomal dominant nocturnal frontal lobe epilepsy associated with psychiatric disorders and intellectual disability.</strong>
|
|
Epilepsia 49: 2125-2129, 2008.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18479385/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18479385</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18479385" 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/j.1528-1167.2008.01652.x" 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="4" class="mim-anchor"></a>
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<a id="Heron2012" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Heron, S. E., Smith, K. R., Bahlo, M., Nobili, L., Kahana, E., Licchetta, L., Oliver, K. L., Mazarib, A., Afawi, Z., Korczyn, A., Plazzi, G., Petrou, S., Berkovic, S. F., Scheffer, I. E., Dibbens, L. M.
|
|
<strong>Missense mutations in the sodium-gated potassium channel gene KCNT1 cause severe autosomal dominant nocturnal frontal lobe epilepsy.</strong>
|
|
Nature Genet. 44: 1188-1190, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23086396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23086396</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23086396" 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/ng.2440" 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="5" class="mim-anchor"></a>
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<a id="Ishii2013" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ishii, A., Shioda, M., Okumura, A., Kidokoro, H., Sakauchi, M., Shimada, S., Shimizu, T., Osawa, M., Hirose, S., Yamamoto, T.
|
|
<strong>A recurrent KCNT1 mutation in two sporadic cases with malignant migrating partial seizures in infancy.</strong>
|
|
Gene 531: 467-471, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24029078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24029078</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24029078" 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/j.gene.2013.08.096" 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="6" class="mim-anchor"></a>
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<a id="Nagase2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Nagase, T., Kikuno, R., Ishikawa, K., Hirosawa, M., Ohara, O.
|
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<strong>Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro.</strong>
|
|
DNA Res. 7: 65-73, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10718198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10718198</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10718198" 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/dnares/7.1.65" 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="7" class="mim-anchor"></a>
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<a id="Stumpf2020" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Stumpf, A. M.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 10/20/2020.
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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="8" class="mim-anchor"></a>
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<a id="Vanderver2014" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Vanderver, A., Simons, C., Schmidt, J. L., Pearl, P. L., Bloom, M., Lavenstein, B., Miller, D., Grimmond, S. M., Taft, R. J.
|
|
<strong>Identification of a novel de novo p.Phe932Ile KCNT1 mutation in a patient with leukoencephalopathy and severe epilepsy.</strong>
|
|
Pediat. Neurol. 50: 112-114, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24120652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24120652</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24120652" 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/j.pediatrneurol.2013.06.024" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Anne M. Stumpf - updated : 10/20/2020
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</span>
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</div>
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</div>
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<div class="row collapse" id="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 : 3/26/2014<br>Cassandra L. Kniffin - updated : 1/7/2014<br>Cassandra L. Kniffin - updated : 1/7/2013<br>Cassandra L. Kniffin - updated : 12/3/2012
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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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Patricia A. Hartz : 10/14/2003
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 10/20/2020
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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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joanna : 10/09/2020<br>carol : 01/17/2018<br>carol : 10/04/2016<br>carol : 06/24/2016<br>carol : 4/1/2014<br>ckniffin : 3/26/2014<br>carol : 1/8/2014<br>ckniffin : 1/7/2014<br>carol : 1/8/2013<br>ckniffin : 1/7/2013<br>terry : 12/5/2012<br>alopez : 12/4/2012<br>ckniffin : 12/3/2012<br>alopez : 4/18/2006<br>mgross : 10/14/2003
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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> 608167
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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, SUBFAMILY T, MEMBER 1; KCNT1
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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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KIAA1422<br />
|
|
SLACK
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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>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: KCNT1</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>
|
|
Cytogenetic location: 9q34.3
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 9:135,702,185-135,795,502 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</h4>
|
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<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
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</th>
|
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<th>
|
|
Phenotype
|
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</th>
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<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
9q34.3
|
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</span>
|
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</td>
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<td>
|
|
<span class="mim-font">
|
|
Developmental and epileptic encephalopathy 14
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
614959
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
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</tr>
|
|
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|
|
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|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Epilepsy nocturnal frontal lobe, 5
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
615005
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
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</tbody>
|
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</table>
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</div>
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</div>
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<div>
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<br />
|
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</div>
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<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
|
<span class="mim-text-font">
|
|
<p>The KCNT1 gene encodes a sodium-activated potassium channel that is widely expressed in the nervous system. Its activity contributes to the slow hyperpolarization that follows repetitive firing. The C-terminal cytoplasmic domain interacts with a protein network, including FMRP (309550), suggesting additional functions (summary by Barcia et al., 2012). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<span class="mim-text-font">
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<p>By sequencing clones obtained from a size-fractionated brain cDNA library, Nagase et al. (2000) cloned KCNT1, which they designated KIAA1422. The deduced 1,151-amino acid protein shares 94% identity with the rat Slack potassium channel subunit. RT-PCR detected moderate to high expression of KCNT1 in all tissues examined. Highest expression was detected in adult and fetal liver and brain, in spinal cord, and in most specific brain regions examined. Lowest expression was detected in skeletal muscle. </p><p>Barcia et al. (2012) found expression of the Kcnt1 gene in murine embryonic neurons in the hippocampus and cortex. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By radiation hybrid analysis, Nagase et al. (2000) mapped the KCNT1 gene to chromosome 9. </p><p>Stumpf (2020) mapped the KCNT1 gene to chromosome 9q34.3 based on an alignment of the KCNT1 sequence (GenBank BC136618) with the genomic sequence (GRCh38).</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using biochemical and electrophysiologic studies in mice, Brown et al. (2010) found that the mRNA-binding protein FMRP (309550) binds to the C terminus of the Kcnt1 gene to activate the channel. The findings suggested a link between patterns of neuronal firing and changes in protein translation. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Developmental and Epileptic Encephalopathy 14/Malignant Migrating Partial Seizures of Infancy</em></strong></p><p>
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|
In 6 (50%) of 12 unrelated patients with sporadic occurrence of developmental and epileptic encephalopathy-14 (DEE14; 614959) manifest clinically as malignant migrating partial seizures of infancy (MMPSI), Barcia et al. (2012) identified 4 different de novo heterozygous mutations in the KCNT1 gene (608167.0001-608167.0004). The first 2 mutations were identified by exome sequencing. Expression of 2 of the corresponding rat mutations in Xenopus oocytes resulted in Kcnt1-generated currents that resembled wildtype in terms of voltage dependence and kinetic behavior but had 2- to 3-fold higher amplitude compared to wildtype, consistent with a gain of function. The mutations were shown to cause constitutive activation of the Kcnt1 channel, mimicking the effects of phosphorylation of the C-terminal domain by protein kinase C (see, e.g., PRKCA; 176960) activation. All patients had onset of refractory focal seizures and arrest of psychomotor development in the first 6 months of life. Brain MRI of some showed delayed myelination. EEG showed characteristic multifocal, migrating discharges. The findings suggested that KCNT1 is a major disease-associated gene for the MMPSI phenotype. </p><p>In a child with DEE14 and severely delayed myelination, Vanderver et al. (2014) identified a de novo heterozygous mutation in the KCNT1 gene (F932I; 608167.0009). The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. </p><p>In 2 unrelated girls with DEE14 manifest as malignant partial migrating seizures in infancy, Ishii et al. (2013) identified the same de novo heterozygous mutation in the KCNT1 gene (G288S; 608167.0010). </p><p><strong><em>Nocturnal Frontal Lobe Epilepsy 5</em></strong></p><p>
|
|
In affected members of 4 unrelated families with autosomal dominant nocturnal frontal lobe epilepsy-5 (ENFL5; 615005), Heron et al. (2012) identified 4 different heterozygous mutations in the KCNT1 gene (608167.0005-608167.0008). The initial mutation was found after linkage analysis and whole-exome capture and sequencing in a large family previously reported by Derry et al. (2008). Affected individuals had childhood onset of partial motor seizures arising during sleep. Some developed behavioral/psychiatric manifestations and showed varying degrees of intellectual disability. </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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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>10 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 14</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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KCNT1, ARG428GLN
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<br />
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ClinVar: RCV000032793, RCV000117358, RCV000413614, RCV000805871, RCV002251941
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In 3 unrelated patients (patients 2, 3, and 4) of French origin with developmental and epileptic encephalopathy-14 (DEE14; 614959) manifest clinically as malignant migrating partial seizures of infancy (MMPSI), Barcia et al. (2012) identified a de novo heterozygous 1283G-A transition in exon 13 of the KCNT1 gene, resulting in an arg428-to-gln (R428Q) substitution at a highly conserved residue in the cytoplasmic C-terminal domain. The mutation was initially identified by exome sequencing and confirmed by Sanger sequencing in 1 patient; analysis of this gene in subsequent patients identified the same mutation in 2 other individuals with the same disorder. The mutation was not found in 200 controls or in several large control databases. Expression of the corresponding rat mutation, R409Q, in Xenopus oocytes resulted in Kcnt1-generated currents that resembled wildtype in terms of voltage dependence and kinetic behavior but had 2- to 3-fold higher amplitude compared to wildtype, consistent with a gain of function. The mutation was shown to cause constitutive activation of the Kcnt1 channel, mimicking the effects of phosphorylation of the C-terminal domain by protein kinase C (see, e.g., PRKCA, 176960) activation. The patients had onset of seizures at 2 hours, 17 hours, and 2 months of age, respectively. </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>.0002 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 14</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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KCNT1, ALA934THR
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<br />
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SNP: rs397515403,
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ClinVar: RCV000032794, RCV000494477, RCV000791441
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a 10-year-old boy (patient 1) of French origin with developmental and epileptic encephalopathy-14 (DEE14; 614959) manifest clinically as MMPSI, Barcia et al. (2012) identified a de novo heterozygous 2800G-A transition in exon 24 of the KCNT1 gene, resulting in an ala934-to-thr (A934T) substitution at a highly conserved residue in the cytoplasmic C-terminal domain. The mutation was identified by exome sequencing and confirmed by Sanger sequencing; it was not found in 200 controls or in several large control databases. Expression of the corresponding rat mutation, A913T, in Xenopus oocytes resulted in Kcnt1-generated currents that resembled wildtype in terms of voltage dependence and kinetic behavior but had 2- to 3-fold higher amplitude compared to wildtype, consistent with a gain of function. The mutation was shown to cause constitutive activation of the Kcnt1 channel, mimicking the effects of phosphorylation of the C-terminal domain by protein kinase C (see, e.g., PRKCA; 176960) activation. The patient had onset of seizures at 1 month of age. </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 14</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNT1, ARG474HIS
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<br />
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|
|
ClinVar: RCV000032795, RCV000414268, RCV000546032, RCV000624507, RCV001253027, RCV002274887, RCV003390714, RCV004018702
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-month-old boy (patient 5) of French origin with developmental and epileptic encephalopathy-14 (DEE14; 614959) manifest clinically as MMPSI, Barcia et al. (2012) identified a de novo heterozygous 1421G-A transition in exon 15 of the KCNT1 gene, resulting in an arg474-to-his (R474H) substitution at a highly conserved residue. The patient had onset of seizures at 2 weeks of age. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
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|
<br />
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|
</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 14</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNT1, ILE760MET
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs370521183,
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|
|
|
|
|
gnomAD: rs370521183,
|
|
|
|
|
|
ClinVar: RCV000032796, RCV000413294
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-month-old girl (patient 6) of Ukrainian origin with developmental and epileptic encephalopathy-14 (DEE14; 614959) manifest clinically as MMPSI, Barcia et al. (2012) identified a de novo heterozygous 2280C-G transversion in exon 20 of the KCNT1 gene, resulting in an ile760-to-met (I760M) substitution at a highly conserved residue. The patient had onset of seizures on the third day of life. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 EPILEPSY, NOCTURNAL FRONTAL LOBE, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNT1, ARG928CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397515405,
|
|
|
|
|
|
gnomAD: rs397515405,
|
|
|
|
|
|
ClinVar: RCV000032797, RCV001044165, RCV001091224, RCV002247410, RCV004577943
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 6 affected members of an Australian family of British descent with autosomal dominant nocturnal frontal lobe epilepsy-5 (ENFL5; 615005) (family B of Derry et al., 2008), Heron et al. (2012) identified a heterozygous 2782C-T transition in the KCNT1 gene, resulting in an arg928-to-cys (R928C) substitution at a highly conserved residue in the intracellular C-terminal region adjacent to an NAD(+)-binding site. The mutation, which was identified by whole-exome capture and sequencing and confirmed by Sanger sequencing, segregated with the phenotype in this family and was not identified in 111 control samples or in several large control databases. No functional studies were performed. The mean age at seizure onset was 4.6 years, and 5 of the 6 had refractory seizures and behavioral or psychiatric problems. Three had intellectual disability. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 EPILEPSY, NOCTURNAL FRONTAL LOBE, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNT1, TYR796HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397515406,
|
|
|
|
|
|
|
|
ClinVar: RCV000032798, RCV000813544
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 individuals of a 3-generation Italian family with nocturnal frontal lobe epilepsy (ENFL5; 615005), Heron et al. (2012) identified a heterozygous 2386T-C transition in the KCNT1 gene, resulting in a tyr796-to-his (Y796H) substitution at a highly conserved residue in the intracellular C-terminal region adjacent to an NAD(+)-binding site. No functional studies were performed. The mean age of seizure onset was 5.5 years. Three patients had intellectual disability, and 2 had behavioral or psychiatric abnormalities. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 EPILEPSY, NOCTURNAL FRONTAL LOBE, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNT1, ARG398GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397515407,
|
|
|
|
|
|
|
|
ClinVar: RCV000032799, RCV000412976, RCV000553512, RCV000787272, RCV001375627, RCV003398586, RCV004576914
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 affected individuals of an Israeli family with nocturnal frontal lobe epilepsy (ENFL5; 615005), Heron et al. (2012) identified a heterozygous 1193G-A transition in the KCNT1 gene, resulting in an arg398-to-gln (R398Q) substitution. No functional studies were performed. Two of the 4 patients had behavioral or psychiatric abnormalities, but all were cognitively normal. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 EPILEPSY, NOCTURNAL FRONTAL LOBE, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNT1, MET896ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs797044544,
|
|
|
|
|
|
|
|
ClinVar: RCV000192060
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Australian boy of British descent with nocturnal frontal lobe epilepsy (ENFL5; 615005), Heron et al. (2012) identified a de novo heterozygous 2688G-A transition in the KCNT1 gene, resulting in a met896-to-ile (M896I) substitution at a highly conserved residue within the NAD(+)-binding site. No functional studies were performed. The patient had onset of refractory seizures at age 9 years and showed a behavioral/psychiatric disorder, but had normal intellectual function. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 14</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNT1, PHE932ILE
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|
|
|
|
|
<br />
|
|
|
|
SNP: rs886044717,
|
|
|
|
|
|
|
|
ClinVar: RCV000077799, RCV000650650
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 10-year-old boy with developmental and epileptic encephalopathy-14 (DEE14; 614959), Vanderver et al. (2014) identified a de novo heterozygous c.2794T-A transversion in the KCNT1 gene, resulting in a phe932-to-ile (F932I) substitution at a highly conserved residue in the cytoplasmic C-terminal domain. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. It was not present in the dbSNP (build 135), 1000 Genomes Project, or Exome Sequencing Project databases. Functional studies were not performed. The patient presented at age 1 month with refractory myoclonic seizures that progressed to several different seizure types and status epilepticus. He had microcephaly and encephalopathic encephalopathy, with severe developmental stagnation. Brain imaging showed severely delayed myelination, and EEG showed background slowing with superimposed multifocal interictal sharp discharges and occasional periods of burst-suppression. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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<div>
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 14</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNT1, GLY288SER
|
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|
|
<br />
|
|
|
|
SNP: rs587777264,
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|
|
|
|
|
ClinVar: RCV000114361, RCV000255411, RCV000627792, RCV001265540
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated girls with developmental and epileptic encephalopathy (DEE14; 614959) presenting as malignant migrating partial seizures in infancy, Ishii et al. (2013) identified a de novo heterozygous c.862G-A transition in the KCNT1 gene, resulting in a gly288-to-ser (G288S) substitution at a highly conserved residue in the pore region of the channel. The mutation was not found in the dbSNP or 1000 Genomes Project databases, or in 100 control individuals. Molecular modeling predicted that the mutation may change molecular structure and impair ion channel function, but functional studies were not performed. Both patients presented with intractable seizures at 2 months of age. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
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<span class="mim-font">
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<strong>REFERENCES</strong>
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Barcia, G., Fleming, M. R., Deligniere, A., Gazula, V.-R., Brown, M. R., Langouet, M., Chen, H., Kronengold, J., Abhyankar, A., Cilio, R., Nitschke, P., Kaminska, A., Boddaert, N., Casanova, J.-L., Desguerre, I., Munnich, A., Dulac, O., Kaczmarek, L. K., Colleaux, L., Nabbout, R.
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<strong>De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy.</strong>
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Nature Genet. 44: 1255-1259, 2012.
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[PubMed: 23086397]
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[Full Text: https://doi.org/10.1038/ng.2441]
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Brown, M. R., Kronengold, J., Gazula, V.-R., Chen, Y., Strumbos, J. G., Sigworth, F. J., Navaratnam, D., Kaczmarek, L. K.
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<strong>Fragile X mental retardation protein controls gating of the sodium-activated potassium channel Slack.</strong>
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Nature Neurosci. 13: 819-821, 2010.
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[PubMed: 20512134]
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<p class="mim-text-font">
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Derry, C. P., Heron, S. E., Phillips, F., Howell, S., MacMahon, J., Phillips, H. A., Duncan, J. S., Mulley, J. C., Berkovic, S. F., Scheffer, I. E.
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<strong>Severe autosomal dominant nocturnal frontal lobe epilepsy associated with psychiatric disorders and intellectual disability.</strong>
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Epilepsia 49: 2125-2129, 2008.
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</p>
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<li>
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<p class="mim-text-font">
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Heron, S. E., Smith, K. R., Bahlo, M., Nobili, L., Kahana, E., Licchetta, L., Oliver, K. L., Mazarib, A., Afawi, Z., Korczyn, A., Plazzi, G., Petrou, S., Berkovic, S. F., Scheffer, I. E., Dibbens, L. M.
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<strong>Missense mutations in the sodium-gated potassium channel gene KCNT1 cause severe autosomal dominant nocturnal frontal lobe epilepsy.</strong>
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Nature Genet. 44: 1188-1190, 2012.
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[PubMed: 23086396]
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[Full Text: https://doi.org/10.1038/ng.2440]
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</p>
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<li>
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<p class="mim-text-font">
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Ishii, A., Shioda, M., Okumura, A., Kidokoro, H., Sakauchi, M., Shimada, S., Shimizu, T., Osawa, M., Hirose, S., Yamamoto, T.
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<strong>A recurrent KCNT1 mutation in two sporadic cases with malignant migrating partial seizures in infancy.</strong>
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Gene 531: 467-471, 2013.
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[PubMed: 24029078]
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[Full Text: https://doi.org/10.1016/j.gene.2013.08.096]
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<p class="mim-text-font">
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Nagase, T., Kikuno, R., Ishikawa, K., Hirosawa, M., Ohara, O.
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<strong>Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro.</strong>
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DNA Res. 7: 65-73, 2000.
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[PubMed: 10718198]
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[Full Text: https://doi.org/10.1093/dnares/7.1.65]
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</li>
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<li>
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<p class="mim-text-font">
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Stumpf, A. M.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 10/20/2020.
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</li>
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Vanderver, A., Simons, C., Schmidt, J. L., Pearl, P. L., Bloom, M., Lavenstein, B., Miller, D., Grimmond, S. M., Taft, R. J.
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<strong>Identification of a novel de novo p.Phe932Ile KCNT1 mutation in a patient with leukoencephalopathy and severe epilepsy.</strong>
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Pediat. Neurol. 50: 112-114, 2014.
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[PubMed: 24120652]
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[Full Text: https://doi.org/10.1016/j.pediatrneurol.2013.06.024]
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Anne M. Stumpf - updated : 10/20/2020<br>Cassandra L. Kniffin - updated : 3/26/2014<br>Cassandra L. Kniffin - updated : 1/7/2014<br>Cassandra L. Kniffin - updated : 1/7/2013<br>Cassandra L. Kniffin - updated : 12/3/2012
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Patricia A. Hartz : 10/14/2003
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