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Entry
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- *604619 - LEUCINE-RICH GENE, GLIOMA-INACTIVATED, 1; LGI1
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*604619</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/604619">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000108231;t=ENST00000371418" 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=9211" 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=604619" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000108231;t=ENST00000371418" 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_001308275,NM_001308276,NM_005097,NR_131777,XM_017016911,XM_017016912" 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_005097" 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=604619" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=05216&isoform_id=05216_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/LGI1" 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/4091819,4826816,18490910,20452372,32469669,37182888,62088396,63089590,119570436,119570437,119570438,158260435,194384218,815891250,815891253,957950607,957950610,957950613,957950616,1034570286,1034570288,2462521842,2462521844" 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/O95970" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=9211" 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=ENSG00000108231;t=ENST00000371418" 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=LGI1" 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=LGI1" 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+9211" 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/LGI1" 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:9211" 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/9211" 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=chr10&hgg_gene=ENST00000371418.9&hgg_start=93757936&hgg_end=93798159&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:6572" 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/lgi1" 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=604619[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=604619[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/LGI1/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/ENSG00000108231" 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=LGI1" 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=LGI1" 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=LGI1" 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=LGI1&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/PA30349" 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:6572" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1861691" 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/LGI1#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:1861691" 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/9211/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=9211" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-030131-1731" 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=LGI1&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 784377008<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
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604619
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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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LEUCINE-RICH GENE, GLIOMA-INACTIVATED, 1; LGI1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
|
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
EPITEMPIN; EPTP
|
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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">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=LGI1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">LGI1</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/10/411?start=-3&limit=10&highlight=411">10q23.33</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr10:93757936-93798159&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'})">10:93,757,936-93,798,159</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
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</div>
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<div>
|
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</div>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
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<th>
|
|
Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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|
Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
|
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Phenotype <br /> mapping key
|
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
|
<a href="/geneMap/10/411?start=-3&limit=10&highlight=411">
|
|
10q23.33
|
|
</a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Epilepsy, familial temporal lobe, 1
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/600512"> 600512 </a>
|
|
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="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">
|
|
<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;">
|
|
<li><a href="/graph/linear/604619" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/604619" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</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="text" class="mim-anchor"></a>
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<h4>
|
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|
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<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
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</span>
|
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</h4>
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<div>
|
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<a id="description" class="mim-anchor"></a>
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<p>The LGI1 gene encodes a secreted leucine-rich protein that is expressed in brain and plays a role in regulating postnatal glutamatergic synapse development (summary by <a href="#1" class="mim-tip-reference" title="Anderson, M. P. <strong>Arrested glutamatergic synapse development in human partial epilepsy.</strong> Epilepsy Curr. 10: 153-158, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21157544/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21157544</a>] [<a href="https://doi.org/10.1111/j.1535-7511.2010.01386.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21157544">Anderson, 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21157544" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="Chernova, O. B., Somerville, R. P. T., Cowell, J. K. <strong>A novel gene, LGI1, from 10q24 is rearranged and downregulated in malignant brain tumors.</strong> Oncogene 17: 2873-2881, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9879993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9879993</a>] [<a href="https://doi.org/10.1038/sj.onc.1202481" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9879993">Chernova et al. (1998)</a> used a positional cloning strategy to isolate LGI1, which they found was rearranged as a result of a t(10;19)(q24;q13) balanced translocation in a glioblastoma (<a href="/entry/137800">137800</a>) cell line (T98G). The LGI1 cDNA predicts a precursor protein with 557 amino acids and a calculated molecular mass of 64 kD. After the cleavage of the signal peptide, the mature LGI1 protein is 60 kD. The protein contains a hydrophobic segment representing a putative transmembrane domain, with the amino terminus located outside the cell. It also contains 3.5 leucine-rich repeats (LRR) with conserved cysteine-rich flanking sequences. In the LRR domain, LGI1 shows high homology with a number of transmembrane and extracellular proteins that function as receptors and adhesion proteins. LGI1 is predominantly expressed in neural tissues, especially in brain; its expression is reduced in low-grade brain tumors and significantly reduced or absent in malignant gliomas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9879993" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Morante-Redolat, J. M., Gorostidi-Pagola, A., Piquer-Sirerol, S., Saenz, A., Poza, J. J., Galan, J., Gesk, S., Sarafidou, T., Mautner, V.-F., Binelli, S., Staub, E., Hinzmann, B., and 15 others. <strong>Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy.</strong> Hum. Molec. Genet. 11: 1119-1128, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11978770/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11978770</a>] [<a href="https://doi.org/10.1093/hmg/11.9.1119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11978770">Morante-Redolat et al. (2002)</a> reported alternative splicing of exon 8, which appeared to vary between brain and skeletal muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11978770" 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>Most genes mutated in hereditary idiopathic epilepsies encode subunits of ion channels. Two apparent exceptions to this rule are the MASS1 gene (GPR98; <a href="/entry/602851">602851</a>), which is mutated in the Frings mouse model of audiogenic epilepsy, and LGI1. <a href="#20" class="mim-tip-reference" title="Scheel, H., Tomiuk, S., Hofmann, K. <strong>A common protein interaction domain links two recently identified epilepsy genes.</strong> Hum. Molec. Genet. 11: 1757-1762, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12095917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12095917</a>] [<a href="https://doi.org/10.1093/hmg/11.15.1757" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12095917">Scheel et al. (2002)</a> determined by amino acid analysis of both proteins that each contains a novel homology domain consisting of 7 repeats, each consisting of a 44-residue EAR (epilepsy-associated repeat) domain. The architecture and structural features of the EAR domain make it a likely member of the growing class of protein interaction domains with a 7-bladed beta-propeller fold. In the MASS1 gene product, which is a fragment of the very large G protein-coupled receptor VLGR1, the EAR domain is part of the ligand-binding ectodomain. LGI1, as well as a number of newly identified LGI1 relatives, is predicted to be a secreted protein, and consists of an N-terminal leucine-rich repeat region and a C-terminal EAR region. The human genome encodes at least 6 EAR proteins, some of which map to chromosomal regions associated with seizure disorders. <a href="#20" class="mim-tip-reference" title="Scheel, H., Tomiuk, S., Hofmann, K. <strong>A common protein interaction domain links two recently identified epilepsy genes.</strong> Hum. Molec. Genet. 11: 1757-1762, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12095917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12095917</a>] [<a href="https://doi.org/10.1093/hmg/11.15.1757" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12095917">Scheel et al. (2002)</a> hypothesized that the EAR domain may play an important role in the pathogenesis of epilepsy, either by binding to an unknown antiepileptic ligand or by interfering with axon guidance or synaptogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12095917" 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="#23" class="mim-tip-reference" title="Sirerol-Piquer, M. S., Ayerdi-Izquierdo, A., Morante-Redolat, J. M., Herranz-Perez, V., Favell, K., Barker, P. A., Perez-Tur, J. <strong>The epilepsy gene LGI1 encodes a secreted glycoprotein that binds to the cell surface.</strong> Hum. Molec. Genet. 15: 3436-3445, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17067999/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17067999</a>] [<a href="https://doi.org/10.1093/hmg/ddl421" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17067999">Sirerol-Piquer et al. (2006)</a> referred to the 7 tandem repeats of the LGI1 EAR domain as EPTP repeats. They reported that LGI1 also has 3 putative N-glycosylation sites. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17067999" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Senechal, K. R., Thaller, C., Noebels, J. L. <strong>ADPEAF mutations reduce levels of secreted LGI1, a putative tumor suppressor protein linked to epilepsy.</strong> Hum. Molec. Genet. 14: 1613-1620, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15857855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15857855</a>] [<a href="https://doi.org/10.1093/hmg/ddi169" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15857855">Senechal et al. (2005)</a> showed that Lgi1 was secreted in transfected 293T cells. In situ hybridization of adult mouse brain showed that Lgi1 mRNA is intensely expressed in granule cells of the dentate gyrus and the CA3-CA1 pyramidal cell layer of the hippocampus, with diffuse staining of the neocortex and other brain regions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15857855" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#18" class="mim-tip-reference" title="Nobile, C., Michelucci, R., Andreazza, S., Pasini, E., Tosatto, S. C. E., Striano, P. <strong>LGI1 mutations in autosomal dominant and sporadic lateral temporal epilepsy.</strong> Hum. Mutat. 30: 530-536, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19191227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19191227</a>] [<a href="https://doi.org/10.1002/humu.20925" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19191227">Nobile et al. (2009)</a> noted that the LGI1 gene contains 8 exons spanning 39.6 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19191227" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="Chernova, O. B., Somerville, R. P. T., Cowell, J. K. <strong>A novel gene, LGI1, from 10q24 is rearranged and downregulated in malignant brain tumors.</strong> Oncogene 17: 2873-2881, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9879993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9879993</a>] [<a href="https://doi.org/10.1038/sj.onc.1202481" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9879993">Chernova et al. (1998)</a> mapped the LGI1 gene to chromosome 10q24. <a href="#18" class="mim-tip-reference" title="Nobile, C., Michelucci, R., Andreazza, S., Pasini, E., Tosatto, S. C. E., Striano, P. <strong>LGI1 mutations in autosomal dominant and sporadic lateral temporal epilepsy.</strong> Hum. Mutat. 30: 530-536, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19191227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19191227</a>] [<a href="https://doi.org/10.1002/humu.20925" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19191227">Nobile et al. (2009)</a> stated that the LGI1 gene maps to chromosome 10q23.33. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19191227+9879993" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="Chernova, O. B., Somerville, R. P. T., Cowell, J. K. <strong>A novel gene, LGI1, from 10q24 is rearranged and downregulated in malignant brain tumors.</strong> Oncogene 17: 2873-2881, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9879993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9879993</a>] [<a href="https://doi.org/10.1038/sj.onc.1202481" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9879993">Chernova et al. (1998)</a> found that the LGI1 gene was rearranged as a result of a t(10;19)(q24;q13) balanced translocation in a glioblastoma (<a href="/entry/137800">137800</a>) cell line (T98G). They suggested that the localization of LGI1 to the 10q24 region and its rearrangement or inactivation in malignant brain tumors make it a strong candidate tumor suppressor gene involved in the malignant progression of glial tumors. The study was performed because previous studies had found that loss of 1 copy of chromosome 10 is a common event in high-grade gliomas; rearrangement and loss of at least some parts of the second copy, especially in the 10q23-q26 region, had been demonstrated in approximately 80% of glioblastoma multiforme tumors (<a href="#2" class="mim-tip-reference" title="Bigner, S. H., Vogelstein, B. <strong>Cytogenetics and molecular genetics of malignant gliomas and medulloblastoma.</strong> Brain Path. 1: 12-18, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1669688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1669688</a>] [<a href="https://doi.org/10.1111/j.1750-3639.1990.tb00633.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1669688">Bigner and Vogelstein, 1990</a>). <a href="#5" class="mim-tip-reference" title="Chernova, O. B., Somerville, R. P. T., Cowell, J. K. <strong>A novel gene, LGI1, from 10q24 is rearranged and downregulated in malignant brain tumors.</strong> Oncogene 17: 2873-2881, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9879993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9879993</a>] [<a href="https://doi.org/10.1038/sj.onc.1202481" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9879993">Chernova et al. (1998)</a> also detected rearrangement of the LGI1 gene in the A172 glioblastoma cell line and several glioblastoma tumors, resulting in complete absence of LGI1 expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1669688+9879993" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By semiquantitative PCR, <a href="#11" class="mim-tip-reference" title="Gu, W., Wevers, A., Schroder, H., Grzeschik, K.-H., Derst, C., Brodtkorb, E., de Vos, R., Steinlein, O. K. <strong>The LGI1 gene involved in lateral temporal lobe epilepsy belongs to a new subfamily of leucine-rich repeat proteins.</strong> FEBS Lett. 519: 71-76, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12023020/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12023020</a>] [<a href="https://doi.org/10.1016/s0014-5793(02)02713-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12023020">Gu et al. (2002)</a> detected expression of LGI1 in all tissues examined, with highest expression in brain. Immunolocalization revealed LGI1-immunoreactive neurons in all layers of the frontal and temporal cortex, with strongest labeling in layers II/III. Most of the labeled neurons displayed a pyramidal shape. Staining was detected within the perikaryon and occasionally in apical and basal dendrites, but not in nuclei. Similar labeling was found in all cortices investigated, but the intensities showed slight variations. The T98G glioblastoma cell line shows loss of LGI1 expression, and reexpression of LGI1 inhibits proliferation, invasiveness, and anchorage-independent growth. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12023020" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using gene expression arrays, <a href="#15" class="mim-tip-reference" title="Kunapuli, P., Kasyapa, C. S., Hawthorn, L., Cowell, J. K. <strong>LGI1, a putative tumor metastasis suppressor gene, controls in vitro invasiveness and expression of matrix metalloproteinases in glioma cells through the ERK1/2 pathway.</strong> J. Biol. Chem. 279: 23151-23157, 2004. Note: Erratum: J. Biol. Chem. 282: 2752 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15047712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15047712</a>] [<a href="https://doi.org/10.1074/jbc.M314192200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15047712">Kunapuli et al. (2004)</a> showed that forced reexpression of LGI1 in T98G cells resulted in downregulation of several metalloproteases, in particular MMP1 (<a href="/entry/120353">120353</a>) and MMP3 (<a href="/entry/185250">185250</a>). LGI1 expression also resulted in inhibition of ERK1 (MAPK3; <a href="/entry/601795">601795</a>) and ERK2 (MAPK1; <a href="/entry/176948">176948</a>) phosphorylation, but not p38 (MAPK14; <a href="/entry/600289">600289</a>) phosphorylation. <a href="#15" class="mim-tip-reference" title="Kunapuli, P., Kasyapa, C. S., Hawthorn, L., Cowell, J. K. <strong>LGI1, a putative tumor metastasis suppressor gene, controls in vitro invasiveness and expression of matrix metalloproteinases in glioma cells through the ERK1/2 pathway.</strong> J. Biol. Chem. 279: 23151-23157, 2004. Note: Erratum: J. Biol. Chem. 282: 2752 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15047712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15047712</a>] [<a href="https://doi.org/10.1074/jbc.M314192200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15047712">Kunapuli et al. (2004)</a> concluded that LGI1 plays a major role in suppressing production of metalloproteases through the ERK signaling pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15047712" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Gu, W., Brodtkorb, E., Piepoli, T., Finocchiaro, G., Steinlein, O. K. <strong>LGI1: a gene involved in epileptogenesis and glioma progression?</strong> Neurogenetics 6: 59-66, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15827762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15827762</a>] [<a href="https://doi.org/10.1007/s10048-005-0216-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15827762">Gu et al. (2005)</a> provided a detailed review of the LGI1 gene and concluded that the evidence supporting its role in malignant gliomas is weak. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15827762" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Fukata, Y., Adesnik, H., Iwanaga, T., Bredt, D. S., Nicoll, R. A., Fukata, M. <strong>Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission.</strong> Science 313: 1792-1795, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16990550/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16990550</a>] [<a href="https://doi.org/10.1126/science.1129947" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16990550">Fukata et al. (2006)</a> showed that ADAM22 (<a href="/entry/603709">603709</a>) serves as a receptor for LGI1. LGI1 enhances AMPA receptor-mediated synaptic transmission in hippocampal slices. The mutated form of LGI1 failed to bind to ADAM22. ADAM22 is anchored in the postsynaptic density by cytoskeletal scaffolds containing stargazin (<a href="/entry/602911">602911</a>). <a href="#8" class="mim-tip-reference" title="Fukata, Y., Adesnik, H., Iwanaga, T., Bredt, D. S., Nicoll, R. A., Fukata, M. <strong>Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission.</strong> Science 313: 1792-1795, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16990550/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16990550</a>] [<a href="https://doi.org/10.1126/science.1129947" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16990550">Fukata et al. (2006)</a> found that the interaction of ADAM22 and LGI1 with PSD95 (<a href="/entry/602887">602887</a>) was specific, as PSD95 and LGI1 quantitatively coimmunoprecipitated with ADAM22. Because PSD95 controls synaptic AMPA receptor number, <a href="#8" class="mim-tip-reference" title="Fukata, Y., Adesnik, H., Iwanaga, T., Bredt, D. S., Nicoll, R. A., Fukata, M. <strong>Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission.</strong> Science 313: 1792-1795, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16990550/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16990550</a>] [<a href="https://doi.org/10.1126/science.1129947" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16990550">Fukata et al. (2006)</a> asked whether application of LGI1 to hippocampal slices would influence glutaminergic transmission. Incubation of hippocampal slices in LGI1-AP media significantly increased the synaptic AMPA/NMDA ratio; nontagged LGI1 showed a similar effect. <a href="#8" class="mim-tip-reference" title="Fukata, Y., Adesnik, H., Iwanaga, T., Bredt, D. S., Nicoll, R. A., Fukata, M. <strong>Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission.</strong> Science 313: 1792-1795, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16990550/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16990550</a>] [<a href="https://doi.org/10.1126/science.1129947" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16990550">Fukata et al. (2006)</a> concluded that their study established a neuronal ligand-receptor interaction between LGI1 and ADAM22, both of which are genetically related to epilepsy. This study also identified LGI1 as an extracellular factor that controls synaptic strength at the excitatory synapses. Stargazin controls the trafficking and gating of AMPA receptors,0j and PSD95 anchors the AMPA receptor/stargazin complex at postsynaptic sites. Because the ADAM22 and stargazin binding sites on PSD95 do not overlap, the LGI1/ADAM22 complex may stabilize the AMPA receptor/stargazin complex on the PSD95 scaffolding platform. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16990550" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using mutation analysis, <a href="#23" class="mim-tip-reference" title="Sirerol-Piquer, M. S., Ayerdi-Izquierdo, A., Morante-Redolat, J. M., Herranz-Perez, V., Favell, K., Barker, P. A., Perez-Tur, J. <strong>The epilepsy gene LGI1 encodes a secreted glycoprotein that binds to the cell surface.</strong> Hum. Molec. Genet. 15: 3436-3445, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17067999/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17067999</a>] [<a href="https://doi.org/10.1093/hmg/ddl421" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17067999">Sirerol-Piquer et al. (2006)</a> showed that the 3 putative N-glycosylation sites of human LGI1 were functional and that glycosylation was required for LGI1 secretion from transfected HEK293T cells. All 7 of the C-terminal EPTP repeats were also required for LGI1 secretion. LGI1 bound to the surface of neurally differentiated rat PC12 cells, and binding reduced the level of activated ERK1/ERK2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17067999" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using immunostaining analysis, <a href="#12" class="mim-tip-reference" title="Hivert, B., Marien, L., Agbam, K. N., Faivre-Sarralh, C. <strong>ADAM22 and ADAM23 modulate the targeting of the Kv1 channel-associated protein LGI1 to the axon initial segment.</strong> J. Cell Sci. 132: jcs219774, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30598502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30598502</a>] [<a href="https://doi.org/10.1242/jcs.219774" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30598502">Hivert et al. (2019)</a> showed that the voltage-gated Kv1 K+ channel (see <a href="/entry/176260">176260</a>)-associated protein Lgi1 was targeted to the axon initial segment (AIS) of cultured rat hippocampal neurons. Lgi1 colocalized with Adam22, but not with Adam23 (<a href="/entry/603710">603710</a>). However, both ADAM proteins appeared to modulate Lgi1 targeting to the AIS. Coexpression analysis in HEK cells revealed that human ADAM22 and ADAM23 were involved in intracellular trafficking of LGI1 and promoted endoplasmic reticulum exit and N-glycan maturation of LGI1. Missense mutations in the EPTP6 domain of LGI1 reduced its interaction with ADAM22 and impaired its recruitment to the AIS. Moreover, Lgi1 and Adam23 colocalized in transport vesicles of rat hippocampal neurons, and Lgi1 likely required coexpression with Adam22 or Adam23 for proper trafficking and axonal transport. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30598502" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#18" class="mim-tip-reference" title="Nobile, C., Michelucci, R., Andreazza, S., Pasini, E., Tosatto, S. C. E., Striano, P. <strong>LGI1 mutations in autosomal dominant and sporadic lateral temporal epilepsy.</strong> Hum. Mutat. 30: 530-536, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19191227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19191227</a>] [<a href="https://doi.org/10.1002/humu.20925" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19191227">Nobile et al. (2009)</a> provided a review of the molecular genetics of the LGI1 gene, noting that 25 different pathogenic mutations had been identified. Most mutations are missense substitutions in both the N-terminal leucine-rich repeat (LRR) and C-terminal EPTP beta-propeller protein domains. No obvious genotype/phenotype correlations were observed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19191227" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By the positional candidate gene approach, <a href="#14" class="mim-tip-reference" title="Kalachikov, S., Evgrafov, O., Ross, B., Winawer, M., Barker-Cummings, C., Boneschi, F. M., Choi, C., Morozov, P., Das, K., Teplitskaya, E., Yu, A., Cayanis, E., Penchaszadeh, G., Kottmann, A. H., Pedley, T. A., Hauser, W. A., Ottman, R., Gilliam, T. C. <strong>Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features.</strong> Nature Genet. 30: 335-341, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11810107/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11810107</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11810107[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/ng832" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11810107">Kalachikov et al. (2002)</a> found that mutations in the LGI1 gene are responsible for autosomal dominant partial epilepsy with auditory features (ADLTE) (ETL1; <a href="/entry/600512">600512</a>). The authors found 5 putative disease mutations in 5 families with this disorder (see, e.g., E383A; <a href="#0001">604619.0001</a>). They showed that the expression pattern of mouse Lgi1 is predominantly neuronal and is consistent with the anatomic regions involved in temporal lobe epilepsy. It was not clear how homozygous loss of a predominantly neuronal gene produces results in glial tumor progression; however, such an effect was considered possible because neurons are known to inhibit glial mitosis, and interactions between neurons and glia appear to regulate homeostasis in both tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11810107" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Morante-Redolat, J. M., Gorostidi-Pagola, A., Piquer-Sirerol, S., Saenz, A., Poza, J. J., Galan, J., Gesk, S., Sarafidou, T., Mautner, V.-F., Binelli, S., Staub, E., Hinzmann, B., and 15 others. <strong>Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy.</strong> Hum. Molec. Genet. 11: 1119-1128, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11978770/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11978770</a>] [<a href="https://doi.org/10.1093/hmg/11.9.1119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11978770">Morante-Redolat et al. (2002)</a> identified 2 truncating mutations (see, e.g., <a href="#0005">604619.0005</a>) in Spanish ADLTE families by direct sequencing. Since several other families with a phenotype consistent with this type of epilepsy lacked identifiable mutations in LGI1, the authors speculated that ADLTE may manifest genetic heterogeneity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11978770" 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="#23" class="mim-tip-reference" title="Sirerol-Piquer, M. S., Ayerdi-Izquierdo, A., Morante-Redolat, J. M., Herranz-Perez, V., Favell, K., Barker, P. A., Perez-Tur, J. <strong>The epilepsy gene LGI1 encodes a secreted glycoprotein that binds to the cell surface.</strong> Hum. Molec. Genet. 15: 3436-3445, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17067999/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17067999</a>] [<a href="https://doi.org/10.1093/hmg/ddl421" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17067999">Sirerol-Piquer et al. (2006)</a> found that all naturally occurring ADLTE-causing mutations in LGI1 that they examined, including both truncating and missense mutations, resulted in retention of LGI1 in the endoplasmic reticulum. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17067999" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Chabrol, E., Popescu, C., Gourfinkel-An, I., Trouillard, O., Depienne, C., Senechal, K., Baulac, M., LeGuern, E., Baulac, S. <strong>Two novel epilepsy-linked mutations leading to a loss of function of LGI1.</strong> Arch. Neurol. 64: 217-222, 2007. Note: Erratum: Arch. Neurol. 64: 657 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17296837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17296837</a>] [<a href="https://doi.org/10.1001/archneur.64.2.217" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17296837">Chabrol et al. (2007)</a> identified 2 respective mutations (<a href="#0008">604619.0008</a>; L232P, <a href="#0009">604619.0009</a>) in a French and an Algerian family with ADLTE. By in vitro studies in Chinese hamster ovary (CHO) and rat adrenal pheochromocytoma cells, they demonstrated that wildtype LGI1 protein, but not E383A or L232P mutant protein, was secreted to the extracellular environment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17296837" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Fanciulli, M., Santulli, L., Errichiello, L., Barozzi, C., Tomasi, L., Rigon, L., Cubeddu, T., de Falco, A., Rampazzo, A., Michelucci, R., Uzzau, S., Striano, S., de Falco, F. A., Striano, P., Nobile, C. <strong>LGI1 microdeletion in autosomal dominant lateral temporal lobe epilepsy.</strong> Neurology 78: 1299-1303, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22496201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22496201</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22496201[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3182518328" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22496201">Fanciulli et al. (2012)</a> identified a heterozygous 81-kb deletion encompassing part of the upstream region and the first 4 exons of the LGI1 gene (<a href="#0012">604619.0012</a>) in affected members of a 3-generation Italian family with classic ADLTE. The deletion was found by CNV analysis after exon sequencing of the gene failed to identify a point mutation. The findings suggested that CNV analysis is a useful diagnostic tool for this disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22496201" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In an analysis of clinical and molecular information from the literature for all 36 published families with ADLTE due to an LGI1 mutation, <a href="#13" class="mim-tip-reference" title="Ho, Y.-Y., Ionita-Laza, I., Ottman, R. <strong>Domain-dependent clustering and genotype-phenotype analysis of LGI1 mutations in ADPEAF.</strong> Neurology 78: 563-568, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22323750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22323750</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22323750[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1212/WNL.0b013e318247ccbf" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22323750">Ho et al. (2012)</a> found that pathogenic mutations clustered significantly more in the N-terminal LRR domains (exons 3-5) compared to the C-terminal EPTP domains (p = 0.026); however, mutations in both domains were clearly pathogenic. Auditory symptoms were less frequent in individuals with truncating mutations in the EPTP domain than in those with other mutation type/domain combinations (58% vs 80%, p = 0.018). The findings provided a basis for understanding the biologic pathways involved in ADLTE. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22323750" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In rat brain, <a href="#21" class="mim-tip-reference" title="Schulte, U., Thumfart, J.-O., Klocker, N., Sailre, C. A., Bildl, W., Biniossek, M., Dehn, D., Deller, T., Eble, S., Abbass, JK., Wangler, T., Knaus, H.-G., Fakler, B. <strong>The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels and inhibits inactivation by Kv-beta-1.</strong> Neuron 49: 697-706, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16504945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16504945</a>] [<a href="https://doi.org/10.1016/j.neuron.2006.01.033" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16504945">Schulte et al. (2006)</a> found that Lgi1 stained prominently in the hippocampal formation, thalamic nuclei, and neocortex. In the hippocampus, Lgi1 was expressed in the outer and middle molecular layers of the dentate gyrus and was tightly associated with Kcna1 (<a href="/entry/176260">176260</a>)-containing channel complexes in presynaptic axon terminals. Functional studies showed that Lgi1 effectively and specifically prevented rapid voltage-gated potassium channel inactivation mediated by the Kv-beta-1 subunit (KCNAB1; <a href="/entry/601141">601141</a>). In other words, Lgi1 effectively upregulates Kcna1 channels. Kcnab1 inactivation was not achieved with mutant Lgi1 proteins, and the loss of function showed a dominant effect in heterozygous coexpression studies with wildtype Lgi1. <a href="#21" class="mim-tip-reference" title="Schulte, U., Thumfart, J.-O., Klocker, N., Sailre, C. A., Bildl, W., Biniossek, M., Dehn, D., Deller, T., Eble, S., Abbass, JK., Wangler, T., Knaus, H.-G., Fakler, B. <strong>The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels and inhibits inactivation by Kv-beta-1.</strong> Neuron 49: 697-706, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16504945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16504945</a>] [<a href="https://doi.org/10.1016/j.neuron.2006.01.033" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16504945">Schulte et al. (2006)</a> suggested that mutations in LGI1 may lead to a complete loss of the Kcnab1-antagonizing effect of presynaptic potassium channels, resulting in increased channel activity and epileptogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16504945" 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 early postnatal wildtype mice, <a href="#26" class="mim-tip-reference" title="Zhou, Y.-D., Lee, S., Jin, Z., Wright, M., Smith, S. E. P., Anderson, M. P. <strong>Arrested maturation of excitatory synapses in autosomal dominant lateral temporal lobe epilepsy.</strong> Nature Med. 15: 1208-1214, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19701204/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19701204</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19701204[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/nm.2019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19701204">Zhou et al. (2009)</a> found that expression of Lgi1 in hippocampus temporally coincided with maturation of presynaptic and postsynaptic functions. Presynaptic maturation was measured by a decrease in presynaptic release probability, whereas postsynaptic maturation was measured by functional changes in NMDA receptor NR2 subunit composition. In contrast, the normal postnatal maturation of presynaptic and postsynaptic function was arrested in a mouse model carrying an Lgi1 truncating mutation (835delC; <a href="#0002">604619.0002</a>), and was magnified in transgenic mice with overexpression of Lgi1. <a href="#26" class="mim-tip-reference" title="Zhou, Y.-D., Lee, S., Jin, Z., Wright, M., Smith, S. E. P., Anderson, M. P. <strong>Arrested maturation of excitatory synapses in autosomal dominant lateral temporal lobe epilepsy.</strong> Nature Med. 15: 1208-1214, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19701204/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19701204</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19701204[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/nm.2019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19701204">Zhou et al. (2009)</a> postulated that Lgi1 acts normally at the presynaptic terminal to overcome KCNAB1-mediated KCNA1 presynaptic channel inhibition during postnatal development, perhaps before KCNAB1 is fully expressed, and lowers presynaptic release probability by upregulating presynaptic KCNA1 channel activity. Mutant truncated Lgi1 was also found to inhibit dendritic pruning, resulting in increased spine density and markedly increased excitatory synaptic transmission in mutant mice. Inhibitory transmission was unaffected. Mutant truncated Lgi1 promoted epileptiform discharge in vitro under partial GABAergic blockade, and caused kindling and decreased threshold for epileptogenesis in mutant mice in vivo, again under partial blockade of GABAergic blockade. <a href="#26" class="mim-tip-reference" title="Zhou, Y.-D., Lee, S., Jin, Z., Wright, M., Smith, S. E. P., Anderson, M. P. <strong>Arrested maturation of excitatory synapses in autosomal dominant lateral temporal lobe epilepsy.</strong> Nature Med. 15: 1208-1214, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19701204/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19701204</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19701204[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/nm.2019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19701204">Zhou et al. (2009)</a> concluded that LGI1 regulates postnatal glutamatergic synapse development, and that mutant LGI1 acts as dominant-negative inhibitor to cause epilepsy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19701204" 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="#25" class="mim-tip-reference" title="Yu, Y. E., Wen, L., Silva, J., Li, Z., Head, K., Sossey-Alaoui, K., Pao, A., Mei, L., Cowell, J. K. <strong>Lgi1 null mutant mice exhibit myoclonic seizures and CA1 neuronal hyperexcitability.</strong> Hum. Molec. Genet. 19: 1702-1711, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20130004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20130004</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20130004[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddq047" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20130004">Yu et al. (2010)</a> reported that Lgi1-null mutant mice showed no gross overall developmental abnormalities on routine histopathologic analysis. After 12 to 18 days of age, the homozygous mutant mice all exhibited myoclonic seizures accompanied by rapid jumping and running, and died shortly thereafter. The heterozygous mutant mice did not develop seizures. Electrophysiologic analysis demonstrated an enhanced excitatory synaptic transmission by increasing the release of the excitatory neurotransmitter glutamate, suggesting a basis for the seizure phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20130004" 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=604619[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<p>In affected members of a family with autosomal dominant partial epilepsy with auditory features (ETL1; <a href="/entry/600512">600512</a>), <a href="#14" class="mim-tip-reference" title="Kalachikov, S., Evgrafov, O., Ross, B., Winawer, M., Barker-Cummings, C., Boneschi, F. M., Choi, C., Morozov, P., Das, K., Teplitskaya, E., Yu, A., Cayanis, E., Penchaszadeh, G., Kottmann, A. H., Pedley, T. A., Hauser, W. A., Ottman, R., Gilliam, T. C. <strong>Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features.</strong> Nature Genet. 30: 335-341, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11810107/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11810107</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11810107[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/ng832" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11810107">Kalachikov et al. (2002)</a> identified a c.1372A-C transversion in exon 8 of the LGI1 gene, resulting in a missense glu383-to-ala (E383A) amino acid substitution in the fourth EAR domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11810107" 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>Variant Function</em></strong></p><p>
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By in vitro functional expression studies, <a href="#4" class="mim-tip-reference" title="Chabrol, E., Popescu, C., Gourfinkel-An, I., Trouillard, O., Depienne, C., Senechal, K., Baulac, M., LeGuern, E., Baulac, S. <strong>Two novel epilepsy-linked mutations leading to a loss of function of LGI1.</strong> Arch. Neurol. 64: 217-222, 2007. Note: Erratum: Arch. Neurol. 64: 657 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17296837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17296837</a>] [<a href="https://doi.org/10.1001/archneur.64.2.217" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17296837">Chabrol et al. (2007)</a> demonstrated that the E383A mutant protein was not secreted into the culture medium, suggesting that a loss of function underlies pathogenesis of ADLTE. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17296837" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In affected members of a family with autosomal dominant partial epilepsy with auditory features (ETL1; <a href="/entry/600512">600512</a>), <a href="#14" class="mim-tip-reference" title="Kalachikov, S., Evgrafov, O., Ross, B., Winawer, M., Barker-Cummings, C., Boneschi, F. M., Choi, C., Morozov, P., Das, K., Teplitskaya, E., Yu, A., Cayanis, E., Penchaszadeh, G., Kottmann, A. H., Pedley, T. A., Hauser, W. A., Ottman, R., Gilliam, T. C. <strong>Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features.</strong> Nature Genet. 30: 335-341, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11810107/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11810107</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11810107[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/ng832" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11810107">Kalachikov et al. (2002)</a> found a 1-bp deletion, c.835delC, in exon 6 of the LGI1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11810107" 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>Variant Function</em></strong></p><p>
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By in vitro functional expression studies, <a href="#22" class="mim-tip-reference" title="Senechal, K. R., Thaller, C., Noebels, J. L. <strong>ADPEAF mutations reduce levels of secreted LGI1, a putative tumor suppressor protein linked to epilepsy.</strong> Hum. Molec. Genet. 14: 1613-1620, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15857855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15857855</a>] [<a href="https://doi.org/10.1093/hmg/ddi169" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15857855">Senechal et al. (2005)</a> showed that the c.835delC-equivalent mutation in mouse Lgi1 resulted in decreased levels of secreted protein, indicating a loss-of-function mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15857855" 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">rs1589762127 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1589762127;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=rs1589762127" 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=rs1589762127" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In affected members of a family with autosomal dominant partial epilepsy with auditory features (ETL1; <a href="/entry/600512">600512</a>), <a href="#14" class="mim-tip-reference" title="Kalachikov, S., Evgrafov, O., Ross, B., Winawer, M., Barker-Cummings, C., Boneschi, F. M., Choi, C., Morozov, P., Das, K., Teplitskaya, E., Yu, A., Cayanis, E., Penchaszadeh, G., Kottmann, A. H., Pedley, T. A., Hauser, W. A., Ottman, R., Gilliam, T. C. <strong>Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features.</strong> Nature Genet. 30: 335-341, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11810107/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11810107</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11810107[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/ng832" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11810107">Kalachikov et al. (2002)</a> found a single nucleotide change, from C to A, at the third base from the acceptor intron-exon junction of exon 4. It was possible to show that a portion of the mRNA transcript had retention of the entire intron 3 as a result of the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11810107" 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">rs104894166 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894166;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=rs104894166" 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=rs104894166" 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=RCV000005766 OR RCV003595853" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005766, RCV003595853" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005766...</a>
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<p>In a large Norwegian family with autosomal dominant lateral temporal lobe epilepsy (ETL1; <a href="/entry/600512">600512</a>) characterized by aphasic seizures, <a href="#10" class="mim-tip-reference" title="Gu, W., Brodtkorb, E., Steinlein, O. K. <strong>LGI1 is mutated in familial temporal lobe epilepsy characterized by aphasic seizures.</strong> Ann. Neurol. 52: 364-367, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12205652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12205652</a>] [<a href="https://doi.org/10.1002/ana.10280" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12205652">Gu et al. (2002)</a> identified a cys46-to-arg substitution (C46R) in a conserved extracellular cysteine cluster region of the LGI1 gene. The authors noted that the conserved cysteine clusters likely form disulfide bonds important in a structural role of the protein. Mutation in the LGI1 gene may alter neuronal migration in the developing nervous system which would result in subtle lesions causing epilepsy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12205652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In an Italian family with autosomal dominant partial epilepsy with auditory features, <a href="#19" class="mim-tip-reference" title="Pizzuti, A., Flex, E., Di Bonaventura, C., Dottorini, T., Egeo, G., Manfredi, M., Dallapiccola, B., Giallonardo, A. T. <strong>Epilepsy with auditory features: a LGI1 gene mutation suggests a loss-of-function mechanism.</strong> Ann. Neurol. 53: 396-399, 2003. Note: Erratum: Ann. Neurol. 54: 137 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12601709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12601709</a>] [<a href="https://doi.org/10.1002/ana.10492" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12601709">Pizzuti et al. (2003)</a> identified a heterozygous change in the LGI1 gene, resulting in the C46R substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12601709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs797044998 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs797044998;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/rs797044998?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=rs797044998" 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=rs797044998" 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=RCV000193378 OR RCV003595878" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000193378, RCV003595878" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000193378...</a>
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<p>In a 2-generation family with autosomal dominant lateral temporal lobe epilepsy (ETL1; <a href="/entry/600512">600512</a>), <a href="#17" class="mim-tip-reference" title="Morante-Redolat, J. M., Gorostidi-Pagola, A., Piquer-Sirerol, S., Saenz, A., Poza, J. J., Galan, J., Gesk, S., Sarafidou, T., Mautner, V.-F., Binelli, S., Staub, E., Hinzmann, B., and 15 others. <strong>Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy.</strong> Hum. Molec. Genet. 11: 1119-1128, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11978770/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11978770</a>] [<a href="https://doi.org/10.1093/hmg/11.9.1119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11978770">Morante-Redolat et al. (2002)</a> reported a c.1320C-T transition in exon 8 of LGI1 in affected family members. The mutation was predicted to generate a premature stop codon, eliminating the last 80 amino acids of the 557 amino-acid protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11978770" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with sporadic ETL1, <a href="#3" class="mim-tip-reference" title="Bisulli, F., Tinuper, P., Scudellaro, E., Naldi, I., Bagattin, A., Avoni, P., Michelucci, R., Nobile, C. <strong>A de novo LGI1 mutation in sporadic partial epilepsy with auditory features.</strong> Ann. Neurol. 56: 455-456, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15349881/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15349881</a>] [<a href="https://doi.org/10.1002/ana.20218" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15349881">Bisulli et al. (2004)</a> identified the c.1320C-T transition, which they termed c.1420C-T, as a de novo mutation. They suggested that the mutation was likely to be transmitted to the patient's offspring in an autosomal dominant pattern. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15349881" 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">rs28939075 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28939075;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=rs28939075" 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=rs28939075" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p><a href="#7" class="mim-tip-reference" title="Fertig, E., Lincoln, A., Martinuzzi, A., Mattson, R. H., Hisama, F. M. <strong>Novel LGI1 mutation in a family with autosomal dominant partial epilepsy with auditory features.</strong> Neurology 60: 1687-1690, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12771268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12771268</a>] [<a href="https://doi.org/10.1212/01.wnl.0000063324.39980.4a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12771268">Fertig et al. (2003)</a> reported a large American family of Italian descent with autosomal dominant partial epilepsy with auditory features (ETL1; <a href="/entry/600512">600512</a>) with multiple affected members over 4 generations. Seven affected members and 1 unaffected member had a heterozygous c.953T-G transversion in exon 8 of the LGI1 gene, resulting in a phe318-to-cys (F318C) substitution. Mean age of onset was 25 years, and all patients reported an auditory aura preceding a secondary generalized seizure. The authors noted that the mutation occurred in the first EAR domain in the C terminus of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12771268" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a French father and daughter with autosomal dominant lateral temporal lobe epilepsy with auditory features (ETL1; <a href="/entry/600512">600512</a>), <a href="#4" class="mim-tip-reference" title="Chabrol, E., Popescu, C., Gourfinkel-An, I., Trouillard, O., Depienne, C., Senechal, K., Baulac, M., LeGuern, E., Baulac, S. <strong>Two novel epilepsy-linked mutations leading to a loss of function of LGI1.</strong> Arch. Neurol. 64: 217-222, 2007. Note: Erratum: Arch. Neurol. 64: 657 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17296837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17296837</a>] [<a href="https://doi.org/10.1001/archneur.64.2.217" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17296837">Chabrol et al. (2007)</a> identified a heterozygous G-to-A transition in intron 5 of the LGI1 gene (c.431+1G-A), resulting in the skipping of exons 3 and 4 and a protein predicted to lack 48 amino acids, suggesting a loss of function, although haploinsufficiency could not be ruled out. Two sibs of the daughter, 1 of whom was affected and 1 of whom may have been affected, had severe depression and committed suicide. The daughter also had severe depression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17296837" 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">rs104894167 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894167;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=rs104894167" 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=rs104894167" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 3 members of an Algerian family with autosomal dominant lateral temporal lobe epilepsy with auditory features (ETL1; <a href="/entry/600512">600512</a>), <a href="#4" class="mim-tip-reference" title="Chabrol, E., Popescu, C., Gourfinkel-An, I., Trouillard, O., Depienne, C., Senechal, K., Baulac, M., LeGuern, E., Baulac, S. <strong>Two novel epilepsy-linked mutations leading to a loss of function of LGI1.</strong> Arch. Neurol. 64: 217-222, 2007. Note: Erratum: Arch. Neurol. 64: 657 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17296837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17296837</a>] [<a href="https://doi.org/10.1001/archneur.64.2.217" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17296837">Chabrol et al. (2007)</a> identified a heterozygous c.695T-C transition in exon 7 of the LGI1 gene, resulting in a leu232-to-pro (L232P) substitution in the second EAR domain. In vitro functional expression studies showed that the L232P mutant protein was not secreted into the culture medium, suggesting a loss of function underlies the pathogenesis of ADLTE. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17296837" 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">rs119488099 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119488099;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=rs119488099" 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=rs119488099" 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=RCV000005771 OR RCV000188042 OR RCV002227996 OR RCV003407283" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005771, RCV000188042, RCV002227996, RCV003407283" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005771...</a>
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<p>In a 36-year-old woman with lateral temporal lobe epilepsy (ETL1; <a href="/entry/600512">600512</a>) manifest as telephone-induced seizures, <a href="#16" class="mim-tip-reference" title="Michelucci, R., Mecarelli, O., Bovo, G., Bisulli, F., Testoni, S., Striano, P., Striano, S., Tinuper, P., Nobile, C. <strong>A de novo LGI1 mutation causing idiopathic partial epilepsy with telephone-induced seizures.</strong> Neurology 68: 2150-2151, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17562837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17562837</a>] [<a href="https://doi.org/10.1212/01.wnl.0000264932.44153.3c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17562837">Michelucci et al. (2007)</a> identified a de novo heterozygous c.406C-T transition in exon 4, resulting in an arg136-to-trp (R136W) substitution. The patient had an 11-year history of recurrent partial complex and secondarily generalized seizures evoked almost exclusively by answering the telephone. Other auditory stimuli could also elicit seizures. The seizures were accompanied by distortion or attenuation of sound, inability to understand language, and inability to speak appropriately, all consistent with lateral temporal lobe involvement. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17562837" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0011 EPILEPSY, FAMILIAL TEMPORAL LOBE, 1</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs119488100 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119488100;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=rs119488100" 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=rs119488100" 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=RCV000005772" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005772" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005772</a>
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<p>In affected members of a Italian family with autosomal dominant lateral temporal lobe epilepsy (ETL1; <a href="/entry/600512">600512</a>), <a href="#24" class="mim-tip-reference" title="Striano, P., de Falco, A., Diani, E., Bovo, G., Furlan, S., Vitiello, L., Pinardi, F., Striano, S., Michelucci, R., de Falco, F. A., Nobile, C. <strong>A novel loss-of-function LGI1 mutation linked to autosomal dominant lateral temporal epilepsy.</strong> Arch. Neurol. 65: 939-942, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18625862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18625862</a>] [<a href="https://doi.org/10.1001/archneur.65.7.939" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18625862">Striano et al. (2008)</a> identified a heterozygous c.365T-A transversion in exon 4 of the LGI1 gene, resulting in an ile122-to-lys (I122K) substitution in a highly conserved residue. The affected residue is part of the hydrophobic core of the second leucine-rich repeat and is important for proper protein folding. In vitro functional expression studies in cultured HEK293 cells followed by western blot analysis showed that the mutant protein was translated but not secreted. <a href="#24" class="mim-tip-reference" title="Striano, P., de Falco, A., Diani, E., Bovo, G., Furlan, S., Vitiello, L., Pinardi, F., Striano, S., Michelucci, R., de Falco, F. A., Nobile, C. <strong>A novel loss-of-function LGI1 mutation linked to autosomal dominant lateral temporal epilepsy.</strong> Arch. Neurol. 65: 939-942, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18625862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18625862</a>] [<a href="https://doi.org/10.1001/archneur.65.7.939" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18625862">Striano et al. (2008)</a> noted that the findings were consistent with LGI1 functioning as an extracellular ligand. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18625862" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0012 EPILEPSY, FAMILIAL TEMPORAL LOBE, 1</strong>
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LGI1, 81-KB DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000194261" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000194261" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000194261</a>
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<p>In affected members of a 3-generation Italian family with autosomal dominant lateral temporal lobe epilepsy (ETL1; <a href="/entry/600512">600512</a>), <a href="#6" class="mim-tip-reference" title="Fanciulli, M., Santulli, L., Errichiello, L., Barozzi, C., Tomasi, L., Rigon, L., Cubeddu, T., de Falco, A., Rampazzo, A., Michelucci, R., Uzzau, S., Striano, S., de Falco, F. A., Striano, P., Nobile, C. <strong>LGI1 microdeletion in autosomal dominant lateral temporal lobe epilepsy.</strong> Neurology 78: 1299-1303, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22496201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22496201</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22496201[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3182518328" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22496201">Fanciulli et al. (2012)</a> identified a heterozygous 81-kb deletion encompassing part of the upstream region and the first 4 exons of the LGI1 gene, predicted to result in a loss of function. The deletion was found by CNV analysis after exon sequencing of the gene failed to identify a point mutation. The deletion was not found in several large databases. There were 8 affected individuals. Most patients had onset of seizures in the second decade, although 2 had onset as adults. Six had tonic-clonic seizures with focal onset, and most experienced accompanying auditory features. Brain imaging was unremarkable in all patients who were studied, and EEG showed mild abnormalities only in 3 patients. Patients showed a good response to antiepileptic medication. Two unaffected family members, aged 24 and 17 years, also carried the deletion, consistent with later onset of the disorder or incomplete penetrance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22496201" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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<a id="Anderson2010" class="mim-anchor"></a>
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Anderson, M. P.
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<strong>Arrested glutamatergic synapse development in human partial epilepsy.</strong>
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Epilepsy Curr. 10: 153-158, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21157544/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21157544</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21157544" 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.1535-7511.2010.01386.x" target="_blank">Full Text</a>]
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Bigner, S. H., Vogelstein, B.
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<strong>Cytogenetics and molecular genetics of malignant gliomas and medulloblastoma.</strong>
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Brain Path. 1: 12-18, 1990.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1669688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1669688</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1669688" 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.1750-3639.1990.tb00633.x" target="_blank">Full Text</a>]
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Bisulli, F., Tinuper, P., Scudellaro, E., Naldi, I., Bagattin, A., Avoni, P., Michelucci, R., Nobile, C.
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<strong>A de novo LGI1 mutation in sporadic partial epilepsy with auditory features.</strong>
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Ann. Neurol. 56: 455-456, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15349881/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15349881</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15349881" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.20218" target="_blank">Full Text</a>]
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Chabrol, E., Popescu, C., Gourfinkel-An, I., Trouillard, O., Depienne, C., Senechal, K., Baulac, M., LeGuern, E., Baulac, S.
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<strong>Two novel epilepsy-linked mutations leading to a loss of function of LGI1.</strong>
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Arch. Neurol. 64: 217-222, 2007. Note: Erratum: Arch. Neurol. 64: 657 only, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17296837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17296837</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17296837" 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/10.1001/archneur.64.2.217" target="_blank">Full Text</a>]
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Chernova, O. B., Somerville, R. P. T., Cowell, J. K.
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<strong>A novel gene, LGI1, from 10q24 is rearranged and downregulated in malignant brain tumors.</strong>
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Oncogene 17: 2873-2881, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9879993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9879993</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9879993" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/sj.onc.1202481" target="_blank">Full Text</a>]
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<strong>LGI1 microdeletion in autosomal dominant lateral temporal lobe epilepsy.</strong>
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[<a href="https://doi.org/10.1212/WNL.0b013e3182518328" target="_blank">Full Text</a>]
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<strong>Novel LGI1 mutation in a family with autosomal dominant partial epilepsy with auditory features.</strong>
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[<a href="https://doi.org/10.1212/01.wnl.0000063324.39980.4a" target="_blank">Full Text</a>]
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<strong>Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission.</strong>
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Science 313: 1792-1795, 2006.
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[<a href="https://doi.org/10.1126/science.1129947" target="_blank">Full Text</a>]
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<strong>LGI1: a gene involved in epileptogenesis and glioma progression?</strong>
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[<a href="https://doi.org/10.1007/s10048-005-0216-5" target="_blank">Full Text</a>]
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Gu, W., Brodtkorb, E., Steinlein, O. K.
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<strong>LGI1 is mutated in familial temporal lobe epilepsy characterized by aphasic seizures.</strong>
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Ann. Neurol. 52: 364-367, 2002.
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[<a href="https://doi.org/10.1002/ana.10280" target="_blank">Full Text</a>]
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Gu, W., Wevers, A., Schroder, H., Grzeschik, K.-H., Derst, C., Brodtkorb, E., de Vos, R., Steinlein, O. K.
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<strong>The LGI1 gene involved in lateral temporal lobe epilepsy belongs to a new subfamily of leucine-rich repeat proteins.</strong>
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FEBS Lett. 519: 71-76, 2002.
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[<a href="https://doi.org/10.1016/s0014-5793(02)02713-8" target="_blank">Full Text</a>]
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Hivert, B., Marien, L., Agbam, K. N., Faivre-Sarralh, C.
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<strong>ADAM22 and ADAM23 modulate the targeting of the Kv1 channel-associated protein LGI1 to the axon initial segment.</strong>
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J. Cell Sci. 132: jcs219774, 2019.
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[<a href="https://doi.org/10.1242/jcs.219774" target="_blank">Full Text</a>]
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Ho, Y.-Y., Ionita-Laza, I., Ottman, R.
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<strong>Domain-dependent clustering and genotype-phenotype analysis of LGI1 mutations in ADPEAF.</strong>
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Neurology 78: 563-568, 2012.
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[<a href="https://doi.org/10.1212/WNL.0b013e318247ccbf" target="_blank">Full Text</a>]
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Kalachikov, S., Evgrafov, O., Ross, B., Winawer, M., Barker-Cummings, C., Boneschi, F. M., Choi, C., Morozov, P., Das, K., Teplitskaya, E., Yu, A., Cayanis, E., Penchaszadeh, G., Kottmann, A. H., Pedley, T. A., Hauser, W. A., Ottman, R., Gilliam, T. C.
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<strong>Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features.</strong>
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Nature Genet. 30: 335-341, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11810107/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11810107</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11810107[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=11810107" 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/ng832" target="_blank">Full Text</a>]
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<a id="Kunapuli2004" class="mim-anchor"></a>
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<div class="">
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Kunapuli, P., Kasyapa, C. S., Hawthorn, L., Cowell, J. K.
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<strong>LGI1, a putative tumor metastasis suppressor gene, controls in vitro invasiveness and expression of matrix metalloproteinases in glioma cells through the ERK1/2 pathway.</strong>
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[<a href="https://doi.org/10.1074/jbc.M314192200" target="_blank">Full Text</a>]
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<a id="Michelucci2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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<strong>A de novo LGI1 mutation causing idiopathic partial epilepsy with telephone-induced seizures.</strong>
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Neurology 68: 2150-2151, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17562837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17562837</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17562837" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/01.wnl.0000264932.44153.3c" target="_blank">Full Text</a>]
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<a id="17" class="mim-anchor"></a>
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<a id="Morante-Redolat2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Morante-Redolat, J. M., Gorostidi-Pagola, A., Piquer-Sirerol, S., Saenz, A., Poza, J. J., Galan, J., Gesk, S., Sarafidou, T., Mautner, V.-F., Binelli, S., Staub, E., Hinzmann, B., and 15 others.
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<strong>Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy.</strong>
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Hum. Molec. Genet. 11: 1119-1128, 2002.
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[<a href="https://doi.org/10.1093/hmg/11.9.1119" target="_blank">Full Text</a>]
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<a id="Nobile2009" class="mim-anchor"></a>
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<div class="">
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Nobile, C., Michelucci, R., Andreazza, S., Pasini, E., Tosatto, S. C. E., Striano, P.
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<strong>LGI1 mutations in autosomal dominant and sporadic lateral temporal epilepsy.</strong>
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[<a href="https://doi.org/10.1002/humu.20925" target="_blank">Full Text</a>]
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<a id="Pizzuti2003" class="mim-anchor"></a>
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<div class="">
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<strong>Epilepsy with auditory features: a LGI1 gene mutation suggests a loss-of-function mechanism.</strong>
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Ann. Neurol. 53: 396-399, 2003. Note: Erratum: Ann. Neurol. 54: 137 only, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12601709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12601709</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12601709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.10492" target="_blank">Full Text</a>]
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<a id="Scheel2002" class="mim-anchor"></a>
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<strong>A common protein interaction domain links two recently identified epilepsy genes.</strong>
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[<a href="https://doi.org/10.1093/hmg/11.15.1757" target="_blank">Full Text</a>]
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<strong>The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels and inhibits inactivation by Kv-beta-1.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16504945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16504945</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16504945" 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.neuron.2006.01.033" 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="22" class="mim-anchor"></a>
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<a id="Senechal2005" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
|
Senechal, K. R., Thaller, C., Noebels, J. L.
|
|
<strong>ADPEAF mutations reduce levels of secreted LGI1, a putative tumor suppressor protein linked to epilepsy.</strong>
|
|
Hum. Molec. Genet. 14: 1613-1620, 2005.
|
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|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15857855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15857855</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15857855" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddi169" 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="23" class="mim-anchor"></a>
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<a id="Sirerol-Piquer2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sirerol-Piquer, M. S., Ayerdi-Izquierdo, A., Morante-Redolat, J. M., Herranz-Perez, V., Favell, K., Barker, P. A., Perez-Tur, J.
|
|
<strong>The epilepsy gene LGI1 encodes a secreted glycoprotein that binds to the cell surface.</strong>
|
|
Hum. Molec. Genet. 15: 3436-3445, 2006.
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|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17067999/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17067999</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17067999" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddl421" 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="24" class="mim-anchor"></a>
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<a id="Striano2008" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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|
Striano, P., de Falco, A., Diani, E., Bovo, G., Furlan, S., Vitiello, L., Pinardi, F., Striano, S., Michelucci, R., de Falco, F. A., Nobile, C.
|
|
<strong>A novel loss-of-function LGI1 mutation linked to autosomal dominant lateral temporal epilepsy.</strong>
|
|
Arch. Neurol. 65: 939-942, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18625862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18625862</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18625862" 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/10.1001/archneur.65.7.939" 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="25" class="mim-anchor"></a>
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<a id="Yu2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yu, Y. E., Wen, L., Silva, J., Li, Z., Head, K., Sossey-Alaoui, K., Pao, A., Mei, L., Cowell, J. K.
|
|
<strong>Lgi1 null mutant mice exhibit myoclonic seizures and CA1 neuronal hyperexcitability.</strong>
|
|
Hum. Molec. Genet. 19: 1702-1711, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20130004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20130004</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20130004[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=20130004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddq047" 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="26" class="mim-anchor"></a>
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<a id="Zhou2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhou, Y.-D., Lee, S., Jin, Z., Wright, M., Smith, S. E. P., Anderson, M. P.
|
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<strong>Arrested maturation of excitatory synapses in autosomal dominant lateral temporal lobe epilepsy.</strong>
|
|
Nature Med. 15: 1208-1214, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19701204/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19701204</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19701204[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=19701204" 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/nm.2019" 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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Bao Lige - updated : 03/02/2022
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</span>
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</div>
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</div>
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<div class="row collapse" id="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">
|
|
Patricia A. Hartz - updated : 03/15/2013<br>Cassandra L. Kniffin - updated : 2/21/2013<br>Cassandra L. Kniffin - updated : 10/23/2012<br>George E. Tiller - updated : 12/1/2011<br>Cassandra L. Kniffin - updated : 1/19/2011<br>Cassandra L. Kniffin - updated : 11/13/2009<br>Cassandra L. Kniffin - updated : 10/16/2008<br>George E. Tiller - updated : 6/16/2008<br>Cassandra L. Kniffin - updated : 12/17/2007<br>Cassandra L. Kniffin - updated : 10/3/2007<br>Ada Hamosh - updated : 1/25/2007<br>Patricia A. Hartz - updated : 12/13/2006<br>Cassandra L. Kniffin - updated : 11/16/2005<br>Cassandra L. Kniffin - updated : 1/4/2005<br>Patricia A. Hartz - updated : 12/1/2003<br>Cassandra L. Kniffin - updated : 8/12/2003<br>George E. Tiller - updated : 6/19/2003<br>Cassandra L. Kniffin - updated : 5/7/2003<br>George E. Tiller - updated : 12/18/2002<br>Cassandra L. Kniffin - updated : 11/13/2002<br>Victor A. McKusick - updated : 1/29/2002
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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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Wilson H. Y. Lo : 2/26/2000
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="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 : 12/02/2024
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</span>
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</div>
|
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</div>
|
|
<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">
|
|
mgross : 03/02/2022<br>carol : 09/30/2016<br>mgross : 03/15/2013<br>carol : 3/8/2013<br>ckniffin : 2/21/2013<br>carol : 10/24/2012<br>ckniffin : 10/23/2012<br>alopez : 12/5/2011<br>terry : 12/1/2011<br>wwang : 2/3/2011<br>ckniffin : 1/19/2011<br>wwang : 11/17/2009<br>ckniffin : 11/13/2009<br>wwang : 10/17/2008<br>ckniffin : 10/16/2008<br>wwang : 6/20/2008<br>terry : 6/16/2008<br>carol : 2/29/2008<br>wwang : 2/1/2008<br>ckniffin : 12/17/2007<br>wwang : 10/9/2007<br>wwang : 10/3/2007<br>ckniffin : 10/3/2007<br>mgross : 10/2/2007<br>alopez : 1/26/2007<br>terry : 1/25/2007<br>wwang : 12/20/2006<br>terry : 12/13/2006<br>wwang : 11/22/2005<br>ckniffin : 11/16/2005<br>tkritzer : 1/12/2005<br>ckniffin : 1/4/2005<br>mgross : 12/1/2003<br>cwells : 8/20/2003<br>ckniffin : 8/12/2003<br>tkritzer : 7/30/2003<br>ckniffin : 7/28/2003<br>cwells : 6/19/2003<br>carol : 5/16/2003<br>ckniffin : 5/7/2003<br>ckniffin : 5/7/2003<br>cwells : 12/18/2002<br>carol : 11/20/2002<br>ckniffin : 11/13/2002<br>ckniffin : 11/13/2002<br>alopez : 3/12/2002<br>alopez : 1/29/2002<br>terry : 1/29/2002<br>terry : 6/4/2001<br>mcapotos : 7/31/2000<br>carol : 2/28/2000<br>carol : 2/28/2000
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
|
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<span class="mim-font">
|
|
<strong>*</strong> 604619
|
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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>
|
|
<span class="mim-font">
|
|
|
|
LEUCINE-RICH GENE, GLIOMA-INACTIVATED, 1; LGI1
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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">
|
|
<em>Alternative titles; symbols</em>
|
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</span>
|
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</p>
|
|
</div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
EPITEMPIN; EPTP
|
|
</span>
|
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</h4>
|
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</div>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: LGI1</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>
|
|
<span class="mim-text-font">
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|
|
<strong>SNOMEDCT:</strong> 784377008;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: 10q23.33
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 10:93,757,936-93,798,159 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
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<br />
|
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</div>
|
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<div>
|
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<h4>
|
|
<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
|
|
</th>
|
|
<th>
|
|
Phenotype
|
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</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
10q23.33
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Epilepsy, familial temporal lobe, 1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
600512
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
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|
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</tr>
|
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|
|
</tbody>
|
|
</table>
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</div>
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</div>
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<div>
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<br />
|
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The LGI1 gene encodes a secreted leucine-rich protein that is expressed in brain and plays a role in regulating postnatal glutamatergic synapse development (summary by Anderson, 2010). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<span class="mim-text-font">
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<p>Chernova et al. (1998) used a positional cloning strategy to isolate LGI1, which they found was rearranged as a result of a t(10;19)(q24;q13) balanced translocation in a glioblastoma (137800) cell line (T98G). The LGI1 cDNA predicts a precursor protein with 557 amino acids and a calculated molecular mass of 64 kD. After the cleavage of the signal peptide, the mature LGI1 protein is 60 kD. The protein contains a hydrophobic segment representing a putative transmembrane domain, with the amino terminus located outside the cell. It also contains 3.5 leucine-rich repeats (LRR) with conserved cysteine-rich flanking sequences. In the LRR domain, LGI1 shows high homology with a number of transmembrane and extracellular proteins that function as receptors and adhesion proteins. LGI1 is predominantly expressed in neural tissues, especially in brain; its expression is reduced in low-grade brain tumors and significantly reduced or absent in malignant gliomas. </p><p>Morante-Redolat et al. (2002) reported alternative splicing of exon 8, which appeared to vary between brain and skeletal muscle. </p><p>Most genes mutated in hereditary idiopathic epilepsies encode subunits of ion channels. Two apparent exceptions to this rule are the MASS1 gene (GPR98; 602851), which is mutated in the Frings mouse model of audiogenic epilepsy, and LGI1. Scheel et al. (2002) determined by amino acid analysis of both proteins that each contains a novel homology domain consisting of 7 repeats, each consisting of a 44-residue EAR (epilepsy-associated repeat) domain. The architecture and structural features of the EAR domain make it a likely member of the growing class of protein interaction domains with a 7-bladed beta-propeller fold. In the MASS1 gene product, which is a fragment of the very large G protein-coupled receptor VLGR1, the EAR domain is part of the ligand-binding ectodomain. LGI1, as well as a number of newly identified LGI1 relatives, is predicted to be a secreted protein, and consists of an N-terminal leucine-rich repeat region and a C-terminal EAR region. The human genome encodes at least 6 EAR proteins, some of which map to chromosomal regions associated with seizure disorders. Scheel et al. (2002) hypothesized that the EAR domain may play an important role in the pathogenesis of epilepsy, either by binding to an unknown antiepileptic ligand or by interfering with axon guidance or synaptogenesis. </p><p>Sirerol-Piquer et al. (2006) referred to the 7 tandem repeats of the LGI1 EAR domain as EPTP repeats. They reported that LGI1 also has 3 putative N-glycosylation sites. </p><p>Senechal et al. (2005) showed that Lgi1 was secreted in transfected 293T cells. In situ hybridization of adult mouse brain showed that Lgi1 mRNA is intensely expressed in granule cells of the dentate gyrus and the CA3-CA1 pyramidal cell layer of the hippocampus, with diffuse staining of the neocortex and other brain regions. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Nobile et al. (2009) noted that the LGI1 gene contains 8 exons spanning 39.6 kb. </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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<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>Chernova et al. (1998) mapped the LGI1 gene to chromosome 10q24. Nobile et al. (2009) stated that the LGI1 gene maps to chromosome 10q23.33. </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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<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>Chernova et al. (1998) found that the LGI1 gene was rearranged as a result of a t(10;19)(q24;q13) balanced translocation in a glioblastoma (137800) cell line (T98G). They suggested that the localization of LGI1 to the 10q24 region and its rearrangement or inactivation in malignant brain tumors make it a strong candidate tumor suppressor gene involved in the malignant progression of glial tumors. The study was performed because previous studies had found that loss of 1 copy of chromosome 10 is a common event in high-grade gliomas; rearrangement and loss of at least some parts of the second copy, especially in the 10q23-q26 region, had been demonstrated in approximately 80% of glioblastoma multiforme tumors (Bigner and Vogelstein, 1990). Chernova et al. (1998) also detected rearrangement of the LGI1 gene in the A172 glioblastoma cell line and several glioblastoma tumors, resulting in complete absence of LGI1 expression. </p><p>By semiquantitative PCR, Gu et al. (2002) detected expression of LGI1 in all tissues examined, with highest expression in brain. Immunolocalization revealed LGI1-immunoreactive neurons in all layers of the frontal and temporal cortex, with strongest labeling in layers II/III. Most of the labeled neurons displayed a pyramidal shape. Staining was detected within the perikaryon and occasionally in apical and basal dendrites, but not in nuclei. Similar labeling was found in all cortices investigated, but the intensities showed slight variations. The T98G glioblastoma cell line shows loss of LGI1 expression, and reexpression of LGI1 inhibits proliferation, invasiveness, and anchorage-independent growth. </p><p>Using gene expression arrays, Kunapuli et al. (2004) showed that forced reexpression of LGI1 in T98G cells resulted in downregulation of several metalloproteases, in particular MMP1 (120353) and MMP3 (185250). LGI1 expression also resulted in inhibition of ERK1 (MAPK3; 601795) and ERK2 (MAPK1; 176948) phosphorylation, but not p38 (MAPK14; 600289) phosphorylation. Kunapuli et al. (2004) concluded that LGI1 plays a major role in suppressing production of metalloproteases through the ERK signaling pathway. </p><p>Gu et al. (2005) provided a detailed review of the LGI1 gene and concluded that the evidence supporting its role in malignant gliomas is weak. </p><p>Fukata et al. (2006) showed that ADAM22 (603709) serves as a receptor for LGI1. LGI1 enhances AMPA receptor-mediated synaptic transmission in hippocampal slices. The mutated form of LGI1 failed to bind to ADAM22. ADAM22 is anchored in the postsynaptic density by cytoskeletal scaffolds containing stargazin (602911). Fukata et al. (2006) found that the interaction of ADAM22 and LGI1 with PSD95 (602887) was specific, as PSD95 and LGI1 quantitatively coimmunoprecipitated with ADAM22. Because PSD95 controls synaptic AMPA receptor number, Fukata et al. (2006) asked whether application of LGI1 to hippocampal slices would influence glutaminergic transmission. Incubation of hippocampal slices in LGI1-AP media significantly increased the synaptic AMPA/NMDA ratio; nontagged LGI1 showed a similar effect. Fukata et al. (2006) concluded that their study established a neuronal ligand-receptor interaction between LGI1 and ADAM22, both of which are genetically related to epilepsy. This study also identified LGI1 as an extracellular factor that controls synaptic strength at the excitatory synapses. Stargazin controls the trafficking and gating of AMPA receptors,0j and PSD95 anchors the AMPA receptor/stargazin complex at postsynaptic sites. Because the ADAM22 and stargazin binding sites on PSD95 do not overlap, the LGI1/ADAM22 complex may stabilize the AMPA receptor/stargazin complex on the PSD95 scaffolding platform. </p><p>Using mutation analysis, Sirerol-Piquer et al. (2006) showed that the 3 putative N-glycosylation sites of human LGI1 were functional and that glycosylation was required for LGI1 secretion from transfected HEK293T cells. All 7 of the C-terminal EPTP repeats were also required for LGI1 secretion. LGI1 bound to the surface of neurally differentiated rat PC12 cells, and binding reduced the level of activated ERK1/ERK2. </p><p>Using immunostaining analysis, Hivert et al. (2019) showed that the voltage-gated Kv1 K+ channel (see 176260)-associated protein Lgi1 was targeted to the axon initial segment (AIS) of cultured rat hippocampal neurons. Lgi1 colocalized with Adam22, but not with Adam23 (603710). However, both ADAM proteins appeared to modulate Lgi1 targeting to the AIS. Coexpression analysis in HEK cells revealed that human ADAM22 and ADAM23 were involved in intracellular trafficking of LGI1 and promoted endoplasmic reticulum exit and N-glycan maturation of LGI1. Missense mutations in the EPTP6 domain of LGI1 reduced its interaction with ADAM22 and impaired its recruitment to the AIS. Moreover, Lgi1 and Adam23 colocalized in transport vesicles of rat hippocampal neurons, and Lgi1 likely required coexpression with Adam22 or Adam23 for proper trafficking and axonal transport. </p>
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</span>
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<div>
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</div>
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<div>
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<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>Nobile et al. (2009) provided a review of the molecular genetics of the LGI1 gene, noting that 25 different pathogenic mutations had been identified. Most mutations are missense substitutions in both the N-terminal leucine-rich repeat (LRR) and C-terminal EPTP beta-propeller protein domains. No obvious genotype/phenotype correlations were observed. </p><p>By the positional candidate gene approach, Kalachikov et al. (2002) found that mutations in the LGI1 gene are responsible for autosomal dominant partial epilepsy with auditory features (ADLTE) (ETL1; 600512). The authors found 5 putative disease mutations in 5 families with this disorder (see, e.g., E383A; 604619.0001). They showed that the expression pattern of mouse Lgi1 is predominantly neuronal and is consistent with the anatomic regions involved in temporal lobe epilepsy. It was not clear how homozygous loss of a predominantly neuronal gene produces results in glial tumor progression; however, such an effect was considered possible because neurons are known to inhibit glial mitosis, and interactions between neurons and glia appear to regulate homeostasis in both tissues. </p><p>Morante-Redolat et al. (2002) identified 2 truncating mutations (see, e.g., 604619.0005) in Spanish ADLTE families by direct sequencing. Since several other families with a phenotype consistent with this type of epilepsy lacked identifiable mutations in LGI1, the authors speculated that ADLTE may manifest genetic heterogeneity. </p><p>Sirerol-Piquer et al. (2006) found that all naturally occurring ADLTE-causing mutations in LGI1 that they examined, including both truncating and missense mutations, resulted in retention of LGI1 in the endoplasmic reticulum. </p><p>Chabrol et al. (2007) identified 2 respective mutations (604619.0008; L232P, 604619.0009) in a French and an Algerian family with ADLTE. By in vitro studies in Chinese hamster ovary (CHO) and rat adrenal pheochromocytoma cells, they demonstrated that wildtype LGI1 protein, but not E383A or L232P mutant protein, was secreted to the extracellular environment. </p><p>Fanciulli et al. (2012) identified a heterozygous 81-kb deletion encompassing part of the upstream region and the first 4 exons of the LGI1 gene (604619.0012) in affected members of a 3-generation Italian family with classic ADLTE. The deletion was found by CNV analysis after exon sequencing of the gene failed to identify a point mutation. The findings suggested that CNV analysis is a useful diagnostic tool for this disorder. </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>Genotype/Phenotype Correlations</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In an analysis of clinical and molecular information from the literature for all 36 published families with ADLTE due to an LGI1 mutation, Ho et al. (2012) found that pathogenic mutations clustered significantly more in the N-terminal LRR domains (exons 3-5) compared to the C-terminal EPTP domains (p = 0.026); however, mutations in both domains were clearly pathogenic. Auditory symptoms were less frequent in individuals with truncating mutations in the EPTP domain than in those with other mutation type/domain combinations (58% vs 80%, p = 0.018). The findings provided a basis for understanding the biologic pathways involved in ADLTE. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In rat brain, Schulte et al. (2006) found that Lgi1 stained prominently in the hippocampal formation, thalamic nuclei, and neocortex. In the hippocampus, Lgi1 was expressed in the outer and middle molecular layers of the dentate gyrus and was tightly associated with Kcna1 (176260)-containing channel complexes in presynaptic axon terminals. Functional studies showed that Lgi1 effectively and specifically prevented rapid voltage-gated potassium channel inactivation mediated by the Kv-beta-1 subunit (KCNAB1; 601141). In other words, Lgi1 effectively upregulates Kcna1 channels. Kcnab1 inactivation was not achieved with mutant Lgi1 proteins, and the loss of function showed a dominant effect in heterozygous coexpression studies with wildtype Lgi1. Schulte et al. (2006) suggested that mutations in LGI1 may lead to a complete loss of the Kcnab1-antagonizing effect of presynaptic potassium channels, resulting in increased channel activity and epileptogenesis. </p><p>In early postnatal wildtype mice, Zhou et al. (2009) found that expression of Lgi1 in hippocampus temporally coincided with maturation of presynaptic and postsynaptic functions. Presynaptic maturation was measured by a decrease in presynaptic release probability, whereas postsynaptic maturation was measured by functional changes in NMDA receptor NR2 subunit composition. In contrast, the normal postnatal maturation of presynaptic and postsynaptic function was arrested in a mouse model carrying an Lgi1 truncating mutation (835delC; 604619.0002), and was magnified in transgenic mice with overexpression of Lgi1. Zhou et al. (2009) postulated that Lgi1 acts normally at the presynaptic terminal to overcome KCNAB1-mediated KCNA1 presynaptic channel inhibition during postnatal development, perhaps before KCNAB1 is fully expressed, and lowers presynaptic release probability by upregulating presynaptic KCNA1 channel activity. Mutant truncated Lgi1 was also found to inhibit dendritic pruning, resulting in increased spine density and markedly increased excitatory synaptic transmission in mutant mice. Inhibitory transmission was unaffected. Mutant truncated Lgi1 promoted epileptiform discharge in vitro under partial GABAergic blockade, and caused kindling and decreased threshold for epileptogenesis in mutant mice in vivo, again under partial blockade of GABAergic blockade. Zhou et al. (2009) concluded that LGI1 regulates postnatal glutamatergic synapse development, and that mutant LGI1 acts as dominant-negative inhibitor to cause epilepsy. </p><p>Yu et al. (2010) reported that Lgi1-null mutant mice showed no gross overall developmental abnormalities on routine histopathologic analysis. After 12 to 18 days of age, the homozygous mutant mice all exhibited myoclonic seizures accompanied by rapid jumping and running, and died shortly thereafter. The heterozygous mutant mice did not develop seizures. Electrophysiologic analysis demonstrated an enhanced excitatory synaptic transmission by increasing the release of the excitatory neurotransmitter glutamate, suggesting a basis for the seizure phenotype. </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>12 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 EPILEPSY, FAMILIAL TEMPORAL LOBE, 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LGI1, GLU383ALA
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<br />
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SNP: rs28937874,
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ClinVar: RCV000005763
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a family with autosomal dominant partial epilepsy with auditory features (ETL1; 600512), Kalachikov et al. (2002) identified a c.1372A-C transversion in exon 8 of the LGI1 gene, resulting in a missense glu383-to-ala (E383A) amino acid substitution in the fourth EAR domain. </p><p><strong><em>Variant Function</em></strong></p><p>
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By in vitro functional expression studies, Chabrol et al. (2007) demonstrated that the E383A mutant protein was not secreted into the culture medium, suggesting that a loss of function underlies pathogenesis of ADLTE. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 EPILEPSY, FAMILIAL TEMPORAL LOBE, 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LGI1, 1-BP DEL, 835C
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<br />
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ClinVar: RCV000005764
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a family with autosomal dominant partial epilepsy with auditory features (ETL1; 600512), Kalachikov et al. (2002) found a 1-bp deletion, c.835delC, in exon 6 of the LGI1 gene. </p><p><strong><em>Variant Function</em></strong></p><p>
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By in vitro functional expression studies, Senechal et al. (2005) showed that the c.835delC-equivalent mutation in mouse Lgi1 resulted in decreased levels of secreted protein, indicating a loss-of-function mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 EPILEPSY, FAMILIAL TEMPORAL LOBE, 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LGI1, IVS3AS, C-A, -3
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<br />
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SNP: rs1589762127,
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ClinVar: RCV000005765
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a family with autosomal dominant partial epilepsy with auditory features (ETL1; 600512), Kalachikov et al. (2002) found a single nucleotide change, from C to A, at the third base from the acceptor intron-exon junction of exon 4. It was possible to show that a portion of the mRNA transcript had retention of the entire intron 3 as a result of the mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 EPILEPSY, FAMILIAL TEMPORAL LOBE, 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LGI1, CYS46ARG
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<br />
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SNP: rs104894166,
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ClinVar: RCV000005766, RCV003595853
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a large Norwegian family with autosomal dominant lateral temporal lobe epilepsy (ETL1; 600512) characterized by aphasic seizures, Gu et al. (2002) identified a cys46-to-arg substitution (C46R) in a conserved extracellular cysteine cluster region of the LGI1 gene. The authors noted that the conserved cysteine clusters likely form disulfide bonds important in a structural role of the protein. Mutation in the LGI1 gene may alter neuronal migration in the developing nervous system which would result in subtle lesions causing epilepsy. </p><p>In an Italian family with autosomal dominant partial epilepsy with auditory features, Pizzuti et al. (2003) identified a heterozygous change in the LGI1 gene, resulting in the C46R substitution. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 EPILEPSY, FAMILIAL TEMPORAL LOBE, 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LGI1, 1320C-T
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<br />
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SNP: rs797044998,
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gnomAD: rs797044998,
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ClinVar: RCV000193378, RCV003595878
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a 2-generation family with autosomal dominant lateral temporal lobe epilepsy (ETL1; 600512), Morante-Redolat et al. (2002) reported a c.1320C-T transition in exon 8 of LGI1 in affected family members. The mutation was predicted to generate a premature stop codon, eliminating the last 80 amino acids of the 557 amino-acid protein. </p><p>In a patient with sporadic ETL1, Bisulli et al. (2004) identified the c.1320C-T transition, which they termed c.1420C-T, as a de novo mutation. They suggested that the mutation was likely to be transmitted to the patient's offspring in an autosomal dominant pattern. </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-text-font">
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<strong>.0006 MOVED TO 604619.0004</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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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0007 EPILEPSY, FAMILIAL TEMPORAL LOBE, 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LGI1, PHE318CYS
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<br />
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SNP: rs28939075,
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ClinVar: RCV000005768
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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>Fertig et al. (2003) reported a large American family of Italian descent with autosomal dominant partial epilepsy with auditory features (ETL1; 600512) with multiple affected members over 4 generations. Seven affected members and 1 unaffected member had a heterozygous c.953T-G transversion in exon 8 of the LGI1 gene, resulting in a phe318-to-cys (F318C) substitution. Mean age of onset was 25 years, and all patients reported an auditory aura preceding a secondary generalized seizure. The authors noted that the mutation occurred in the first EAR domain in the C terminus of the protein. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0008 EPILEPSY, FAMILIAL TEMPORAL LOBE, 1</strong>
|
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</span>
|
|
</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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LGI1, IVS5DS, G-A, +1
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<br />
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SNP: rs2134001459,
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ClinVar: RCV000005769, RCV004700190
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a French father and daughter with autosomal dominant lateral temporal lobe epilepsy with auditory features (ETL1; 600512), Chabrol et al. (2007) identified a heterozygous G-to-A transition in intron 5 of the LGI1 gene (c.431+1G-A), resulting in the skipping of exons 3 and 4 and a protein predicted to lack 48 amino acids, suggesting a loss of function, although haploinsufficiency could not be ruled out. Two sibs of the daughter, 1 of whom was affected and 1 of whom may have been affected, had severe depression and committed suicide. The daughter also had severe depression. </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>.0009 EPILEPSY, FAMILIAL TEMPORAL LOBE, 1</strong>
|
|
</span>
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|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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LGI1, LEU232PRO
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<br />
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SNP: rs104894167,
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ClinVar: RCV000005770
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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 3 members of an Algerian family with autosomal dominant lateral temporal lobe epilepsy with auditory features (ETL1; 600512), Chabrol et al. (2007) identified a heterozygous c.695T-C transition in exon 7 of the LGI1 gene, resulting in a leu232-to-pro (L232P) substitution in the second EAR domain. In vitro functional expression studies showed that the L232P mutant protein was not secreted into the culture medium, suggesting a loss of function underlies the pathogenesis of ADLTE. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 EPILEPSY, FAMILIAL TEMPORAL LOBE, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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LGI1, ARG136TRP
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<br />
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SNP: rs119488099,
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ClinVar: RCV000005771, RCV000188042, RCV002227996, RCV003407283
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 36-year-old woman with lateral temporal lobe epilepsy (ETL1; 600512) manifest as telephone-induced seizures, Michelucci et al. (2007) identified a de novo heterozygous c.406C-T transition in exon 4, resulting in an arg136-to-trp (R136W) substitution. The patient had an 11-year history of recurrent partial complex and secondarily generalized seizures evoked almost exclusively by answering the telephone. Other auditory stimuli could also elicit seizures. The seizures were accompanied by distortion or attenuation of sound, inability to understand language, and inability to speak appropriately, all consistent with lateral temporal lobe involvement. </p>
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|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 EPILEPSY, FAMILIAL TEMPORAL LOBE, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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LGI1, ILE122LYS
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<br />
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SNP: rs119488100,
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ClinVar: RCV000005772
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</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a Italian family with autosomal dominant lateral temporal lobe epilepsy (ETL1; 600512), Striano et al. (2008) identified a heterozygous c.365T-A transversion in exon 4 of the LGI1 gene, resulting in an ile122-to-lys (I122K) substitution in a highly conserved residue. The affected residue is part of the hydrophobic core of the second leucine-rich repeat and is important for proper protein folding. In vitro functional expression studies in cultured HEK293 cells followed by western blot analysis showed that the mutant protein was translated but not secreted. Striano et al. (2008) noted that the findings were consistent with LGI1 functioning as an extracellular ligand. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 EPILEPSY, FAMILIAL TEMPORAL LOBE, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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LGI1, 81-KB DEL
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<br />
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ClinVar: RCV000194261
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</span>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In affected members of a 3-generation Italian family with autosomal dominant lateral temporal lobe epilepsy (ETL1; 600512), Fanciulli et al. (2012) identified a heterozygous 81-kb deletion encompassing part of the upstream region and the first 4 exons of the LGI1 gene, predicted to result in a loss of function. The deletion was found by CNV analysis after exon sequencing of the gene failed to identify a point mutation. The deletion was not found in several large databases. There were 8 affected individuals. Most patients had onset of seizures in the second decade, although 2 had onset as adults. Six had tonic-clonic seizures with focal onset, and most experienced accompanying auditory features. Brain imaging was unremarkable in all patients who were studied, and EEG showed mild abnormalities only in 3 patients. Patients showed a good response to antiepileptic medication. Two unaffected family members, aged 24 and 17 years, also carried the deletion, consistent with later onset of the disorder or incomplete penetrance. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
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</h4>
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<div>
|
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<p />
|
|
</div>
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<div>
|
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<ol>
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<li>
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<p class="mim-text-font">
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Anderson, M. P.
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<p class="mim-text-font">
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Bigner, S. H., Vogelstein, B.
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<strong>Cytogenetics and molecular genetics of malignant gliomas and medulloblastoma.</strong>
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Bisulli, F., Tinuper, P., Scudellaro, E., Naldi, I., Bagattin, A., Avoni, P., Michelucci, R., Nobile, C.
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<strong>A de novo LGI1 mutation in sporadic partial epilepsy with auditory features.</strong>
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Chabrol, E., Popescu, C., Gourfinkel-An, I., Trouillard, O., Depienne, C., Senechal, K., Baulac, M., LeGuern, E., Baulac, S.
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Arch. Neurol. 64: 217-222, 2007. Note: Erratum: Arch. Neurol. 64: 657 only, 2007.
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[PubMed: 17296837]
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<p class="mim-text-font">
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Chernova, O. B., Somerville, R. P. T., Cowell, J. K.
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<strong>A novel gene, LGI1, from 10q24 is rearranged and downregulated in malignant brain tumors.</strong>
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Oncogene 17: 2873-2881, 1998.
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[PubMed: 9879993]
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Fanciulli, M., Santulli, L., Errichiello, L., Barozzi, C., Tomasi, L., Rigon, L., Cubeddu, T., de Falco, A., Rampazzo, A., Michelucci, R., Uzzau, S., Striano, S., de Falco, F. A., Striano, P., Nobile, C.
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<strong>LGI1 microdeletion in autosomal dominant lateral temporal lobe epilepsy.</strong>
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[PubMed: 22496201]
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[Full Text: https://doi.org/10.1212/WNL.0b013e3182518328]
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Fertig, E., Lincoln, A., Martinuzzi, A., Mattson, R. H., Hisama, F. M.
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<strong>Novel LGI1 mutation in a family with autosomal dominant partial epilepsy with auditory features.</strong>
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Neurology 60: 1687-1690, 2003.
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[PubMed: 12771268]
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[Full Text: https://doi.org/10.1212/01.wnl.0000063324.39980.4a]
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</p>
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<li>
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<p class="mim-text-font">
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Fukata, Y., Adesnik, H., Iwanaga, T., Bredt, D. S., Nicoll, R. A., Fukata, M.
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<strong>Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission.</strong>
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Science 313: 1792-1795, 2006.
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[PubMed: 16990550]
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[Full Text: https://doi.org/10.1126/science.1129947]
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</p>
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<li>
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<p class="mim-text-font">
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Gu, W., Brodtkorb, E., Piepoli, T., Finocchiaro, G., Steinlein, O. K.
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<strong>LGI1: a gene involved in epileptogenesis and glioma progression?</strong>
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Neurogenetics 6: 59-66, 2005.
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[PubMed: 15827762]
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<li>
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<p class="mim-text-font">
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Gu, W., Brodtkorb, E., Steinlein, O. K.
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<strong>LGI1 is mutated in familial temporal lobe epilepsy characterized by aphasic seizures.</strong>
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Ann. Neurol. 52: 364-367, 2002.
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[PubMed: 12205652]
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[Full Text: https://doi.org/10.1002/ana.10280]
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</p>
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<li>
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<p class="mim-text-font">
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Gu, W., Wevers, A., Schroder, H., Grzeschik, K.-H., Derst, C., Brodtkorb, E., de Vos, R., Steinlein, O. K.
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<strong>The LGI1 gene involved in lateral temporal lobe epilepsy belongs to a new subfamily of leucine-rich repeat proteins.</strong>
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FEBS Lett. 519: 71-76, 2002.
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[PubMed: 12023020]
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[Full Text: https://doi.org/10.1016/s0014-5793(02)02713-8]
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</p>
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<li>
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<p class="mim-text-font">
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|
Hivert, B., Marien, L., Agbam, K. N., Faivre-Sarralh, C.
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<strong>ADAM22 and ADAM23 modulate the targeting of the Kv1 channel-associated protein LGI1 to the axon initial segment.</strong>
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J. Cell Sci. 132: jcs219774, 2019.
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[PubMed: 30598502]
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[Full Text: https://doi.org/10.1242/jcs.219774]
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</p>
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<li>
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<p class="mim-text-font">
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|
Ho, Y.-Y., Ionita-Laza, I., Ottman, R.
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<strong>Domain-dependent clustering and genotype-phenotype analysis of LGI1 mutations in ADPEAF.</strong>
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|
Neurology 78: 563-568, 2012.
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[PubMed: 22323750]
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[Full Text: https://doi.org/10.1212/WNL.0b013e318247ccbf]
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</p>
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</li>
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<li>
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|
<p class="mim-text-font">
|
|
Kalachikov, S., Evgrafov, O., Ross, B., Winawer, M., Barker-Cummings, C., Boneschi, F. M., Choi, C., Morozov, P., Das, K., Teplitskaya, E., Yu, A., Cayanis, E., Penchaszadeh, G., Kottmann, A. H., Pedley, T. A., Hauser, W. A., Ottman, R., Gilliam, T. C.
|
|
<strong>Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features.</strong>
|
|
Nature Genet. 30: 335-341, 2002.
|
|
|
|
|
|
[PubMed: 11810107]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng832]
|
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|
|
</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Kunapuli, P., Kasyapa, C. S., Hawthorn, L., Cowell, J. K.
|
|
<strong>LGI1, a putative tumor metastasis suppressor gene, controls in vitro invasiveness and expression of matrix metalloproteinases in glioma cells through the ERK1/2 pathway.</strong>
|
|
J. Biol. Chem. 279: 23151-23157, 2004. Note: Erratum: J. Biol. Chem. 282: 2752 only, 2007.
|
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|
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|
|
[PubMed: 15047712]
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|
|
[Full Text: https://doi.org/10.1074/jbc.M314192200]
|
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Michelucci, R., Mecarelli, O., Bovo, G., Bisulli, F., Testoni, S., Striano, P., Striano, S., Tinuper, P., Nobile, C.
|
|
<strong>A de novo LGI1 mutation causing idiopathic partial epilepsy with telephone-induced seizures.</strong>
|
|
Neurology 68: 2150-2151, 2007.
|
|
|
|
|
|
[PubMed: 17562837]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000264932.44153.3c]
|
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</p>
|
|
</li>
|
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<li>
|
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<p class="mim-text-font">
|
|
Morante-Redolat, J. M., Gorostidi-Pagola, A., Piquer-Sirerol, S., Saenz, A., Poza, J. J., Galan, J., Gesk, S., Sarafidou, T., Mautner, V.-F., Binelli, S., Staub, E., Hinzmann, B., and 15 others.
|
|
<strong>Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy.</strong>
|
|
Hum. Molec. Genet. 11: 1119-1128, 2002.
|
|
|
|
|
|
[PubMed: 11978770]
|
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|
|
[Full Text: https://doi.org/10.1093/hmg/11.9.1119]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Nobile, C., Michelucci, R., Andreazza, S., Pasini, E., Tosatto, S. C. E., Striano, P.
|
|
<strong>LGI1 mutations in autosomal dominant and sporadic lateral temporal epilepsy.</strong>
|
|
Hum. Mutat. 30: 530-536, 2009.
|
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|
|
|
|
[PubMed: 19191227]
|
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[Full Text: https://doi.org/10.1002/humu.20925]
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Pizzuti, A., Flex, E., Di Bonaventura, C., Dottorini, T., Egeo, G., Manfredi, M., Dallapiccola, B., Giallonardo, A. T.
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<strong>Epilepsy with auditory features: a LGI1 gene mutation suggests a loss-of-function mechanism.</strong>
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Ann. Neurol. 53: 396-399, 2003. Note: Erratum: Ann. Neurol. 54: 137 only, 2003.
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[PubMed: 12601709]
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[Full Text: https://doi.org/10.1002/ana.10492]
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Scheel, H., Tomiuk, S., Hofmann, K.
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<strong>A common protein interaction domain links two recently identified epilepsy genes.</strong>
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Hum. Molec. Genet. 11: 1757-1762, 2002.
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[PubMed: 12095917]
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[Full Text: https://doi.org/10.1093/hmg/11.15.1757]
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Schulte, U., Thumfart, J.-O., Klocker, N., Sailre, C. A., Bildl, W., Biniossek, M., Dehn, D., Deller, T., Eble, S., Abbass, JK., Wangler, T., Knaus, H.-G., Fakler, B.
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<strong>The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels and inhibits inactivation by Kv-beta-1.</strong>
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Neuron 49: 697-706, 2006.
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[PubMed: 16504945]
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[Full Text: https://doi.org/10.1016/j.neuron.2006.01.033]
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Senechal, K. R., Thaller, C., Noebels, J. L.
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<strong>ADPEAF mutations reduce levels of secreted LGI1, a putative tumor suppressor protein linked to epilepsy.</strong>
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Hum. Molec. Genet. 14: 1613-1620, 2005.
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[PubMed: 15857855]
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[Full Text: https://doi.org/10.1093/hmg/ddi169]
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Sirerol-Piquer, M. S., Ayerdi-Izquierdo, A., Morante-Redolat, J. M., Herranz-Perez, V., Favell, K., Barker, P. A., Perez-Tur, J.
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<strong>The epilepsy gene LGI1 encodes a secreted glycoprotein that binds to the cell surface.</strong>
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Hum. Molec. Genet. 15: 3436-3445, 2006.
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[PubMed: 17067999]
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[Full Text: https://doi.org/10.1093/hmg/ddl421]
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Striano, P., de Falco, A., Diani, E., Bovo, G., Furlan, S., Vitiello, L., Pinardi, F., Striano, S., Michelucci, R., de Falco, F. A., Nobile, C.
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<strong>A novel loss-of-function LGI1 mutation linked to autosomal dominant lateral temporal epilepsy.</strong>
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Yu, Y. E., Wen, L., Silva, J., Li, Z., Head, K., Sossey-Alaoui, K., Pao, A., Mei, L., Cowell, J. K.
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<strong>Lgi1 null mutant mice exhibit myoclonic seizures and CA1 neuronal hyperexcitability.</strong>
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Hum. Molec. Genet. 19: 1702-1711, 2010.
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[PubMed: 20130004]
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[Full Text: https://doi.org/10.1093/hmg/ddq047]
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Zhou, Y.-D., Lee, S., Jin, Z., Wright, M., Smith, S. E. P., Anderson, M. P.
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<strong>Arrested maturation of excitatory synapses in autosomal dominant lateral temporal lobe epilepsy.</strong>
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[Full Text: https://doi.org/10.1038/nm.2019]
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Bao Lige - updated : 03/02/2022<br>Patricia A. Hartz - updated : 03/15/2013<br>Cassandra L. Kniffin - updated : 2/21/2013<br>Cassandra L. Kniffin - updated : 10/23/2012<br>George E. Tiller - updated : 12/1/2011<br>Cassandra L. Kniffin - updated : 1/19/2011<br>Cassandra L. Kniffin - updated : 11/13/2009<br>Cassandra L. Kniffin - updated : 10/16/2008<br>George E. Tiller - updated : 6/16/2008<br>Cassandra L. Kniffin - updated : 12/17/2007<br>Cassandra L. Kniffin - updated : 10/3/2007<br>Ada Hamosh - updated : 1/25/2007<br>Patricia A. Hartz - updated : 12/13/2006<br>Cassandra L. Kniffin - updated : 11/16/2005<br>Cassandra L. Kniffin - updated : 1/4/2005<br>Patricia A. Hartz - updated : 12/1/2003<br>Cassandra L. Kniffin - updated : 8/12/2003<br>George E. Tiller - updated : 6/19/2003<br>Cassandra L. Kniffin - updated : 5/7/2003<br>George E. Tiller - updated : 12/18/2002<br>Cassandra L. Kniffin - updated : 11/13/2002<br>Victor A. McKusick - updated : 1/29/2002
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